Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.56589036
The KSHV 5 cyclin was also found to associate weakly with cdk 4 . 0.56589036^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.76714702
Activation of CDK 4 is regulated , in part , by its association with a D type cyclin . 0.76714702^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.60977768
The formation of complexes and enzymatic activity of cyclin D CDK 4 and cyclin D CDK 6 kinases is negatively regulated by p16INK4 ( MTS1 / CDK4I / CDKN2 ) via its specific interaction with CDK 4 and CDK 6 catalytic subunits . 0.60977768^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.50876416
Moreover , when it is ectopically overexpressed in mammalian cells , cyclin D 1 ( T156A ) assembles with CDK 4 in the cytoplasm but is not imported into the cell nucleus . 0.50876416^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.62074279
In young adult rat liver after 70 % partial hepatectomy , the association of cyclin D 1 with cdk 4 was significantly promoted during G 1 phase and was maximal at 18 hr , corresponding mainly to late G 1 . 0.62074279^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.51351556
Likewise , cyclin D is complexed with its catalytic partners CDK 4 and CDK 6 in senescent HDF , but it is not known whether these complexes are active . p21Sdi1 , Cip 1 , Waf 1 , a ubiquitous inhibitor of the activity of cyclin CDK complexes , increases progressively throughout the life span of HDF , but then declines again after the cells become senescent . 0.51351556^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.86132617
Protein binding and REF assays showed that the region of the cyclin box required for the interaction with CDK 4 as well as C terminal sequences determining protein stability were crucial for transformation . 0.86132617^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.55231035
The detection of complexes containing cyclin D 3 , cdk 4 , p 21 , and PCNA suggests that cdk 4 , along with PCNA , may get sequestered into high order structures held together by pRb and cyclin D 3 . 0.55231035^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.59725919
RESULTS : Viral K cyclin interacted with cyclin dependent kinases cdk 2 , cdk 4 , and cdk 6 and with the cyclin / cdk inhibitory proteins p21Cip1 and p27Kip1 in BC 3 cell lysates . 0.59725919^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :1.2102371
K cyclin activates cellular cyclin dependent kinases ( CDK ) 4 and 6 , generating enzymes with a substrate selectivity deviant from CDK 4 and CDK 6 activated by D type cyclins , suggesting different biochemical and biological functions . 1.2102371^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cyclin dependent kinase 4 ( CDK 4 ) regulates progression through the G 1 phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
MTS 1 encodes p 16 , an inhibitor of cyclin dependent kinase 4 ( cdk 4 ) which complexes with cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Activation of cyclin dependent kinase 4 ( cdk 4 ) by mouse MO 15 associated kinase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Role of the cyclin dependent kinase 4 and 6 inhibitor gene family p 15 , p 16 , p 18 and p 19 in leukemia and lymphoma . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Stimulation of the estrogen receptor by cyclin D 1 is independent of cyclin dependent kinase 4 activation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 ( Cdk 4 ) activity is misregulated in most cancers . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mutation of p 16 , p 21 or cyclin dependent kinase 4 is rare in acute lymphoblastic leukaemia . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Rescue by cyclin D 1 was enhanced by c myc but not by cyclin E and was reversed by infecting cyclin D 1 reconstituted cells with a retroviral vector encoding catalytically inactive cyclin dependent kinase 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The mechanism by which cyclin dependent kinase 4 ( CDK 4 ) regulates cell cycle progression is not entirely clear . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have found that cyclin D 1 is expressed in STSP arrested G 1 fibroblasts but not in low serum arrested G 0 fibroblasts , whereas cyclin dependent kinase 4 ( cdk 4 ) and proliferating cell nuclear antigen ( PCNA ) are equivalently expressed under conditions of both STSP treatment and serum deprivation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The p16Ink4 / MTS1 / CDKN2 is a cell cycle regulatory inhibitor of cyclin dependent kinase 4 ( cdk 4 ) , and a candidate tumour suppressor whose gene on chromosome band 9p21 is frequently deleted or mutated in diverse types of cancer . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDKN 2 encodes a M ( r ) 16 , 000 protein ( p 16 ) that plays a key role in cell cycle control by binding to the cyclin dependent kinase 4 enzyme and inhibiting its ability to phosphorylate critical substrates necessary for transition past the G 1 phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Suppression of cyclin dependent kinase 4 during induced differentiation of erythroleukemia cells . ^^^ Here we show that HMBA causes a rapid decrease in the level of cyclin dependent kinase 4 ( cdk 4 ) protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclic AMP induced G 1 phase arrest mediated by an inhibitor ( p27Kip1 ) of cyclin dependent kinase 4 activation . ^^^ Complexes between cyclin D 1 and cyclin dependent kinase 4 ( cdk 4 ) assemble in growth arrested cells , but cdk 4 is not phosphorylated in vivo by the cdk activating kinase ( CAK ) and remains inactive . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The oncoprotein cyclin D 1 binds to and activates cyclin dependent kinase 4 ( cdk 4 ) , whose activity is inhibited by p16INK4 , the product of the putative tumor suppressor gene MTS 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Lysis of rodent fibroblasts , mouse macrophages , or myeloid cells with Tween 20 followed by precipitation with antibodies to cyclins D 1 , D 2 , and D 3 or to their major catalytic partner , cyclin dependent kinase 4 ( cdk 4 ) , yielded kinase activities in immune complexes which readily phosphorylated the retinoblastoma protein ( pRb ) but not histone H 1 or casein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The accumulation of assembled holoenzymes composed of regulatory D type cyclins and their catalytic partner , cyclin dependent kinase 4 ( cdk 4 ) , is rate limiting for progression through the G 1 phase of the cell cycle in mammalian fibroblasts . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Representative mAbs were useful for immunoblotting and detected D type cyclins coprecipitating in complexes recovered with antiserum to cyclin dependent kinase 4 ( CDK 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We examined the expression of the cyclin dependent kinase 4 , p34PSK J3 / cdk4 protein , in small dense , activated , and proliferating primary B lymphocytes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDKN2 / p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated . p 16 is involved in a cell cycle regulatory cascade that includes cyclin dependent kinase 4 ( cdk 4 ) , cyclin D 1 , and pRb ( retinoblastoma ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Association of cyclin dependent kinase 4 and cyclin D 1 in neonatal beta cells after mitogenic stimulation by lysophosphatidic acid . ^^^ The presence of cyclin dependent kinase 4 and an association with a catalytic partner cyclin D 1 , a process by which the progression through the cell cycle is regulated in other cell types , was shown to follow this . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 ( CDK 4 ) and CDK 6 and control cellular proliferation by preventing entry into the S phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here we demonstrate that treatment of breast carcinoma MCF 7 cells with PGA 2 leads to G 1 arrest associated with a dramatic decrease in the levels of cyclin D 1 and cyclin dependent kinase 4 ( cdk 4 ) and accompanied by an increase in the expression of p 21 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , cyclin D 3 mRNA appears early in G 1 , remains constant in stimulated cells , but accumulates in unstimulated arrested cells , paralleling the cyclin dependent kinase 4 mRNA expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We report here that these cells also have a 3 fold increase in the duration of G 1 , lower levels of cyclin D 1 protein , and a marked decrease in retinoblastoma kinase activity associated with cyclin dependent kinase 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Recently , p16 / MTS1 was isolated from 9p21 22 as a multiple tumor suppressor gene , which regulates the cyclin dependent kinase 4 in the G1 / S phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Following surface IgM ( sIgM ) cross linking on mature B cells , we observed increased expression of the early G 1 kinase , cyclin dependent kinase 4 ( cdk 4 ) , and one of its regulatory subunits , cyclin D 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D type cyclins are involved in regulation of cell traverse through G 1 primarily by activating the cyclin dependent kinase 4 ( CDK 4 ) and targeting it to the retinoblastoma tumour suppressor protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Malignant astrocytomas with homozygous CDKN2 / p16 gene deletions have higher Ki 67 proliferation indices . p 16 is involved in a cell cycle regulatory cascade that includes cyclin dependent kinase 4 ( cdk 4 ) , cyclin D 1 and pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TGF beta 1 induced alterations in other cell cycle regulatory molecules , cyclin dependent kinase 4 , cyclin D 1 , pRB , and p27Kip1 , occurred late and were dispensable in some of the sensitive cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mouse p 16 , which is an inhibitor of cyclin dependent kinase 4 , may suppress the cancer development in mouse hepatocarcinogenesis , or suppress liver cell immortalization . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Inhibition of retinoblastoma protein phosphorylation by myogenesis induced changes in the subunit composition of the cyclin dependent kinase 4 complex . ^^^ Upon C2C12 myogenesis , the level of the cyclin dependent kinase 4 ( CDK 4 ) protein does not change , but its Rb kinase activity is down regulated markedly . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The decrease of pRB mRNA is blocked by cycloheximide , suggesting the requirement of ongoing protein synthesis . p21ras expression leads also to decreases of c myc and tissue metalloproteinase inhibitor 2 mRNAs , whereas cyclin dependent kinase 4 , cyclin D 1 , E2F 1 , and ornithine decarboxylase are unaffected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Concurrent overexpression of cyclin D 1 and cyclin dependent kinase 4 ( Cdk 4 ) in intestinal adenomas from multiple intestinal neoplasia ( Min ) mice and human familial adenomatous polyposis patients . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
It was hypothesized that cyclin dependent kinase 4 , cdk 4 , might be a critical target enzyme to affect the related events of c myc transcription and progression through G 1 phase of the cell cycle within cells transformed by p 210 BCR ABL , and further , that cdk 4 might be downregulated by cAMP to inhibit proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cell cycle of mesangial cells was evaluated by measurement of [ 3H ] thymidine incorporation , flow cytometry , and cyclin dependent kinase 4 kinase assay . ^^^ AxCAp 16 and AxCAp 21 also inhibited the mitogen induced increase in cyclin dependent kinase 4 kinase activity and reduced the percentage of cells in S phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes : retinoblastoma protein , cyclin dependent kinase 2 , and cyclin dependent kinase 4 as molecular targets . ^^^ The induction of cyclin D 2 and the decrease in p 27 were not inhibited by UP , whereas the induction of cyclin E , cyclin A , cyclin dependent kinase 2 , and cyclin dependent kinase 4 was strongly inhibited , potentially explaining the inhibition of retinoblastoma protein phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The ability to revert the transformed phenotype of these cells with antisense cyclin D 1 suggests that cyclin D 1 or its associated cyclin dependent kinase 4 may be useful targets in the therapy of colon cancer . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Decreased transforming growth factor beta type 2 receptor expression in intestinal adenomas from Min / + mice is associated with increased cyclin D 1 and cyclin dependent kinase 4 expression . ^^^ To evaluate the expression of TGF beta RII in premalignant intestinal adenomas and the relationship with cell cycle regulation , we investigated the expression of TGF beta RII , cyclin D 1 , and cyclin dependent kinase 4 ( Cdk 4 ) in Min / + mouse intestinal adenomas . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To explain this paradoxic effect , we investigated the effects of bFGF on cyclins and protein members of cyclin complexes that exert positive and negative control on the progression of cells through the G 1 phase of the cell cycle . bFGF induced an increase in cyclin D 1 , cyclin E , and cyclin dependent kinase 4 ( cdk 4 ) protein levels in a bFGF dose dependent manner . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 are not down regulated in L 929 cells after addition of glucocorticoids , and the abundance of cyclin D / Cdk4 complexes does not change . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
There were no significant differences in the expression of c fos , c jun , c myc , cyclin D 2 , D 3 , cyclin dependent kinase 2 , cyclin dependent kinase 4 , and p 21 among the clones . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Histone H 1 kinase activity was increased significantly in p 13 ( suc 1 ) precipitates of apoptotic PC 12 cells , which was due to increased activation and / or expression of cdc 2 kinase . ( 2 ) The protein levels of cyclin dependent kinase 4 , cyclin D , and proliferating cell nuclear antigen that are normally expressed in the cell cycle were increased during neuronal PC 12 cell apoptosis . ( 3 ) The levels of the catalytic subunit , but not the regulatory subunit of the calcium / calmodulin dependent protein phosphatase 2B , decreased significantly concomitant with a significant decrease in protein phosphatase 2B activity early in the apoptotic process . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Effects of exogenous p16INK4a on growth of cells with various status of cell cycle regulators . p16INK4a , a protein that inhibits cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , is deficient in many human cancers and in established lines of tumor cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclin D 1 , cyclin dependent kinase 4 , and cyclin E proteins , however , decreased in association with RA mediated G 1 arrest . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The known cyclin D 3 partner , cyclin dependent kinase 4 , was located mainly in nuclei of spermatogonia and in early stage primary spermatocytes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The Rb / p16 tumor suppressive pathway is abrogated frequently in human tumors , either through inactivation of the Rb or p16INK4a / CDKN2 / MTS1 tumor suppressor proteins , or through alteration or overexpression of the cyclin D 1 or cyclin dependent kinase 4 oncoproteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The mammalian cell cycle is controlled by regulators of the G 1 to S transition such as tumor suppressor proteins , p 53 and retinoblastoma ( RB ) ; cyclin D 1 and cyclin dependent kinase 4 ; and inhibitor of cyclin dependent kinase , p16INK4A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase inhibitors and dominant negative cyclin dependent kinase 4 and 6 promote survival of NGF deprived sympathetic neurons . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We therefore examined the kinetics of cyclin dependent kinase 4 ( CDK 4 ) , p16INK4A , and pRB activation during IL 6 mediated patient MM cell growth compared with growth of IL 6 unresponsive patient plasma cell leukemia ( PCL ) cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We now demonstrate that the dysplastic phenotype is associated with increased cell proliferation based on proliferating cell nuclear antigen overexpression and abnormalities in cyclin dependent kinase 4 , epidermal growth factor receptor , and p 53 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Germline mutations within the cyclin dependent kinase inhibitor 2A ( CDKN2A ) gene and one of its targets , the cyclin dependent kinase 4 ( CDK 4 ) gene , have been identified in a proportion of melanoma kindreds . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mitogenic signals are integrated through the GTPase Ras , which regulates the levels of cyclin D 1 [ 2 5 ] , a component of the cell cycle machinery that operates during G 1 phase by activating cyclin dependent kinase 4 ( Cdk 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Newly synthesized cyclin D 1 assembled with cyclin dependent kinase 4 ( CDK 4 ) to form holoenzyme complexes that phosphorylated the retinoblastoma protein inefficiently . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To elucidate the mechanisms by which endothelin ( ET ) 1 induces proliferation of mesangial cells , we investigated the involvement of the first gap phase of the cell cycle ( G 1 ) cyclin , cyclin dependent kinase 4 ( CDK 4 ) activity , and the retinoblastoma gene product ( pRb ) in ET 1 stimulated cell cycle progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
However , phosmidosine inhibited hyperphosphorylation of retinoblastoma ( RB ) protein by RB kinases such as cyclin dependent kinase 4 and cyclin dependent kinase 2 , probably as a result of the inhibition of cyclin D 1 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D type cyclins associate with a region of the DMP 1 DNA binding domain immediately adjacent to the myb repeats to form heteromeric complexes which detectably interact neither with cyclin dependent kinase 4 ( CDK 4 ) nor with DNA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The correlation coefficient ( r 2 ) between doubling time ( DT ) and cyclin D 1 in the 14 cell lines that doubled within 47 . 2 h was 0 . 4856 , while the r 2 between DT and cyclin dependent kinase 4 ( CDK 4 ) and that between DT and RB among those cell lines were 0 . 3761 and 0 . 0874 , respectively . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To understand the role of estradiol structure in diverse estrogenic responses related to cell cycle regulation , we evaluated the effects of estradiol and its analogs on cell cycle progression , and the expression of cyclin D 1 and the cyclin dependent kinase 4 ( CDK 4 ) in ER positive MCF 7 and ER transfected MCF 10AEwt5 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Several regulators of E2F transcriptional activity , including the retinoblastoma tumor suppressor ( Rb ) protein , p16Ink4a , cyclin D 1 , and cyclin dependent kinase 4 , have been shown to be targets for genetic alterations that underlie the development of human cancers . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Regulation of cyclin dependent kinase 4 during adipogenesis involves switching of cyclin D subunits and concurrent binding of p18INK4c and p27Kip1 . ^^^ We found that during terminal differentiation of mouse 3T3 L 1 preadipocytes , the level of cyclin dependent kinase 4 ( CDK 4 ) remained constant , but the subunit composition of the CDK 4 complex underwent a dynamic rearrangement . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , cyclin dependent kinase 4 , and c Myc were strongly increased in all infected livers , with even greater increases in tumors . ^^^ An increase in cyclin D1 / cyclin dependent kinase 4 complex was also demonstrated in tumors , and its functionality was confirmed by an increase in the hyperphosphorylated : hypophosphorylated retinoblastoma protein ratio . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This was shown by activation of cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 2 and by the induction of DNA synthesis . ( 2 ) PI 3 kinase activation alone was not , however , sufficient to provide for progression through the entire cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Induction of growth inhibition of 293 cells by downregulation of the cyclin E and cyclin dependent kinase 4 proteins due to overexpression of TIS 21 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The synthesis of cyclin D 1 and its assembly with cyclin dependent kinase 4 ( CDK 4 ) to form an active complex is a rate limiting step in progression through the G 1 phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Also , the level of WAF1 / Cip1 protein expression was not correlated with overexpression of cyclin D 1 , cyclin E , proliferating cell nuclear antigen , cyclin dependent kinase 4 , or p 53 in the leukemia cells . ^^^ However , the levels of cyclin D 1 , cyclin E , and cyclin dependent kinase 4 were elevated in most of the AML samples compared with that in normal marrow . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
BACKGROUND / AIMS : A checkpoint mechanism in late G 1 , whose regulation via loss of retinoblastoma protein ( pRB ) or p 16 , or overexpression of cyclin D 1 or cyclin dependent kinase 4 ( CDK 4 ) , has been proposed to constitute a common pathway to malignancy . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Calmodulin is essential for cyclin dependent kinase 4 ( Cdk 4 ) activity and nuclear accumulation of cyclin D 1 Cdk4 during G 1 . ^^^ The addition of anti calmodulin drugs to normal rat kidney cells in early G 1 inhibited cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 2 activities , as well as retinoblastoma protein phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Altered expression of cyclin D 1 and cyclin dependent kinase 4 in azoxymethane induced mouse colon tumorigenesis . ^^^ Alterations in the expression of the cell cycle regulators , cyclin D 1 and cyclin dependent kinase 4 ( Cdk 4 ) , have been implicated in malignancies of both humans and experimental animal models . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The genes investigated have been shown previously to be altered during human glial tumour progression and include the gene for the epidermal growth factor receptor ( EGFR ) , the genes for the cell cycle regulators cyclin dependent kinase 4 ( CDK 4 ) , cyclinD 1 ( cycD 1 ) , the p 16 gene ( MTS1 / INK4 ) and the retinoblastoma gene ( RB ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
There was no detectable effect of two different cAMP analogs , 8 bromo cAMP or dibutyryl cAMP on the level of the D type cyclins , cyclin E , cyclin dependent kinase 2 , cyclin dependent kinase 4 , p 53 , or the cyclin dependent kinase inhibitors p 21 or p 27 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As2O3 induced PML ( promyelocytic leukemia ) protein degradation but did not modulate expression of cell cycle related proteins , including c myc , retinoblastoma protein , cyclin dependent kinase 4 , cyclin D 1 , and p 53 , or expression of differentiation related antigens . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Comparison of deregulated expression of cyclin D 1 and cyclin E with that of cyclin dependent kinase 4 ( CDK 4 ) and CDK 2 in human oesophageal squamous cell carcinoma . ^^^ The expressions of cyclin D 1 , cyclin E , cyclin dependent kinase 4 ( CDK 4 ) , and CDK 2 were immunohistochemically examined in 90 patients with human oesophageal squamous cell carcinoma ( SCC ) to determine their relationship to the tumour behaviour and patient prognosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclins and cyclin dependent kinase 4 was evaluated by Western and Northern blotting . ^^^ The level of proteins and mRNAs for cyclins D 1 , D 2 and E started to increase 48 h after culture with a concomitant expression of platelet derived growth factor receptor beta , while the level of cyclin dependent kinase 4 and its mRNA remained unchanged . ^^^ Attenuation of the expression of cyclins D 1 , D 2 and E and platelet derived growth factor receptor beta , but not cyclin dependent kinase 4 was found in stellate cells cultured with these agents . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 overexpression in invasive breast cancers : correlation with cyclin dependent kinase 4 and oestrogen receptor overexpression , and lack of correlation with mitotic activity . ^^^ BACKGROUND : Cyclin D 1 ( CCND 1 ) and its catalytic partner cyclin dependent kinase 4 ( cdk 4 ) are known to play important roles in the G1 / S check point of the cell cycle , and CCND 1 overexpression has been reported to correlate with progression and prognosis of breast cancers . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclins D 1 and D 2 , as well as cyclin dependent kinase 4 ( cdk 4 ) , was investigated by means of immunohistochemistry in 455 gastric cancer cases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
When stimulated with serum , NRK cells rely on cyclin dependent kinase 4 ( Cdk 4 ) for their S phase entry . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Distinct role of cAMP and cGMP in the cell cycle control of vascular smooth muscle cells : cGMP delays cell cycle transition through suppression of cyclin D 1 and cyclin dependent kinase 4 activation . cAMP and cGMP are known to suppress vascular smooth muscle cell ( SMC ) proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here we show that MyoD can interact with cyclin dependent kinase 4 ( cdk 4 ) through a conserved 15 amino acid ( aa ) domain in the C terminus of MyoD . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The p 16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin dependent kinase 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of cyclin D 1 immunoprecipitates indicated complex formation with both cyclin dependent kinase 4 ( Cdk 4 ) and cyclin dependent kinase 6 ( Cdk 6 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Tumor suppressor INK 4 : quantitative structure function analyses of p18INK4C as an inhibitor of cyclin dependent kinase 4 . ^^^ The global conformations of the mutants were characterized by NMR , while the function was assayed by inhibition of cyclin dependent kinase 4 ( CDK 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Additionally , cyclin dependent kinase 4 activity was decreased in association with decreased cyclin D protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : The expressions of p 16 , cyclin dependent kinase 4 ( CDK 4 ) , proliferation cell nuclear antigen ( PCNA ) proteins in 18 cases of trophoblastic tumors , 30 cases of hydatidiform mole and 30 cases of normal villi were studied by immunohistochemical methods . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We analysed p 16 gene alteration and p 16 , cyclin dependent kinase 4 ( CDK 4 ) , CDK 6 , cyclin D 1 , cyclin D 2 , cyclin D 3 and retinoblastoma protein ( pRb ) expression in ten normal endometriums ( PE ) , 18 endometrial hyperplasias ( EH ) and 35 endometrial cancers ( EC ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The continuous high expression of cyclin D 1 , A 2 , and E , the persistent cyclin dependent kinase 4 ( CDK 4 ) and CDK 2 activities , and the presence of hyperphosphorylated forms of pRb , p 107 , and p 130 , suggest that melanoma cells acquired the capacity for autonomous growth through inactivation of all three pocket proteins and release of E2F activity , otherwise tightly regulated in normal melanocytes by external growth factors . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In familial cutaneous malignant melanoma ( CMM ) , disruption of the retinoblastoma ( pRB ) pathway frequently occurs through inactivating mutations in the p 16 ( p16INK4A / CDKN2A / MTS1 ) gene or activating mutations in the G 1 specific cyclin dependent kinase 4 gene ( CDK 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDK4 ( cyclin dependent kinase 4 ) kinase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Phosphatidylinositol 3 kinase activity regulates alpha thrombin stimulated G 1 progression by its effect on cyclin D 1 expression and cyclin dependent kinase 4 activity . ^^^ Previous results from our laboratory demonstrate that the mitogen activated protein kinase ( extracellular signal regulated kinase ( ERK ) ) pathway controls transit through G ( 1 ) phase of the cell cycle by regulating the induction of cyclin D 1 mRNA levels and cyclin dependent kinase 4 ( CDK 4 ) cyclin D 1 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Neuronal death evoked by DNA damage requires cyclin dependent kinase 4 ( Cdk 4 ) and 6 activity and is accompanied by elevation of cyclin D 1 associated kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
INK4A mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Calcineurin regulation of the mammalian G0 / G1 checkpoint element , cyclin dependent kinase 4 . ^^^ Cyclin dependent kinase 4 ( cdk 4 ) activity is controlled by the binding of regulatory subunits and inhibitory factors , as well as tyrosine and serine / threonine phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDK 4 ( the gene encoding cyclin dependent kinase 4 , an oncogene ) has exhibited germline mutations found in only three melanoma prone families to date . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These inhibitory effects were correlated with diminished cyclin dependent kinase 4 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We also observed an increase in cyclin dependent kinase 4 ( Cdk 4 ) complexes with cyclin D 1 in FB ( 1 ) treated samples ; additionally , elevated Cdk 4 activity was shown by increased phosphorylation of the retinoblastoma protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Frequent deletions or mutations of the INK 4 gene , which encodes the cyclin dependent kinase 4 inhibitor p16INK4a , have been documented in various human cancers , but little is known about the role of this tumor suppressor gene in primary breast cancer . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Inhibition of kinase activity was found to result from loss in expression of cyclins D 1 , D 3 , and E , as well as the associated cyclin dependent kinases , cyclin dependent kinase 4 and cyclin dependent kinase 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The transition from G ( 1 ) to S phase in the cell cycle requires sequential activation of cyclin dependent kinase 4 ( cdk 4 ) and cdk 2 , which phosphorylate the retinoblastoma protein , causing the release of E2F . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Inhibition of the progression through the G 1 phase of the cell cycle was further evidenced by decreased expression of cyclin D 1 and of p 34 cyclin dependent kinase 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 and its associated kinase activity CDK 4 ( cyclin dependent kinase 4 ) are major regulators of the G1 / S transition . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Semi quantitative RT PCR and Western blot analysis showed no change in the expression level of cyclin dependent kinase 4 ( CDK 4 ) , p 16 ( Ink4a ) or p 21 ( Cip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Chelators also decreased cyclins D 1 , D 2 , and D 3 , which bind with cyclin dependent kinase 4 ( cdk 4 ) to phosphorylate pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 and cyclin D 1 are required for excitotoxin induced neuronal cell death in vivo . ^^^ We investigated the relationship between the KA induced neuronal apoptosis and expression of cyclin dependent kinase 4 ( CDK 4 ) and cyclin D 1 , key regulators of cell cycle progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RESULTS : The results of these experiments confirm that the levels of wild type tumor suppressor proteins , such as p 53 , pRB , PTEN , p 14 ( ARF ) , and p 16 ( INK 4 ) , are lost or severely reduced in most gliomas , and that epidermal growth factor receptor , 2human telomerase reverse transcriptase , and cyclin dependent kinase 4 are overexpressed frequently and with a few exceptions , almost exclusively , in glioblastomas . ^^^ In particular , overexpression of epidermal growth factor receptor , human telomerase reverse transcriptase , cyclin dependent kinase 4 , and cyclin E was largely restricted to glioblastomas and was significantly associated with reduced patient survivals . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Identification of selective inhibitors of cyclin dependent kinase 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The results showed that both ephrin A 5 alpha and ephrin A 5 beta downregulated cyclin D 2 , cyclin dependent kinase 4 proteins , and their cognate receptor EphA 3 , which were associated with reduced bromodeoxyuridine incorporation in cardiomyocytes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Subcellular localization of cyclin dependent kinase 4 ( Cdk 4 ) , p27Kip1 ( p 27 ) , and phosphorylated p 27 ( pp 27 ) was determined by immunofluorescent staining followed by confocal laser microscopic analysis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
During follicular maturation , FSH induces cyclin D 2 , which promotes G 1 progression by activating cyclin dependent kinase 4 ( Cdk 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
One Rb pathway alteration seen in high grade astrocytomas is amplification of cyclin dependent kinase 4 ( CDK 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
By immunoblot analysis , we demonstrated that cyclin D 3 and cyclin dependent kinase 4 ( CDK 4 ) protein levels were inhibited by MIC treatment in the cancer cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Physical interaction of human T cell leukemia virus type 1 Tax with cyclin dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
LPTs failed to upregulate cyclin dependent kinase 4 and cyclin D 3 , but Rb phosphorylation and cyclin A and B 1 upregulation were induced by CD 2 engagement . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We report that stable overexpression of wild type PS 1 led to a decrease in cyclin dependent kinase 4 ( CDK 4 ) activity and retinoblastoma tumor suppressor protein ( pRb ) phosphorylation that correlated with decreased levels of beta catenin and cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Moreover , NGF activated TrkAS 3 receptors do not down regulate cyclin dependent kinase 4 phosphorylation of the retinoblastoma protein , essential for G ( 1 ) arrest , in comparison to NGF activated wild type TrkA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 formed complexes primarily with cyclin dependent kinase 4 ( cdk 4 ) , which were markedly activated in the regenerating liver and readily sequestered the cell cycle inhibitory proteins , p 21 and p 27 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In HepG 2 cells , this inhibition was associated with an arrest of the cell cycle in G ( 0 ) G ( 1 ) , increased cellular levels of p 21 ( CIP 1 ) , decreased levels of the hyperphosphorylated form of the retinoblastoma protein , and decreased levels of cyclin D 1 , but no significant changes were seen in the levels of the p 16 ( INK4a ) , p 27 ( KIP 1 ) , cyclin dependent kinase 4 , cyclin dependent kinase 6 , glycogen synthase kinase 3beta , or beta catenin proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Treatment with KT inhibits tumor growth through elevation of p 53 , p21 / CIP1 , and p27 / KIP1 as well as inhibition of cyclin D 3 and cyclin dependent kinase 4 protein expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the studies analyzing cell cycle regulatory molecules , corticosterone treatment of cells resulted in a strong induction ( up to approximately 10 fold over control ; P < 0 . 01 ) of KIP1 / P27 together with a decrease ( up to 98 % ; P < 0 . 01 ) in cyclin dependent kinase 4 ( CDK 4 ) and cyclin D 1 protein levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A combinatorial transduction of H RasV 12 and cyclin dependent kinase 4 ( CDK 4 ) produced human epidermal neoplasia resembling SCC . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Activation of cyclin dependent kinase 2 ( cdk 2 ) and cyclin dependent kinase 4 ( cdk 4 ) were delayed during progression to S phase , while the induction of cyclin D 1 protein , as well as the levels of cyclin E , cdk 2 , and cdk 4 were unaltered by BCL 10 ( L ) or BCL 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As in ischemic preconditioning , TNF alpha pretreatment activated NF kappaB DNA binding , STAT 3 , cyclin D 1 , cyclin dependent kinase 4 ( cdk 4 ) expression , and cell cycle entry , determined by proliferating cell nuclear antigen ( PCNA ) staining of hepatocyte nuclei . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 and its partner , cyclin dependent kinase 4 ( CDK 4 ) , are important for promoting the G 1 to S phase progression via phosphorylation of the retinoblastoma ( Rb ) protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
OBJECTIVE : To study the expression of cyclin dependent kinase 4 ( CDK 4 ) protein in oral carcinogenesis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this report , we identify the Drosophila cyclin dependent kinase 4 ( Cdk 4 ) , which exhibits embryonic mutant phenotypes identical to those in the Hopscotch / JAK kinase and stat92E / STAT mutations . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The highly expressed cyclin dependent kinase 4 ( CDK 4 ) is a cell cycle kinase that associates with cyclin D 1 for the progression through the G1 / S checkpoint , whereas overexpression of cdc 28 protein kinase 1 ( CKS 1 ) blocks the inhibition of the cyclin D1 / CDK4 complex by the CDK inhibitor p27 / Kip1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In our earlier studies , we have demonstrated that CLL cells have differential expression of genes that are associated with apoptosis and cell cycle regulation , including elevated expression of Bcl 2 , DAD 1 , Cyclin D 3 and cyclin dependent kinase 4 inhibitor . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A mutation of the p 16 ( INK4a ) binding domain of the cyclin dependent kinase 4 ( CDK 4 ) gene , R24C , has been reported in some cases of melanoma . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclin D 1 and cyclin dependent kinase 4 was also examined with double label immunohistochemistry . ^^^ Cyclin D 1 and cyclin dependent kinase 4 immunoreactivity appeared in these glial cells in parallel with the expression of PCNA . ^^^ Cyclin D 1 and cyclin dependent kinase 4 immunoreactivity appeared in these glial cells in parallel with the expression of PCNA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Direct binding of the N terminus of HTLV 1 tax oncoprotein to cyclin dependent kinase 4 is a dominant path to stimulate the kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , induction of cyclin D and cyclin dependent kinase 4 mRNA and protein was blocked upon inhibition of caspase 6 , but not caspase 3 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
On the other hand , EPA inhibited cyclin dependent kinase 4 ( CDK 4 ) activation and cyclin D 1 protein induction , a critical step for G1 / S progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cytoplasmic cyclin D 1 assembled with cyclin dependent kinase 4 ( CDK 4 ) , and the CDK inhibitors p21Cip1 and p27Kip1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The high rate of cell proliferation was accompanied by overexpression of cell cycle progression and tumorigenesis biomarkers , including proliferating cell nuclear antigen , cyclin D 1 , cyclin dependent kinase 4 , p 53 , cytokeratin 14 , epidermal growth factor receptor , and by a reduced rate of apoptosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Activating point mutations in cyclin dependent kinase 4 are not seen in sporadic pituitary adenomas , insulinomas or Leydig cell tumours . ^^^ Cyclin dependent kinase 4 ( CDK 4 ) , together with its regulatory subunit cyclin D , governs cell cycle progression through the G 1 phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These effects were associated with a decrease in cyclin D 1 expression , without a change in cyclin dependent kinase 4 or cyclin dependent kinase inhibitor , p 27 ( kip 1 ) expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Human pituitary adenomas infrequently contain inactivation of retinoblastoma 1 gene and activation of cyclin dependent kinase 4 gene . ^^^ Components of cyclinD1 / cyclin dependent kinase 4 ( CDK 4 ) / p16INK4a / pRb pathway are the frequent target of many tumor types . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Loss of p 16 contributes to p 27 sequestration by cyclin D ( 1 ) cyclin dependent kinase 4 complexes and poor prognosis in hepatocellular carcinoma . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Some key molecules involving in proliferation ( cyclin E and cyclin dependent kinase 4 ) and apoptosis ( bcl 2 and bax ) were also determined , so as to interpret the mechanisms of the alteration of tissue repairing cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Follicle stimulating hormone induced DNA synthesis in the granulosa cells of hamster preantral follicles involves activation of cyclin dependent kinase 4 rather than cyclin d 2 synthesis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Increase in cyclin D 1 levels was accompanied by a time dependent increase in cyclin D 1 dependent cyclin dependent kinase 4 ( CDK 4 ) activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , and later Cdk 2 , in association with their specific cyclin partners , regulate the G 1 to S phase cell cycle transition of mammalian cells by phosphorylation of retinoblastoma ( Rb ) family proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In co transfected Chinese hamster ovary cells , AKAP 95 strongly interacted with the three D type cyclins , but not with CDK 4 ( cyclin dependent kinase 4 ) or with p27kip1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Using a streptavidin biotin method , five cases of SDC were evaluated immunohistochemically for the presence of cyclin D 1 , CDK 4 ( cyclin dependent kinase 4 ) , p 16 ( CDK2A ) , pRb ( retinoblastoma protein ) , E2F 1 , p 53 , mdm 2 ( murine double minute 2 ) , bcl 2 , and the c erbB 2 oncoprotein to determine whether there was a correlation between the expression of these proteins and patient outcome . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cytoplasmic cyclin D 1 were complexed with cyclin dependent kinase 4 ( CDK 4 ) , and also with CDK inhibitors , p 27 ( Kip ) ( 1 ) or p 21 ( Cip ) ( 1 ) , which positively regulate assembly and nuclear accumulation of the cyclin D 1 CDK4 complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin Dependent Kinase 4 ( Cdk 4 ) is known to be an oncogene and is involved in various cancers . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Induction of beta cell proliferation and retinoblastoma protein phosphorylation in rat and human islets using adenovirus mediated transfer of cyclin dependent kinase 4 and cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Samples of NSG , pleomorphic adenoma ( PA ) , adenoid cystic carcinoma ( ACC ) , mucoepidermoid carcinoma ( MEC ) , epithelial myoepithelial carcinoma ( EMC ) , malignant myoepithelioma ( MEM ) , carcinoma ex pleomorphic adenoma ( CEPA ) , and polymorphous , low grade adenocarcinoma ( PLGA ) were examined immunohistochemically using antibodies to cyclin D 1 , cyclin dependent kinase 4 ( CDK 4 ) , retinoblastoma protein ( pRb ) , CDK inhibitor p 16 and transcription factor E2F 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have also shown that the ATRA dependent increase in p27 / kip1 protein in CAOV 3 cells leads to a decrease in the kinase activity of cyclin dependent kinase 4 ( CDK 4 ) following ATRA treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The results indicate that Smad 3 deficiency slows follicle growth , which is characterized by small follicle diameters , low levels of proliferating cell nuclear antigen , and low expression of cell cycle genes ( cyclin dependent kinase 4 and cyclin D 2 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These effects were due to nuclear factor of activated T cells c 2 ( NFATc 2 ) dependent repression of cyclin dependent kinase 4 ( CDK 4 ) expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The induced cyclin D 1 formed a complex with cyclin dependent kinase 4 ( CDK 4 ) and p 21 ( Cip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 is found to play a crucial role not only in progression through the G 1 phase as a regulatory subunit of cyclin dependent kinase 4 ( CDK 4 ) and CDK 6 , but also in many other aspects such as cell cycle , cell differentiation , transcriptional regulation and apoptosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have previously reported that the expression of nuclear localization signal tagged cyclin D 1 ( D1NLS ) and its partner cyclin dependent kinase 4 ( CDK 4 ) induces proliferation of rat neonatal cardiomyocytes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In sharp contrast , RMS in p 53 mutants display higher expression levels of cell cycle associated genes like cyclin B 1 , cyclin dependent kinase 4 and the proliferation marker Ki 67 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The three mammalian D type cyclins are thought to promote progression through the G 1 phase of the cell cycle as regulatory subunits of cyclin dependent kinase 4 and 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Restriction point transit and commitment to a new round of cell division is regulated by the activity of cyclin dependent kinase 4 and its obligate activating partners , the D type cyclins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The results of cDNA expression array revealed up regulation of cell cycle inhibitory genes such as cyclin dependent kinase 4 inhibitor , and interferon related genes such as STAT 2 and 3 , while down regulation of cyclin dependent kinase 2 and cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Most of RA induced p 27 ( Kip 1 ) was bound to cyclin D1 / cyclin dependent kinase 4 complexes , probably contributing to the decreased cyclin dependent kinase 4 kinase activity and pRb hypophosphorylation observed in RA treated cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Protein expression of cyclin D 1 and cyclin dependent kinase 4 ( Cdk 4 ) , but not p16INK4a Cdk inhibitor in the tumor was significantly reduced by vitamin K 2 or K 3 treatment , indicating that vitamins K 2 and K 3 may induce G 1 arrest of cell cycle on PLC / PRF / 5 cells in vivo . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Lack of effect of extremely low frequency electromagnetic fields on cyclin dependent kinase 4 inhibitor gene p 18 ( INK4C ) in electric energy workers . ^^^ The putative tumor suppressor gene p 18 ( INK4C ) encodes a specific inhibitor of cyclin D cyclin dependent kinase 4 inhibitor complexes having an important role in cell cyclin regulation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of HIF1alpha , cyclin D 1 , cyclin dependent kinase 4 and cyclin dependent kinase inhibitors p 16 , p 21 and p 27 was studied by immunohistochemistry . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The HTLV 1 Tax protein binding domain of cyclin dependent kinase 4 ( CDK 4 ) includes the regulatory PSTAIRE helix . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
It exhibits the transactivation activity and regulates a number of genes required for G1 / S transition , while it also binds and activates cyclin dependent kinase 4 ( CDK 4 ) independent of the inhibitory activity of p 16 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Hepatic activation of extracellular signal regulated kinase ( ERK ) 1 / 2 , p 38 kinase and expression of cyclinD 1 , cyclin dependent kinase 4 ( cdk 4 ) and proliferating cell nuclear antigen ( PCNA ) were studied . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cell cycle was analyzed by flow cytometry and protein expression , including retinoblastoma ( pRb ) , cyclin dependent kinase 4 ( CDK 4 ) and cyclin D 1 , was detected by Western blotting . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 expression is essential for neu induced breast tumorigenesis . ^^^ Although cyclin D 1 binds and activates cyclin dependent kinase 4 ( Cdk 4 ) , thereby mediating activation of a program of E2F dependent gene expression , it has been suggested that the oncogenic activities of cyclin D 1 are independent of Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Melanomas with wild type BRAF or N RAS frequently had increases in the number of copies of the genes for cyclin dependent kinase 4 ( CDK 4 ) and cyclin D 1 ( CCND 1 ) , downstream components of the RAS BRAF pathway . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have examined the role of cyclin D 1 and cyclin dependent kinase 4 ( CDK 4 ) in the cell cycle progression and proliferation of MCF 7 breast cancer cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mutually exclusive cyclin dependent kinase 4 / cyclin D 1 and cyclin dependent kinase 6 / cyclin D 2 pairing inactivates retinoblastoma protein and promotes cell cycle dysregulation in multiple myeloma . ^^^ Cyclin D 1 or D 3 expression does not vary in the clinical course , but that alone is insufficient to promote cell cycle progression unless cyclin dependent kinase 4 ( cdk 4 ) is also elevated , in the absence of cdk 6 , to phosphorylate the retinoblastoma protein ( Rb ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mutational and methylation analysis of the cyclin dependent kinase 4 inhibitor ( p16INK4A ) gene in chronic lymphocytic leukemia . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , the downstream effects of FoxO activation were found to be inhibition of cyclin dependent kinase 4 , cyclin dependent kinase 6 , and cyclin D 1 , and accumulation of p27 / Kip1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Akt induces beta cell proliferation by regulating cyclin D 1 , cyclin D 2 , and p 21 levels and cyclin dependent kinase 4 activity . ^^^ Proliferation of beta cells in caAkt ( Tg ) was associated with increased cyclin D 1 , cyclin D 2 , and p 21 levels and cyclin dependent kinase 4 ( cdk 4 ) activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 ( CDK 4 ) / cyclin D has a key role in regulating progression through late G ( 1 ) into S phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Regulated activating Thr 172 phosphorylation of cyclin dependent kinase 4 ( CDK 4 ) : its relationship with cyclins and CDK `` inhibitors ' ' . ^^^ Cyclin dependent kinase 4 ( CDK 4 ) is a master integrator of mitogenic and antimitogenic extracellular signals . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of two transcriptional corepressor proteins , SnoN and Ski , and the effect of TGFbeta 1 treatment on the expression of the SnoN protein and the cell cycle regulators p 21 , p 15 , cyclin dependent kinase 4 ( CDK 4 ) , and cyclin D 1 were also examined . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Dissecting the determinants of cyclin dependent kinase 2 and cyclin dependent kinase 4 inhibitor selectivity . ^^^ The roles of four residues of the cyclin dependent kinase active site in inhibitor selectivity were investigated by producing cyclin dependent kinase 2 mutants bearing equivalent cyclin dependent kinase 4 residues , namely F82H , L83V , H84D , and K89T . ^^^ Assay of the mutants with a cyclin dependent kinase 4 selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although histone H 1 kinase activity is not detected in cyclin D or PSK J 3 immunoprecipitates , cyclin D p34PSK J 3 complexes assembled in vitro stably bind and phosphorylate the retinoblastoma gene product ( pRb ) and an Rb like protein ( p 107 ) but do not interact with pRb mutants that are functionally inactive . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDK 6 ( PLSTIRE ) and CDK 4 ( PSK J 3 ) are a distinct subset of the cyclin dependent kinases that associate with cyclin D 1 . ^^^ Here we show that in a squamous carcinoma cell line with 11 fold amplification of the CCND 1 gene , cyclin D 1 associates specifically with p33cdk4 ( PSK J 3 ) and p38cdk6 ( PLSTIRE ) , two closely related members of the cyclin dependent kinase ( CDK ) family . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In human breast carcinoma cell line MDA 361 both cyclin D and E are overexpressed and cdk 4 and 6 are the predominate kinases which phosphorylate retinoblastoma protein and to a greater extent a novel 88 kDa protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Binding of p 15 and p 16 cell cycle regulatory proteins to the cyclin dependent protein kinase CDK 4 inhibits CDK4 / cyclin D dependent phosphorylation of retinoblastoma protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Moreover , D type cyclin dependent kinase activity specifically activates the E2F 1 promoter by relieving E2F mediated repression but is inhibited by coexpression of the cdk 4 and cdk 6 inhibitor p 16 ( CDKN 2 , MTS 1 , INK 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Suppression of cyclin D 1 but not cdk 4 or cyclin A with induction of melanoma terminal differentiation . ^^^ To identify cyclins specifically associated with control of melanoma cell proliferation , we now compared expression of cyclin A , reported to be a marker for hematological malignancies , with that of cyclin D and its cdk 4 kinase partner . ^^^ However , L tyrosine which induces melanoma terminal differentiation , selectively decreased cyclin D with no comparable effect on cdk 4 or cyclin A . ^^^ Our data suggest that cyclin D decrease with melanoma terminal differentiation could be an alternative mode of growth arrest even in cells harbouring a mutant or transcriptionally silent cdk 4 inhibitor tumor suppressor p16ink4 gene . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Growth factor induced signals govern the expression of three D type cyclins , which , in turn , function as regulatory subunits of cyclin dependent kinases ( cdks ) to control cell cycle transitions during the late G 1 interval . 32D myeloid cells , which self renew as uncommitted precursors in interleukin 3 ( IL 3 ) , express cyclins D 2 and D 3 ( but not D 1 ) in complexes with cdk 4 and cdk 2 . ^^^ Cyclin D and cdk 4 expression ceased as cells underwent growth arrest in G CSF , but cdk 2 levels were sustained . 32D cells engineered to ectopically express D type cyclins exhibited contracted G 1 intervals with a compensatory lengthening of S phase but remained IL 3 dependent for cell growth ; those overexpressing cyclins D 2 and D 3 ( but not D 1 ) were unable to differentiate and died in G CSF . ^^^ Conversely , the introduction of a catalytically inactive cdk 4 mutant into cells overexpressing cyclin D 2 restored their G CSF response . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Amount of cyclin D 3 and cdk 4 mRNA increased in the c fos B cells at 6 h earlier than that in the control B cells , indicating that the kinetics of these mRNA expressions correlate with the acceleration of cell cycle progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
However , in these same cells the association of cdk 4 with cyclin D 1 , PCNA , and Waf 1 is disrupted . ^^^ These results show that large T antigen expression in human fibroblasts selectively uncouples cyclin D 1 from cdk 4 , and subsequent immortalization of these cells results in additional changes to the cyclin D 1 dependent cell cycle regulatory pathways . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated mouse skin tumors . p16INK4a and p15INK4b are cell cycle regulators that specifically bind to and inhibit the cyclin D dependent kinases , cdk 4 and cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
One probable pathway for this growth inhibition is through the TGF beta mediated up regulation of the cyclin dependent kinase ( CDK ) inhibitor p15INK4B , which specifically inhibits the enzymatic activities of CDK 4 and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have explored the interaction of p 21 with the currently known Cdks . p 21 effectively inhibits Cdk 2 , Cdk 3 , Cdk 4 , and Cdk 6 kinases ( Ki 0 . 5 15 nM ) but is much less effective toward Cdc2 / cyclin B ( Ki approximately 400 nM ) and Cdk5 / p35 ( Ki > 2 microM ) , and does not associate with Cdk7 / cyclin H . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TNF alpha did not affect complexes between cyclin D and Cdk 2 , Cdk 4 , and Rb proteins in MCF 7 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although the residual cyclin D 3 protein forms a complex with cdk 4 protein , cyclin D 3 dependent kinase activity is severely impaired . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The delayed G 0 > S progression in fos expressing cells was accompanied by the inappropriate levels or kinetics of expression of several cell cycle regulated genes ( cyclin D 1 , cdc 2 , cdk 2 , cdk 4 and rb ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Amplifications of CDK 4 and CCND 1 ( cyclin D 1 ) were observed in 11 % and 4 % of the sarcomas respectively , but never in tumours with CDKN 2 deletions . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of certain cell cycle regulatory proteins : cdk 1 , cdk 2 , cdk 4 , cyclin A , cyclin B , cyclin E , Bcl 2 and PCNA was examined in peripheral blood lymphocytes ( PBL ) from 25 cases of chronic lymphocytic leukemias ( CLL ) in order to analyze a possible cell cycle involvement of CLL lymphocytes . ^^^ The expression of cdk 4 and cyclin E , both known to act in early cell cycle stage , was approximately on the same level in all groups of lymphoid pathology examined . ^^^ In particular , we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk 4 positive , ie they expressed these markers over twice the level of non stimulated healthy PBL . ^^^ The presence of cdk 4 and cyclin E in the blood cells of the majority of CLL cases studied , as well as cdk 1 and cdk 2 in some cases , indicate that the CLL cells are not quiescent , but are blocked in an early stage of the G 1 cell cycle phase , and / or that the expression of these proteins is pathologically deregulated . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The point in G 1 at which cells irrevocably commit to DNA synthesis is controlled by protein complexes consisting of cyclin dependent kinases ( CDK 4 or CDK 6 ) and cyclins ( D 1 , D 2 or D 3 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
G 1 progression in mammalian cells requires the activity of the cyclin D dependent kinases Cdk 4 and / or Cdk 6 and the cyclin E dependent kinase Cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Progression through the G 1 phase of the cell cycle is regulated in part by the D type cyclin dependent kinases , cdk 4 and cdk 6 . ^^^ Like human p16INK4a , mouse p16INK4a binds specifically to cdk 4 and cdk 6 in vitro and inhibits the phosphorylation of the retinoblastoma protein , pRb , by each of these cyclin D dependent kinases . ^^^ Expression vectors encoding human or mouse p16INK4a caused G 1 phase arrest in NIH3T3 fibroblasts , and cyclin D 1 and cdk 4 dependent pRb kinase activities were inhibited in the p16INK4a arrested cells . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D type cyclins and cyclin dependent kinase ( cdk 4 ) are likely involved in regulating passage of cells through the G 1 phase of the cell cycle . ^^^ Radiation survival curves were obtained at a dose rate of either 8 cGy / min or 1 Gy / min for subclones of the IL 3 dependent hematopoietic progenitor cell line 32D cl 3 expressing transgenes for either cyclin D 1 , D 2 or D 3 or cdk 4 . ^^^ Cells overexpressing transgenes for each D type cyclin or Bcl 2 had an increased number of cells in S phase compared to parent line 32D cl 3 ; however , overexpression of cdk 4 had no effect on cell cycle distribution . ^^^ Western analysis revealed induction of cyclin D protein levels by irradiation , but no change in the levels of cdk 4 , p 53 or p 21 . ^^^ There was no significant change in the D 0 , but a significant increase in the n for cyclin D or cdk 4 transgene overexpressing clones at 1 Gy / min ( P < 0 . 017 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Glucocorticoids also inhibit expression of the catalytic partner of cyclin D 3 , Cdk 4 . ^^^ Cells transformed with Cdk 4 expression vectors , with or without cyclin D 3 expression vectors , also undergo G 0 arrest in the presence of dexamethasone . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The protein levels of cyclin E , CDK 2 , and CDK 4 were not affected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mutations and overexpression of cyclins and cyclin dependent kinases , mainly cyclin D 1 and Cdk 4 , have been reported and proposed to be oncogenic events . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The tandemly linked p16INK4aMTS1 and p15INK4b / MTS2 genes on chromosome 9 , band p 21 encode proteins that function as specific inhibitors of the cyclin D dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In both sensitive and resistant cell lines , TGF beta 1 treatment did not affect cdk 2 , cdk 4 , cyclin E and cyclin D 1 mRNA and protein levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunoprecipitation of cyclin D 1 demonstrated its association with cdk 4 but not cdk 5 in regenerating liver . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 is dispensable for G 1 control in retinoblastoma gene deficient cells independently of cdk 4 activity . ^^^ Consistent with a potential role of cyclin D / cdk4 in phosphorylation of pRB , monoclonal anti cyclin D 1 antibodies supporting the associated kinase activity failed to significantly affect proliferation of RB positive cells , whereas the antibody DCS 6 , unable to coprecipitate cdk 4 , efficiently inhibited G 1 progression and prevented pRB phosphorylation in vivo . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Novel INK 4 proteins , p 19 and p 18 , are specific inhibitors of the cyclin D dependent kinases CDK 4 and CDK 6 . ^^^ Two novel members of the mouse INK 4 gene family , p 19 and p 18 , that specifically inhibit the kinase activities of CDK 4 and CDK 6 , but do not affect those of cyclin E CDK 2 , cyclin A CDK 2 , or cyclin B CDC 2 , were isolated . ^^^ Like the previously described human INK 4 polypeptides , p16INK4a / MTS1 and p15INK4b / MTS2 , mouse p 19 and p 18 are primarily composed of tandemly repeated ankyrin motifs , each ca . 32 amino acids in length , p 19 and p 18 bind directly to CDK 4 and CDK 6 , whether untethered or in complexes with D cyclins , and can inhibit the activity of cyclin D bound cyclin dependent kinases ( CDKs ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The G1 / S checkpoint is mainly dictated by the kinase activities of the cyclin D CDK 4 and / or cyclin D CDK 6 complex and the cyclin E CDK 2 complex . ^^^ The p 19 fusion protein can associate in vitro with CDK 4 but not with CDK 2 , CDC 2 , or cyclin A , B , E , or D 1 to D 3 . ^^^ Addition of p 19 protein can lead to inhibition of the in vitro kinase activity of cyclin D CDK 4 but not that of cyclin E CDK 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
While transfer to low serum induced the retinoblastoma protein to enter its dephosphorylated state , and cyclin A , cyclin B and cdc 2 levels to decrease , all as normal , cyclin E , cdk 4 , cdk 2 and the exogenous cyclin D 2 persisted at high levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D type cyclins form active complexes with Cdk 4 or Cdk 6 earlier than E type cyclin does with Cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , both CDK 4 and CDK 2 associated kinase activities were downregulated in cells overexpressing WT 1 , whereas the levels of CDK 4 , CDK 2 , and cyclin D 1 expression were unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Regulation of synthesis and activity of the PLSTIRE protein ( cyclin dependent kinase 6 ( cdk 6 ) ) , a major cyclin D associated cdk 4 homologue in normal human T lymphocytes . ^^^ The PLSTIRE protein ( cyclin dependent kinase 6 ( cdk 6 ) ) , which shares extensive sequence homology ( approximately 70 % ) with cdk 4 , was identified as the earliest inducible member of the cdk family of proteins in human T lymphocytes induced to proliferate in vitro by stimulation either with phorbol 12 , 13 dibutyrate and ionomycin ( PDB / I ) or PHA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
During the G 1 phase , cyclin D 1 is induced by M CSF / CSF 1 stimulation and forms enzymatically active complex with cdk 4 . ^^^ The enzymatic activity of the cyclin D 1 and cdk 4 complex could be negatively regulated by recently reported inhibitory proteins to determine the timing for entry into S phase in macrophages . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Differential requirements for interleukin 2 distinguish the expression and activity of the cyclin dependent kinases Cdk 4 and Cdk 2 in human T cells . ^^^ Cyclin D 2 , a Cdk 4 partner , showed similar patterns of regulation as Cdk 4 . ^^^ The increases in Cdk 4 and cyclin D 2 expression seen in competent T cells were functionally significant since Cdk 4 immunoprecipitates from these cells phosphorylated recombinant RB protein in vitro . ^^^ These data demonstrate that 1 ) the signals that lead to induction of competence in T cells stimulate an IL 2 independent and CsA resistant phase of Cdk 4 and cyclin D 2 expression , Cdk 4 kinase activity , and Cdk 2 kinase activity , and 2 ) IL 2 stimulates a second phase of Cdk 4 and cyclin D 2 expression and de novo expression of Cdk 2 in these cells . ^^^ The data show that the expression and activity of these major cell cycle regulatory proteins are controlled differentially by growth factors and indicate a role for Cdk 4 and cyclin D 2 in T cell cycle entry and / or early G 1 progression and for Cdk 2 in later G 1 progression and G1 / S transition . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western assays demonstrated , further , that cyclin D 3 was complexed with the cyclin dependent kinases , cdk 2 and cdk 4 , in differentiated L 6 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
One of the crucial functions of D cyclins is their ability to bind to a cyclin dependent kinase ( Cdk 4 ) . ^^^ In exponentially growing cultures , TGF beta 1 blocked DNA synthesis and suppressed cyclin D 1 mRNA and protein expression , whereas the levels of cyclins D 2 , D 3 and Cdk 4 remained relatively unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D type cyclins , in association with the cyclin dependent kinases Cdk 4 or Cdk 6 , regulate events in the G 1 phase of the cell cycle and may contribute to the phosphorylation of the retinoblastoma gene product ( Rb ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In a myeloid cell line dependent on interleukin 3 ( IL 3 ) for proliferation , expression of the cyclin dependent kinase Cdk 4 and D type cyclin partners , D 2 and D 3 , in mid G 1 was found to be directly related to the concentration of IL 3 . ^^^ Constitutive expression of Cdk 4 , but not cyclin D 2 or D 3 , increased cyclin D 2 associated Rb kinase activity and this activity could no longer be inhibited by TGF beta 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TGF beta has no effect on the steady state level of cdk 4 , while having only a modest inductive effect on cyclin D 1 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclins D 1 , D 2 and D 3 preferentially associate with two closely related members of the cyclin dependent kinase family , Cdk 4 and Cdk 6 and the various complexes are each capable of phosphorylating the retinoblastoma gene product ( pRb ) , at least in vitro . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These include kinase complexes containing cyclin A , cyclin B , and cyclin D , associated either with CDC 2 , CDK 2 , CDK 4 , or CDK 5 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Likewise , the expression of cdk 4 , cyclin A and DNA polymerase alpha is dependent of the synergistic effect of both the Ca2+ / calmodulin and the protein kinase C pathways . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
It was initially observed in complexes containing CDK 4 , cyclin D , and proliferating cell nuclear antigen ( PCNA ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cell cycle dependent phosphorylation of the RB tumor suppressor protein is mediated by a family of G 1 cyclin dependent kinases ( cdks ) and cyclins including the activated cdk 4 : cyclin D complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Both normal and transformed T cells contained PCNA in association with cdk 2 , cdk 4 , cdk 5 , and cdk 6 , with the amount of PCNA associated with these molecules increasing in the order listed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Coexpression of cyclin D 1 with its primary catalytic subunit , Cdk 4 , or with Cdk 2 , also prevented repair . ^^^ Again , these effects were abolished by coexpression of cyclin D 1 together with PCNA , but not with Cdk 4 or Cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A clear cell cycle dependent expression was found with cyclins A ( S+G2 ) , B ( G 2 ) and E ( late G 1 and S ) , while other cell cycle genes showed only very weak ( cdk 2 ) or no periodic expression ( cyclin D 1 , cyclin D 2 and cdk 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The D type cyclin dependent kinases CDK 4 and CDK 6 are complexed with many small cellular proteins ( p 14 , p 15 , p 16 , p 18 , and p 20 ) . ^^^ By use of a yeast interaction screen to search for CDK 6 interacting proteins , we have also identified an 18 kD human protein , p 18 , that is a homolog of the cyclin D CDK 4 inhibitors p 16 ( INK4A / MTS1 ) and p 14 ( MTS2 / INK4B ) . ^^^ Distinct from the p21 / p27 family of CDK inhibitors that form ternary complexes with cyclin CDKs , only binary complexes of p 14 , p 16 , and p 18 were found in association with CDK 4 and / or CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
AGM 1470 completely abolishes the growth factor induced mRNA expression of cdc 2 and cyclin A and partially inhibits that of cyclin E but has little effect on the mRNA level of cdk 2 , cdk 4 , or cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Using a yeast interaction screen to search for proteins that interact with cyclin D 1 Cdk4 , we identified a 27 kDa mouse protein related to the p 21 cyclin Cdk inhibitor . p 27 interacts strongly with D type cyclins and Cdk 4 in vitro and more weakly with cyclin E and Cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Differential expression and regulation of Cyclin D 1 protein in normal and tumor human cells : association with Cdk 4 is required for Cyclin D 1 function in G 1 progression . ^^^ In this study we have surveyed by immunoblotting the protein levels of Cyclin D 1 , D 2 , D 3 and their catalytic partners , Cdk 4 and Cdk 6 in normal and transformed human cells . ^^^ In cells displaying active pRb , Cyclin D 1 was found associated with Cdk 4 regardless of whether the p 53 gene was wild type or mutant . ^^^ In cells lacking pRb function , Cyclin D 1 was dissociated from Cdk 4 . ^^^ These results show that ( 1 ) in the absence of pRb , Cyclin D 1 is expressed at low levels , is dissociated from Cdk 4 and becomes dispensable in G 1 ; ( 2 ) Cyclin D 1 needs to be associated with its catalytic subunit , Cdk 4 , to function as a positive regulator of G 1 progression . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In transformed cells , CDK 4 totally dissociates from cyclin D , PCNA , and p 21 and , instead , associates exclusively with a polypeptide of 16 kD ( p 16 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In human umbilical vein endothelial cells , the protein kinase C ( PKC ) stimulation during the early G 1 phase leads to potentiations in growth factor stimulated DNA synthesis , the activation of cdc 2 and cdk 2 cyclin dependent kinases , and the mRNA expression of cdc 2 , cyclins A , D 1 and E , but not cdk 2 or cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ectopic expression of cyclin D 2 in rodent fibroblasts , either alone or together with exogenous cdk 4 , shortened their G 0 to S phase interval and reduced their serum dependency , but cyclin D 2 alone did not alter cell size significantly . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Coexpression of the three D type cyclins with the cyclin dependent kinase ( cdk 4 ) in insect cells generated Rb kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cdk 4 ( cyclin dependent kinase ) , a major catalytic subunit of the mammalian D type G 1 cyclins , can phosphorylate Rb in vitro , and at least one D type cyclin , D 2 , directs the phosphorylation of Rb in vivo . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Direct binding of cyclin D to the retinoblastoma gene product ( pRb ) and pRb phosphorylation by the cyclin D dependent kinase CDK 4 . ^^^ Complexes of the cyclin dependent kinase , cdk 4 , and each of three different D type cyclins , assembled in insect Sf 9 cells , phosphorylated a pRb fusion protein in vitro at sites identical to those phosphorylated in human T cells . ^^^ The transcription factor E2F 1 also bound to pRb in insect cells , and coexpression of cyclin D cdk 4 complexes , but neither subunit alone , triggered pRb phosphorylation and prevented its interaction with E2F 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The INK4a ( MTS 1 , CDKN 2 ) gene encodes an inhibitor ( p16INK4a ) of the cyclin D dependent kinases CDK 4 and CDK 6 that blocks them from phosphorylating the retinoblastoma protein ( pRB ) and prevents exit from the G 1 phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
NGF treatment of cells completely inhibited the activity of the cyclin dependent protein kinases CDK 2 and CDK 4 . ^^^ Levels of CDK 2 and CDK 4 were decreased following NGF treatment of cells ; however , levels of cyclin E and cyclin D were increased . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Extracts prepared from quiescent mouse mammary epithelial cells are shown to act in a dominant manner to specifically inhibit the histone H 1 kinase activity of preformed / active cdk 2 , cdk 4 , cyclin A , or cyclin E complexes from G 1 S cell extracts . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunoaffinity purified Cak 1 phosphorylated monomeric Cdc 2 and Cdk 2 , but not Cdk 4 ; the phosphorylation of both Cdc 2 and Cdk 2 were increased in the presence of recombinant cyclin A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Interestingly , the shortening of G 1 was accompanied by a rapid down regulation of D type cyclins and their partner , cyclin dependent kinase type 4 ( cdk 4 ) , while expression of S and G 2 M associated cell cycle regulators ( cyclin A and cdk1 / cdc2 ) remained high until the cells arrested in G 1 72 96 h after differentiation induction . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Progression through the G 1 phase of the cell cycle is dependent on the activity of holoenzymes formed between D type cyclins and their catalytic partners , the cyclin dependent kinases cdk 4 and cdk 6 . p16INK4a , p15INK4b , and p18INK4c , a group of structurally related proteins , function as specific inhibitors of the cyclin D dependent kinases and are likely to play physiologic roles as specific regulators of these kinases in vivo . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The roles of the cyclin dependent kinase ( Cdk ) family in murine germ cell development have been examined by studying the expression of five Cdk family genes ( Cdc 2 , Cdk 2 , Cdk 4 , Pctaire 1 , and Pctaire 3 ) in mouse reproductive organs . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Biochemical studies suggest that p16INK4 mediates its effects by specifically inhibiting the G 1 cyclin dependent kinases CDK 4 and CDK 6 , thereby regulating the progression through G 1 into S phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As the p 16 protein is involved in a cell cycle regulatory pathway consisting of at least pRb , cdk 4 and cyclin D 1 , the tumours were also screened for amplifications of the last two genes . ^^^ However , highly elevated CDK 4 mRNA levels , compared with that seen in a panel of normal tissues , were observed in 76 % of the tumours , accompanied in 71 % of the cases by high expression of the CCND 1 cyclin activator . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Infrequent alterations of the p 15 , p 16 , CDK 4 and cyclin D 1 genes in non astrocytic human brain tumors . ^^^ In this study , p 15 , p 16 , CDK 4 and cyclin D 1 genes were analyzed in 69 nonastrocytic human brain tumors , including 17 oligodendrogliomas , 16 medulloblastomas / primitive neuroectodermal tumors ( PNETs ) , 14 ependymomas and 22 meningiomas . ^^^ Southern blot analyses revealed no amplification of CDK 4 and cyclin D 1 genes in any of the neoplasms analyzed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
An incremental binding of p 21 with Cdk 4 paralleled the inhibition of cyclin D1 / Cdk4 kinase and a similar rise in Cdk 2 binding to p 21 was associated with inhibition of cyclin E and cyclin A dependent kinases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cyclin D 1 protein was able to associate with the cell cycle dependent kinases , cdk 4 and cdk 6 , but not always with proliferating cell nuclear antigen in selected cell lines tested , representing a novel finding . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
PMA inhibited the histone H 1 kinase activity of Cdk 2 , which increased from about 9 h , whereas PMA did not inhibit the pRb kinase activities of cyclin D associated kinase ( s ) and Cdk 4 , detectable from 0 3 h . ^^^ These results suggested that the PMA induced inhibition of pRb phosphorylation is not mediated by suppressing cyclin D associated kinase ( s ) including Cdk 4 , but involves the suppression of Cdk 2 activity that results from the reduced expression of cyclins E and A . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Moreover , the Cdk 2 cyclin D 1 complex was not activated by incubation with Cdk 4 or cyclin E . ^^^ In human WI 38 cells , cyclin D 1 began to form a complex with Cdk 2 as well as with Cdk 4 from the mid G 1 phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Studies on cyclin dependent kinase ( cdk ) activation revealed that complement increased cyclin dependent cell cycle associated kinase 2 activity in G 1 , while cdk 2 and cdk 4 showed low activity during G 1 progression . ^^^ However , the activity of cdk 4 complexed with cyclin D 2 showed a marked increase in G1 / S transition . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 binds to Cdk 4 and forms a complex , then binds to and phosphorylates Rb protein thus triggering cells to progress from G0 / G1 to S and thus drives cellular proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Staurosporine treatment did not cause reductions in the protein levels of CDK 4 , cyclin D 1 , CDK 2 , or cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Interactions of cyclin D 1 , Cdk 4 , and p21Cip1 . ^^^ Cyclin D 1 , Cdk 4 , and p 21 mRNA and protein levels were determined by standard Northern and Western blot analyses , respectively . ^^^ Cyclin D 1 , Cdk 4 , and p 21 protein complex formation was analyzed by immunoprecipitating the complexes from cell lysates with an antibody to one of the constituents , followed by SDS polyacrylamide gel electrophoresis ( SDS PAGE ) and Western blot analysis of the precipitated complexes using antibodies to the other proteins . ^^^ Cyclin D 1 and Cdk 4 mRNA levels remained relatively constant during contact inhibition , whereas immunoblotting showed that the levels of cyclin D 1 and Cdk 4 proteins decreased by 70 . 9 % and 68 . 7 % , respectively , comparing day 3 with day 9 during density arrest . ^^^ The levels of cyclin D 1 increased 5 . 8 fold and Cdk 4 increased by 4 . 4 fold by 24 hours after reseeding the day 9 density arrested cultures , coincident with the increase in DNA synthesis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The regulation of the D type cyclin dependent kinase ( CDK 4 and CDK 6 ) activity appears to be the key step in the progression of eukaryotic cells through the G 1 cell cycle phase . ^^^ Moreover , employing the human native partially purified p 16 ( INK 4 ) or the pure recombinant protein , we have been able to demonstrate in vitro the dissociation of CDK 4 cyclin D 1 complex and the formation of CDK 4 p16 ( INK 4 ) bimolecular complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The remaining two mutations , a G to W mutation at position 101 ( Gl01W ) and V126D , both of which are associated with familial melanoma , were found to be temperature sensitive for binding to Cdk 4 and Cdk 6 in vitro , for inhibiting cyclin D 1 Cdk4 in a reconstituted pRb kinase assay , and for increasing the proportion of G 1 phase cells following transfection . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Our results showed that ( 1 ) CDK 4 and cyclin D 3 are the G1 / S regulators in B precursor cells ; ( 2 ) their expression levels are unchanged between the cells in G 1 arrest and cycling cells ; and ( 3 ) they are present in an associated form even when the cell cycle stage is arrested at G 1 . ^^^ Thus , the regulation of the expression of CDK 4 and cyclin D 3 or regulation of their assembly are not the mechanisms for activating CDK 4 in the B precursor cells . ^^^ Thus , we present a possibility that CDK 4 activation might be regulated by molecules associated with the CDK 4 cyclin D 3 complex in IL 7 dependent manner . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Flavopiridol induces G 1 arrest with inhibition of cyclin dependent kinase ( CDK ) 2 and CDK 4 in human breast carcinoma cells . ^^^ In this study , we used MCF 7 breast carcinoma cells that are wild type for p 53 and pRb positive and contain CDK 4 cyclin D 1 and MDA MB 468 breast carcinoma cells that are mutant p 53 , pRb negative , and lack CDK 4 cyclin D 1 to investigate the G 1 arrest produced by Flavopiridol . ^^^ Recombinant CDK 4 cyclin D 1 was inhibited potently by Flavopiridol ( Kiapp , 65 nM ) , competitive with respect to ATP . ^^^ Cyclin D and CDK 4 levels were not different at 3 hr , but cyclin D levels and CDK 4 kinase activity decreased thereafter . ^^^ Cyclin E and A levels were not altered to the same extent as cyclin D , and neither CDK 4 nor CDK 2 levels were changed in response to Flavopiridol . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDK 4 is a cyclin D dependent kinase that controls progression through G 1 of the mammalian cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 and its associated kinase ( CDK 4 / 6 ) phosphorylate pRB in vitro , and therefore are thought to contribute to the regulation of pRB function . ^^^ Conversely , of the 4 pRB ( + ) HCLs and 3 pRB ( + ) plasmacytomas , only 1 of each was cyclin D 1 ( + ) . pRB appeared to exist primarily in the underphosphorylated ( fastest migrating ) form on Western blot , despite the fact that cyclin D 1 was complexed to CDK 4 , a form in which it normally phosphorylates pRB . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Relative mRNA expression levels were assessed using a rapid and sensitive Reverse Transcriptase Polymerase Chain Reaction ( RT PCR ) assay called the `` Primer dropping ' ' method . p16INK4 , a specific inhibitor of the cyclin D associated kinases CDK 4 and CDK 6 , was , in addition to p 21 and cyclin D 1 , overexpressed in higher passage cells , while the abundance of the D type kinase mRNAs remained relatively constant . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This decrease is fairly specific , because the level of other Cdks such as Cdk 2 and Cdk 4 and cyclins such as cyclin D 2 , cyclin E and cyclin A , did not change significantly even after 24 h treatment with herbimycin A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of metabolically labelled cells revealed that cyclin D 2 , cyclin D 3 , and cdk 4 were also partnered with p27kip1 in quiescent BALB / c 3T3 cells and that this association decreased after platelet derived growth factor ( PDGF ) treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The G 1 associated cyclin D 1 was not expressed at any stage of the anti Ig + IL 4 induced B cell cycle . cdk 2 , cdk 4 , and cdk 6 were induced during G 1 , whereas cell division cycle 2 ( cdc 2 ) was induced concomitantly with S phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D and CDK 4 , however , were not induced . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RA , however , did not affect c myc or cyclin D 1 gene expression , nor did it significantly change the mRNA or protein levels of cyclins D 3 or E or cyclin dependent kinases ( CDK ) Cdk 2 or Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
One of these genes , cyclin D 1 , is expressed in early G 1 phase , and its protein product , together with the cyclin dependent kinases CDK 4 and CDK 6 , mediates the phosphorylation and functional inactivation of the retinoblastoma protein ( pRb ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression of its product , p 16 , has been shown to block the transition through the G1 / S phase of the cell cycle in a pRb dependent fashion by inhibiting the cyclin D dependent kinases cdk 4 and cdk 6 . ^^^ RESULTS : We have identified a 20 residue synthetic peptide corresponding to amino acids 84 103 of p 16 that interacts with cdk 4 and cdk 6 , and inhibits the in vitro phosphorylation of pRb mediated by cdk 4 cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Also in contrast with TGF beta , EGF causes a strong upregulation of cyclin D 1 , while neither growth factor affects cdk 4 protein levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In vitro and in nonproliferating cells , p 27 associates with and inhibits cyclin / cycin dependent kinase ( CDK ) holoenzymes containing either CDK 4 , CDK 6 , or CDK 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , TNP 470 had no or less marked effect on cyclin D 1 and cdk 4 mRNA levels induced by PDGF BB . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Staurosporine resistance accompanies DNA tumor virus induced immortalization and is independent of the expression and activities of ERK 1 , ERK 2 , cyclin A , cyclin dependent kinase ( cdk ) 2 , and cdk 4 . ^^^ Staurosporine resistance was not the result of increased activities and / or expression of cyclin A , cyclin dependent kinase ( cdk ) 2 , cdk 4 , or the mitogen activated kinases ERK 1 and ERK 2 . ^^^ Although increased activities and / or expression of cyclin A and cdk 2 and cdk 4 proteins , but not ERK 1 or ERK 2 , were associated with immortalization , similar increases were found in staurosporine sensitive precrisis cells expressing SV 40 tumor antigens . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In myotubes , p 130 also forms complexes with cyclin D 3 as well as cyclin E , cdk 2 , and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A number of proteins that are known to be involved in the regulation of the cell cycle , such as cyclin dependent kinase ( CDK ) 2 and CDK 4 , proliferating cell nuclear antigen ( PCNA ) , p 53 , c fos , and the CDK inhibitor p 16 and p 27 were investigated by Western analysis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Recently , two cell cycle regulators that inhibit the cyclin D 1 associated kinases cdk 4 and cdk 6 have been identified : p 16 and p 15 , the products of the INK4A ( also known as CDKN 2 , MTS 1 ) and INK4B ( also known as MTS 2 ) putative tumor suppressor genes located on 9p21 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 immunoprecipitates contained Cdk 4 but no detectable Cdk 2 and displayed pRb but not histone H 1 kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cyclin D dependent kinases CDK 4 and CDK 6 trigger phosphorylation of the retinoblastoma protein ( RB ) late in G 1 phase , helping to cancel its growth suppressive function and thereby facilitating S phase entry . ^^^ Although specific inhibition of cyclin D dependent kinase activity in vivo can prevent cells from entering S phase , it does not affect S phase entry in cells lacking functional RB , implying that RB may be the only substrate of CDK 4 and CDK 6 whose phosphorylation is necessary for G 1 exit . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The first group , including p16Ink4a , p15Ink4b , p18Ink4c and p19Ink4d , is specific for the G 1 CDKs , CDK 4 and CDK 6 , inhibiting the kinase activity of cyclin D / CDK4 CDK 6 complexes on pRb . p16Ink4a , down regulated by pRb , inhibits G 1 CDKs by competition with cyclin D ; p15Ink4b , the synthesis of which is induced by TGF beta , seems to be a mediator of TGF beta mediated cell cycle arrest . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , we show that the growth suppressive effect of cyclin D 1 correlates with cyclin D 1 binding to cdk 4 rather than to proliferating cell nuclear antigen PCNA . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
An obvious focus is the so called restriction point in late G 1 , and current evidence suggests that this is in part determined by the phosphorylation of the retinoblastoma protein ( Rb ) by the cyclin D dependent kinases , CDK 4 and CDK 6 . ^^^ Many human tumours have been shown to have chromosomal abnormalities that directly affect components of this pathway , resulting in either the functional inactivation of p 16 or Rb or the excessive activity of cyclin D 1 or CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
However , cellular levels of their partners , cdk 4 and cyclin E , remain unchanged as does the level of pRB . ^^^ Re entry is accompanied by a reduction in un / hypophosphorylated pRB , an induction of cyclin D 1 and cdk 2 , but no change in cdk 4 , cyclin E , or E2F 1 . ^^^ The presence of cyclin E and cdk 4 in differentiating villus enterocytes emphasizes that these cells retain part of their proliferative heritage expressed 24 72 h earlier in the crypt . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D , CDK 4 and p 16 expression in colorectal cancer ] . ^^^ Cyclin D / CDK4 complex phosphorylates retinoblastoma gene product and p 16 inhibits CDK 4 in competition with cyclin D . ^^^ In this study we examined the expression of cyclin D , CDK 4 and p 16 in adenoma carcinoma sequence of colorectum . ^^^ Western blot analysis also revealed that primary regions of advanced colorectal cancer tissues showed 4 . 61 , 3 . 30 , 1 . 65 and 8 . 03 fold overexpression on the average in cyclin D 1 , cyclin D 2 , CDK 4 and p 16 respectively . ^^^ These results indicate that both cyclin D and CDK 4 may contribute to phosphorylation of pRB . p 16 overexpression would be induced as a brake at G1 / S transition through pRB phosphorylation by CDK 4 overexpression in advanced colorectal carcinomas . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
However , like vertebrate cdk 4 and cdk 6 , Drosophila cdk4 / 6 binds also to a D type cyclin according to the results of two hybrid experiments in yeast . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Interestingly , Western blot analysis also demonstrated that iron chelation decreased the protein levels of the cyclin D and cdk 4 subunits as compared to control and produced a change in retinoblastoma protein phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The transition from G 1 to S phase is dependent on D cyclins in complex with cdk 4 or cdk 6 and cyclin E complexed with cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunoprecipitation experiments revealed that p27Kip1 preferentially associated with CdK 4 in Ang 2 treated LLC PK 1 cells and that the activity of this kinase was inhibited after Ang 2 treatment , an effect that may be generated by increased p27Kip1 binding to cyclin D 1 CdK4 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We studied several cyclin dependent kinases ( cdk 1 , cdk 2 , cdk 4 , cdk 6 ) and cyclins ( cyclin A , cyclin B 1 , cyclin D 3 and cyclin E ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In asynchronously growing WM 35 , TGF beta caused reductions in cyclin D 1 , cyclin A and cdk 4 proteins and their associated kinase activities and an increase in both p21Cip1 / WAF1 and p27Kip1 . ^^^ It has been proposed that in TGF beta arrested epithelial cells , up regulation of p15INK4B and of p15INK4B binding to cdk 4 serves to destabilize the association of p27Kip1 with cyclin D1 / cdk4 , promoting p27Kip1 binding and inhibition of cyclin E / cdk2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Thus suppression of p 45 , cyclin D2 / Cdk 4 , and cyclin B1 / Cdc 2 expression and / or activities is targeted both by contact inhibition and by TGF beta 1 and may define common mechanisms through which these negative growth signals are integrated . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The SK 29 MEL 1 cell line harboring an R24C mutation in Cdk 4 expressed wild type pRb and overabundant p 16 , the latter preventing endogenous Cdk 6 but not Cdk 4 from associating with cyclin D 1 . ^^^ These data strongly support the candidacy of Cdk 4 as a novel proto oncogene , provide further evidence for the p 16 cyclin D / Cdk pRb pathway as a functional unit , and suggest that deregulation of this checkpoint may represent a common step in the multistep progression of sporadic malignant melanomas . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These proteins bind to , and regulate cyclin dependent kinase ( CDK ) , such as CDK 4 , responsible for phosphorylation of retinoblastoma ( RB ) and dissociation of RB E2F1 inhibitory complexes , thereby allowing progression through the cell cycle . ^^^ Constitutive CDK 4 activity in melanomas may be the results of inactivation of the negative regulators known as CDK inhibitor p16INK4 , and / or p 21 ; and / or overexpression of cyclin D , the positive CDK 4 regulator . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The down modulating effects of the inhibitors on the expression of the following cell cycle regulators have been examined : c myc , cyclin D 1 and D 2 , cdk 4 , Rb phosphorylation , E2F binding activity , ribonucleotide reductase subunits , and PCNA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
On the other hand , there was no significant difference in expression of proteins such as Rb , p 16 , cdk 4 , cdk 6 , cyclin A and cyclin D 1 between the normal and immortalized human fibroblasts . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Alterations in hepatic cdk 1 , cdk 2 , cdk 4 , cdk 5 , and cyclin protein expression were determined in response to acute dosing of the prototypic peroxisome proliferator and hepatocarcinogen [ 4 chloro 6 ( 2 , 3 xylidino ) 2 pyrimidinylthio ] acetic acid ( WY 14 , 643 ) . ^^^ The largest relative increases , 6 . 1 , 2 . 8 , 11 , 83 , and 7 . 9 fold , were seen with cdk 1 , cdk 4 , cyclin B , cyclin D 3 , and PCNA , respectively . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression of p 16 in these cells results in sequestering of cdk 4 and cdk 6 , rendering cyclin D1 / cdk complexes inactive . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although the abundance of cyclin D 1 , Cdk 4 , and Cdk 6 did not decrease cyclin D 1 associated kinase activity was reduced by approximately 50 % at 9 18 h . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 was dominant among the D type cyclins , formed abundant complexes with cyclin dependent kinase ( Cdk ) Cdk 4 rather than Cdk 6 , and the immunoprecipitated cyclin D1 / Cdk4 holoenzyme was active as a pRB kinase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , inostamycin also inhibited cyclin D 1 expression induced by serum ; and consequently , hyperphosphorylation of retinoblastoma protein ( pRB ) by RB kinases such as CDK 4 and CDK 2 was abolished , which would result in elimination of functional inactivation of pRB . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ang 2 activated cdk 4 and caused phosphorylation of pRb , peaking at 12 hours , but subsequently downregulated cyclin D 1 , D 3 , and A expression and cdk 2 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These data strongly support the idea that deregulation of the CDK4 / cyclin D pathway , via CDKN 2 or CDK 4 mutations , is of biological significance in the development of melanoma . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In a yeast two hybrid assay , cyclin A 1 can bind to CDK 2 but not to CDC 2 , CDK 4 , and CDK 5 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In dividing cells , p 27 ( Kip 1 ) is predominantly bound to cyclin D cdk 4 without inhibiting this kinase . ^^^ In vitro , however , p 15 prevents p 27 binding only if it has access to cyclin D cdk 4 first . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
B cells receiving a complete growth stimulus express cyclin D 2 by 10hr and cyclin E by 10 24hr poststimulation while increasing their protein levels of cdk 4 and cdk 2 . ^^^ In the absence of cyclin D 2 accumulation , cdk 4 is not activated , and cyclin E is not expressed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We report here that administration of 17 beta estradiol ( E 2 ) to adult ovariectomized rats induces within the first 25 h significant activation of cdk 4 , 5 , and 6 , but not cdk 2 , in the uterus , accompanied by increased expression of D type ( D 1 3 ) , A and E cyclin messenger RNAs ( mRNAs ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of cyclins ( A , B 1 , D 1 , D 3 , E ) , cyclin dependent kinases ( CDK 2 ( 3 ) , CDK 4 ) , and the cyclin dependent kinase inhibitors ( CDKIs ) p 16 ( INK4A ) and p 21 ( CIP 1 ) was studied in 9 malignant human astrocytoma cell lines using northern blot analysis , immunocytochemistry , and immunoblotting to see if their altered expression contributed to astrocytoma proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the GCT cell lines in which cyclin D 2 was highly expressed , cyclin D 2 was in complex with its expected catalytic partners ( Cdk 4 and Cdk 6 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although the cell cycle of the rat fibroblast cell line , 3Y1 , was arrested in quiescence by contact inhibition , the Cdk 4 bound to its regulatory subunit , cyclin D 1 or D 3 . ^^^ Phosphorylation of the cyclin D 1 bound Cdk 4 by the Cdk activating kinase could convert the inactive cyclin D 1 Cdk4 complex into its active form in vitro , suggesting that threonine 172 of the Cdk 4 , of which phosphorylation is required for its activation , was in part unphosphorylated in contact inhibited 3Y1 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
SNAP inhibited the activity of cyclin dependent kinase 2 ( Cdk 2 ) and phosphorylation of the retinoblastoma protein , both of which usually increased from about 9 h , whereas it did not inhibit the activities of cyclin D associated kinase ( s ) , Cdk 4 , and Cdk 6 , which normally increased from 0 3 h . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Estrogen induced activation of Cdk 4 and Cdk 2 during G 1 S phase progression is accompanied by increased cyclin D 1 expression and decreased cyclin dependent kinase inhibitor association with cyclin E Cdk 2 . ^^^ Entry into S phase was preceded by increased activity of both Cdk 4 and cyclin E Cdk 2 and hyperphosphorylation of pRB , all within the first 3 6 h of estradiol treatment . ^^^ The increase in Cdk 4 activity was accompanied by increases in cyclin D 1 mRNA and protein , indicating that an initiating event in the activation of Cdk 4 was increased cyclin D 1 gene expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
OBJECTIVE : The recently cloned gene p 16 ( MST 1 ) has been identified as a putative tumor suppressor gene that binds to CDK 4 and CDK 6 ( cyclin dependent kinases ) , preventing their interaction with cyclin D 1 and thereby preventing cell cycle progression at the G 1 stage . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Exposure to hormones via a pituitary isograft stimulated the synthesis of cyclin D 1 and D 2 but not D 3 associated to cdk 4 as well as total cdk 4 proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In agreement with our other data , cyclin D 1 and p 21 bind concomitantly to cdk 4 during the in vivo assembly of cdk4 / cyclin D 1 complexes . ^^^ Finally , we find that all three CIP / KIP inhibitors target cdk 4 and cyclin D 1 to the nucleus . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Transforming growth factor beta stabilizes p15INK4B protein , increases p15INK4B cdk 4 complexes , and inhibits cyclin D 1 cdk4 association in human mammary epithelial cells . ^^^ As cdk 4 and cdk 6 associated p15INK4B increased during TGF beta arrest of sensitive cells , there was a loss of cyclin D 1 , p21Cip1 , and p27Kip1 from these kinase complexes , and cyclin E cdk 2 associated p27Kip1 increased . ^^^ In HMEC , p15INK4B complexes did not contain detectable cyclin . p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D 1 , p21Cip1 , and p27Kip1 from cdk 4 isolated from sensitive cells . ^^^ Cyclin D 1 could not be displaced from cdk 4 in the resistant 184A1L5R cell lysates . ^^^ Furthermore , p27Kip1 binding shifts from cdk 4 to cyclin E cdk 2 during TGF beta mediated arrest . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 in cooperation with its major catalytic partners , cyclin dependent kinases cdk 4 and cdk 6 , facilitates progression through the G 1 phase of the eukaryotic cell cycle , in part through phosphorylation of the retinoblastoma protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These stimulations were associated with a decrease in cyclin dependent kinase ( cdk ) 2 level , whereas cdk 4 and cdk 6 remained unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of D type G 1 cyclins and their assembly with their catalytic partners , the cyclin dependent kinases 4 and 6 ( CDK 4 and CDK 6 ) , into active holoenzyme complexes are regulated by growth factor induced signals . ^^^ Although `` free ' ' or CDK 4 bound cyclin D 1 molecules are intrinsically unstable ( t1 / 2 < 30 min ) , a cyclin D 1 mutant ( T286A ) containing an alanine for threonine 286 substitution fails to undergo efficient polyubiquitination in an in vitro system or in vivo , and it is markedly stabilized ( t1 / 2 approximately 3 . 5 hr ) when inducibly expressed in either quiescent or proliferating mouse fibroblasts . ^^^ Phosphorylation of cyclin D 1 on threonine 286 also occurs in insect Sf 9 cells , and although the process is enhanced significantly by the binding of cyclin D 1 to CDK 4 , it does not depend on CDK 4 catalytic activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cells lacking functional pRb expressed p 16 , instead of forming cyclin D / CDK 4 complex . ^^^ In the LNCaP prostatic cancer cell line , however , both p16 / CDK4 and cyclin D / CDK 4 complexes were present independently , probably because of partial loss of pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here , we show that 8Br cAMP strongly blocks both the growth factor induced increase in cyclin D 1 protein expression and decrease in p 27 ( KIP 1 ) protein levels , leaving untouched the levels of cyclin D 3 , cdk 2 and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cdc 37 is not an inhibitor nor an activator of the Cdk4 / cyclin D 1 kinase , while it appears to facilitate complex assembly between Cdk 4 , and cyclin D 1 in vitro . ^^^ Cdc 37 competes with p 16 for binding to Cdk 4 , suggesting that p 16 might exert part of its inhibitory function by affecting the formation of Cdk4 / cyclin D 1 complexes via Cdc37 . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
ILK overexpression results in increased expression of cyclin D 1 , activation of Cdk 4 and cyclin E associated kinases , and hyperphosphorylation of the retinoblastoma protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
GR activation in U2OS cells represses expression of the cyclin dependent kinases ( CDKs ) CDK 4 and CDK 6 as well as their regulatory partner , cyclin D 3 , leading to hypophosphorylation of the retinoblastoma protein ( Rb ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Differential effects were observed with the G 1 cell cycle mediators CDK 4 , CDK 5 , and cyclin D 3 , p21Waf1 and p27Kip1 CDK inhibitory protein concentrations rose in accordance with the induction of DNA synthesis and histone H 1 kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 overexpression resulted in a concomitant increase in CDK 4 levels in the adult myocardium , as well as modest increases in proliferating cell nuclear antigen and CDK 2 levels . ^^^ Cyclin D 1 overexpression resulted in a concomitant increase in CDK 4 levels in the adult myocardium , as well as modest increases in proliferating cell nuclear antigen and CDK 2 levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 2 activates Cdk 2 in preference to Cdk 4 in human breast epithelial cells . ^^^ The cyclin D 2 associated kinase activity was largely inhibited by Cdk 2 specific inhibitors and could phosphorylate histone H 1 , a substrate for Cdk 2 but not for Cdk 4 and Cdk 6 . ^^^ In contrast , Cdk 4 and Cdk 6 were predominantly responsible for cyclin D 1 associated kinase activity as previously reported . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Serine 795 is phosphorylated efficiently by Cdk 4 , even in the absence of an intact LXCXE motif in cyclin D , but not by Cdk 2 or Cdk 3 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In cells of higher eukaryotes , cyclin D dependent kinases Cdk 4 and Cdk 6 and , possibly , cyclin E dependent Cdk 2 positively regulate the G 1 to S phase transition , by phosphorylating the retinoblastoma protein ( pRb ) , thereby releasing E2F transcription factors that control S phase genes . ^^^ We demonstrate that ectopic expression of cyclin E , but not cyclin D 1 , can override G 1 arrest imposed by either the p16INK4a Cdk inhibitor specific for Cdk 4 and Cdk 6 or a novel phosphorylation deficient mutant pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
EGF alone stimulated proliferation of PC 12 cells and increased the levels of several cell cycle progression factors including cdk 2 , cdk 4 , and cyclin B 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mammalian D type cyclins are differentially expressed during the first gap phase ( G 1 ) of the cell cycle in various cell types , and function as regulatory subunits of cyclin dependent kinases ( cdks ) , cdk 4 and cdk 6 , to form holoenzymes whose activities are both necessary and rate limiting for G 1 progression . ^^^ Mitogenic signals induce the expression of cyclin D and cdk 4 proteins , and facilitate their assembly into holoenzymes and their post translational modification , while anti proliferative stimuli extinguish the activity of cyclin D dependent kinases by inducing cdk inhibitors which directly interfere with their catalytic functions and / or inhibit the post translational activation of cyclin bound cdks . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although rat fibroblast cell line , 3Y1 , arrested in quiescence by contact inhibition , Cdk 4 bound its regulatory subunit , cyclin D 1 or D 3 . ^^^ Phosphorylation of the cyclin D 1 bound Cdk 4 by Cdk 4 activating kinase , composed of cyclin H and MO 15 ( alias Cdk 7 ) , which was reconstituted in Spodoptera frugiperda cells ( Sf 9 ) could convert inactive cyclin D 1 Cdk4 complex into active form in vitro , suggesting that threonine 172 in the Cdk 4 , whose phosphorylation is required for its activation , was in part unphosphorylated in the contact inhibited 3Y1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of expression of genes regulating Rb phosphorylation revealed that activin A suppressed cyclin D 2 , the sole D type cyclin gene expressed in the hybridoma cells , and activated p21CIP1 / WAF1 but had no effect on expression of cyclin dependent kinases ( CDK 2 , CDK 4 , CDK 6 ) and other CDK inhibitors ( p27KIP1 , p16INK4a , p15INK4b ) . ^^^ Modulation of cyclin D 2 and p21CIP1 / WAF1 expression resulted in a decrease in level of cyclin D 2 CDK4 complex and an increase in level of CDK 4 complexed with p21CIP1 / WAF1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Complexes of cdk 4 with cyclin D 1 or cdk 2 with cyclin E or A can activate the cyclin B 1 promoter , and activation is uniquely dependent on the CCAAT elements in both normal and heterologous contexts . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunoblots utilizing an antibody against the 110 kDa retinoblastoma protein ( Rb ) , a downstream phosphorylation target of the cyclin D1 / cyclin dependent kinase 4 ( cdk 4 ) complex , showed reduced electrophoretic mobility of this protein as early as 8 h after PDGF treatment , suggesting phosphorylation of Rb by the cyclin D1 / cdk4 dimer in vivo . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cell cycle regulatory molecules were analysed in normal human endometrial tissue using antibodies against cyclins D 1 , E , A , and B 1 and cyclin dependent kinases ( CDKs ) cdk 4 , cdk 2 , and cdc 2 . ^^^ Cyclin E , cdk 2 and / or cdk 4 were especially apparent in the cytoplasm of most of the gland cells as well as in the stromal cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of BIP with cyclins / CDKs and E2F antisera indicated association with cdc 2 , cdk 2 , cdk 4 , cyclin B , cyclin D , cyclin A and E2F 4 but not with cdk 3 , cdk 5 , cdk 6 , E2F 1 , E2F 2 , E2F 3 , E2F 5 and cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mutual requirement of CDK 4 and Myc in malignant transformation : evidence for cyclin D1 / CDK4 and p16INK4A as upstream regulators of Myc . ^^^ We demonstrate that both cyclin D 1 and CDK 4 functionally depend on active Myc to exert their potential as oncogenes and vice versa that the transforming ability of Myc requires functional cyclin D / CDK complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In human cells transformed by the large T antigen of simian virus 40 ( SV 40 T Ag ) and human tumour cell lines that lack a functional retinoblastoma gene product ( pRb ) no cyclin D 1 Cdk4 complexes can be detected because all the available Cdk 4 is associated with the Cdk inhibitor p16INK4a . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Assay for activity of mammalian cyclin D dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , KCl significantly reduced the EGF induced expression of cell cycle progression factors cdk 2 , cdk 4 , cyclin B 1 and PCNA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RA did not affect cyclins D 1 , A , and E and cyclin dependent kinase 2 ( CDK 2 ) expression , but significantly reduced cyclin D 3 and CDK 4 expression after 24 h . ^^^ Cyclin D 3 and CDK 4 are likely the early targets of RA , followed by reduced pRB expression and phosphorylation , as well as by the inhibition of the E2F1 transcription factor which controls progression from G 1 to S phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We find that human Myt 1 phosphorylates and inactivates Cdc 2 containing cyclin complexes but not complexes containing Cdk 2 or Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Evaluation of the activity of cyclin CDK complexes showed that activation of cyclin D CDK 4 was not modified by dexamethasone . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunodepletion revealed this kinase activity could be abolished by removal of either cyclin A or Cdk 2 but was unaffected by removal of Cdk 4 or any D type cyclin . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We investigated the expression of cyclin D 1 and its kinase , cdk 4 , after induction of focal cerebral ischemia in the rat . ^^^ Double staining for DNA fragmentation detection ( TUNEL ) and expression of cyclin D 1 and cdk 4 also was performed . ^^^ Cyclin D 1 and cdk 4 were selectively expressed in morphologically intact or altered neurons and oligodendrocytes localized to the ischemic tissue . ^^^ Apoptotic cells were not immunoreactive to cyclin D 1 and cdk 4 at 46 hours after 2 hours of middle cerebral artery occlusion . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As the PI increased , the mRNA and protein levels of cyclins D 1 , D 3 and B , the mRNA levels of cyclin A , the protein levels of CDK 4 and CDK 2 , and the activities of CDKs ( CDK 4 , CDK 2 and cdc 2 ) increased in the outer medullae of kidneys after ischemic injury . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Altered expression of cyclin D 1 and CDK 4 genes in ovarian carcinomas . ^^^ We analyzed the expression and amplification of cyclin D 1 and CDK 4 genes in ovarian carcinomas . ^^^ Northern blot analysis revealed overexpression of cyclin D 1 in 12 of 65 ( 18 % ) ovarian carcinomas while CDK 4 was overexpressed in 7 of 48 cases ( 14 % ) . ^^^ Overexpression of cyclin D 1 and CDK 4 transcripts was correlated , suggesting a role of both genes in altered growth control of ovarian cancer cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Moreover , the chimeric GST ICP 0 ( exon 2 ) protein shown to bind cyclin D 3 had no effect on the activity of the kinase on GST pRb when added to mixtures of lysates of Sf 9 cells which coexpressed cyclin D 3 and CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We used double staining histochemistry to investigate the relationship between apoptotic cell death and selective protein expression associated with DNA damage ( p 53 , Bax , MDM 2 , Gadd 45 ) , DNA repair ( PCNA ) and cell cycle proteins ( cyclin A , cyclin D , cdk 2 , cdk 4 ) in rats ( n = 6 ; control rats , n = 5 ) subjected to transient ( 2 h ) middle cerebral artery occlusion ( MCAo ) and 46 h of reperfusion . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The MadMyc induced G 1 arrest is rescued by ectopic expression of cyclin E / CDK2 and cyclin D1 / CDK 4 , but not by Cdc25A , a known cell cycle target of c Myc . ^^^ MadMyc does not cause alterations in the expression levels of cyclin E , CDK 2 , p27kip1 , cyclin D 1 or CDK 4 in G 1 arrested cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although p 27 ( Kip 1 ) has been considered a general inhibitor of G 1 and S phase cyclin dependent kinases , we report that the interaction of p 27 with two such kinases , cyclin A Cdk 2 and cyclin D Cdk 4 , is different . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Germline mutations in CDKN 2 on chromosome 9p21 , which codes for the cyclin D kinase inhibitor p 16 , and more rarely , mutations in the gene coding for CDK 4 , the protein to which p 16 binds , underlie susceptibility in some melanoma families . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Whereas the level of expression and activity of cyclin D 1 and its associated kinase , cdk 6 , was modest in tumor cells , both cyclin A and E , and their kinase partners , cdk 2 and cdk 4 , were highly expressed and exhibited significant kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Reverse transcription polymerase chain reaction ( RT PCR ) analysis indicated that TGF beta 1 mediated G 1 arrest correlated with the down regulation of cdk 4 , cdk 6 and cyclin D 2 , and that abrogation of TGF beta 1 mediated G 1 arrest by GM CSF correlated with the constitutive over expression of cyclin D 2 and cdk 6 but not cdk 4 . ^^^ These results suggest the importance of cyclin D2 / cdk6 levels in abrogating G 1 arrest in cells exposed to TGF beta 1 , and raise the possibility that the GM CSF mediated up regulatory pathway of signal transduction through cyclin D2 / cdk6 differs from the TGF beta 1 cdk 4 mediated pathway in SKM 1 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In mammalian cells , the G1 / S specific CDK activities are composed of complexes between D type cyclins and either CDK 4 or CDK 6 and between cyclin E ( and possibly cyclin A ) and CDK 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To investigate the role of these cyclins in neuronal differentiation , we used a conditionally immortalized rat hippocampal cell line , H 19 7 , that expresses cyclin dependent kinases 4 and 5 ( cdk 4 and 5 ) . ^^^ Cyclin D 1 , which activates cdk 4 and binds but does not activate cdk 5 , was increased upon differentiation of the H 19 7 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mutations in Rb , cyclin D 1 , its catalytic subunit Cdk 4 , and the CDKI p16Ink4a , which alter the protein or its level of expression , are all strongly implicated in cancer . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Prognostic implications of cyclins ( D 1 , E , A ) , cyclin dependent kinases ( CDK 2 , CDK 4 ) and tumor suppressor genes ( pRB , p16INK4A ) in childhood acute lymphoblastic leukemia . ^^^ Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias ( ALL ) for their expression of cyclins ( D 1 , E , A ) , cyclin dependent kinases ( cdk 2 , cdk 4 ) and tumor suppressor genes ( pRb , p16INK4A ) , in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL . ^^^ This investigation demonstrated that cyclin D 1 and cdk 4 were the most important prognostic factors for children with ALL , and that the combination of them showed the strongest prognostic relevance . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of pRb , cyclin D 1 and its catalytic subunit , Cdk 4 , was studied by immunohistochemistry and immunoblotting . ^^^ However , co immunoprecipitation of Cdk 4 with cyclin D 1 revealed low levels of cyclin D / Cdk4 complex ; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , cdk 4 and the tumour suppressors p 16 and retinoblastoma protein ( pRb ) are thought to comprise a linked system governing cell passage through the G 1 phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We further found that reentry into the cell cycle upon loss of TSC 2 is dependent on the activity of the G 1 cyclin dependent kinases ( CDKs ) , Cdk 2 or Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The pRB E2F interaction is , in turn , regulated by a pathway that includes cyclin D 1 , cdk 4 , and p 16 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The passage of mammalian cells through the restriction point into the S phase of the cell cycle is regulated by the activities of Cdk 4 and Cdk 6 complexed with the D type cyclins and by cyclin E / Cdk2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of several cell cycle regulating proteins , including cyclin A , the cyclin dependent kinases ( cdk ) 2 and cdk 4 , in addition to cyclin D 1 itself , was markedly decreased . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A mathematical model integrating the roles of cyclin D , cdk 4 , cyclin E , cdk 2 , E2F and RB in control of the G 1 phase of the cell cycle is described . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast to other studies , over expression of cyclin D 1 , a regulatory subunit of CDK 4 and 6 , was not observed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The pRB cell cycle regulatory cascade is frequently perturbed in neoplasia by overexpression of a component of the pRB phosphorylating cyclin D1 / CDK4 complex or by inactivation of pRB or the CDK 4 inhibitors p 16 and p 15 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The salt eluates were examined for the presence of both DNA replication proteins ( Pol alpha , delta , straightepsilon , PCNA , RFC , RFA , DNA ligase 1 , NDH 2 , Topo 1 and Topo 2 ) and cell cycle proteins ( Cyclins A , B 1 , D 1 , D 2 , D 3 , E , CDK 2 , CDK 4 , CDK 5 and p 21 ) by western blotting with specific antibodies . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Malignant transformation by cyclin E and Ha Ras correlates with lower sensitivity towards induction of cell death but requires functional Myc and CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To further investigate the cell cycle regulation , cell cycle controlling factors , such as the retinoblastoma gene product ( pRB ) and its regulatory components cdk 2 , cdk 4 , and cyclin D 1 , were analyzed by Western immunoblots . ^^^ Western blots further showed that BFA induced dephosphorylation of pRB accompanied by down regulation of cdk 2 , cdk 4 , and cyclin D 1 expression . ^^^ CONCLUSION : These results suggest that BFA may be a potent cell cycle modulator , which post translationally regulates pRB phosphorylation possibly by down regulating cdk 2 , cdk 4 , and cyclin D 1 and / or by up regulating a phosphatase ( s ) capable of dephosphorylating pRB . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These results indicate that serum deprivation and contact inhibition have different mechanisms although they affect the same pathway cyclin D cdk 4 , pRB , cyclin E cdk2 . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The Rb cyclin D pathway was analyzed by studying the pRb protein , the p16MTS1 gene , cyclin D 1 , cyclin D 3 , p27Kip1 , cdk 4 , and cdk 6 proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Hence , both the cyclin D 1 and D 3 as well as CDK 4 and CDK 6 subunits can confer substrate specificity on the overall cyclin D CDK complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We studied the immunolocalization of cyclins D 1 and E and their corresponding partner cyclin dependent kinases ( cdk ) , cdk 4 and cdk 2 in 41 cases of human breast malignancy ( 21 invasive ductal carcinomas and 19 invasive lobular carcinomas ) and examined the correlation of the labeling indexes among these cyclins , cdks , Ki 67 , estrogen receptor ( ER ) and progesterone receptor ( PR ) . ^^^ Immunoreactivity for cyclin E and cdk 2 was detected in all the cases and observed in the nuclei of both carcinoma and non carcinoma cells . cdk 4 immunoreactivity was detected in 39 / 41 ( 95 % ) cases and found in carcinoma and non carcinoma cells . ^^^ However , when examining only invasive ductal carcinomas , a significant correlation was detected between Ki 67 and cyclin D 1 ( p = 0 . 0069 ) , Ki 67 and cdk 2 ( p = 0 . 0043 ) and cyclin D 1 and cdk 4 ( P = 0 . 0024 ) . ^^^ Cyclin D 1 and cdk 2 expression correlated with cell proliferation ( Ki 67 ) and cyclin D 1 expression with expression of cdk 4 in invasive ductal carcinoma but not invasive lobular carcinoma . ^^^ These results also indicate different patterns of cyclin D 1 , cyclin E , cdk 2 and cdk 4 expression between invasive ductal and lobular carcinoma of human breast . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclin D 1 , CDK 4 and p27KIP1 is associated with the p16MTS1 gene status in human esophageal carcinoma cell lines . p16MTS1 / INK4A negatively regulates cell cycle progression by inhibiting the cyclin D / CDK4 complex that phosphorylates pRb . ^^^ All the p 16 negative cell lines expressed high levels of cyclin D 1 , CDK 4 and p27KIP1 proteins . ^^^ Interestingly , the expression level of cyclin D 1 was closely correlated to the levels of not only CDK 4 but also p27KIP1 protein in p 16 negative cell lines . ^^^ These results suggest that the expression of cyclin D 1 , CDK 4 , Rb and p 27 is associated with the p 16 gene status in esophageal carcinoma cell lines . ^^^ Alternatively , loss of the p 16 gene and subsequent over expression of cyclin D 1 and CDK 4 might be involved in autonomous growth of esophageal carcinoma cells . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In mammalian cells , the G 1 phase progression is controlled by the serial activation of several cyclin dependent kinases ( Cdks ) , starting with Cdk 4 and Cdk 6 . ^^^ The suppression of Tax synthesis , however , resulted in a significant reduction of the Cdk 4 and Cdk 6 activities but did not influence the expression of Cdk 4 , Cdk 6 , or cognate D type cyclin proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of a cyclin D 1 mutant and a dominant negative CDK 4 mutant implied that this repression is independent of complex formation with a CDK partner . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Tyr Phe limitation progressively decreased cyclin D 1 expression to 30 % of control within four days and did not affect expression of cyclin D 3 or cyclin dependent kinase ( CDK 2 , CDK 4 , and CDK 5 ) expression , Met limitation decreased cyclin D 3 expression to 25 % of control and CDK 2 expression to 32 % of control by Day 4 and did not affect expression of cyclin D 1 , CDK 4 , and CDK 5 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Treatment with alpha 5 monoclonal antibody led to a marked increase in the expression of CDK 4 in G 1 phase of the cell cycle and consequently increased the phosphorylation of retinoblastoma protein . alpha 5 monoclonal antibody treatment increased both cyclin A and cyclin E associated kinase activity which was accompanied by increased protein levels of CDK 2 and cyclin A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As to expression of the other cell cycle related proteins , cyclin A , cyclin D 1 , CDK 2 or CDK 4 , no significant difference was detected among the 12 cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have previously shown that a 20 amino acid peptide derived from the third ankyrin like repeat of the p16CDKN2 / INK4a ( p 16 ) tumour suppressor protein ( residues 84 103 of the human p 16 protein ) can bind to cdk 4 and cdk 6 and inhibit cdk 4 cyclin D 1 kinase activity in vitro as well as block cell cycle progression through G 1 . ^^^ A deletion series of the p 16 derived peptide shows that a 10 residue peptide still retains cdk 4 cyclin D 1 kinase and cell cycle inhibitory activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Compared with control animals , animals treated with 2 AAF showed increased levels of cdk 4 and cyclin D 3 from 12 and 15 hours after PH , respectively , and altered cyclicity in cyclin D 3 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This study examined the involvement of D type G 1 cyclins and their associated cyclin dependent kinase ( cdk 4 ) in the cAMP dependent G 1 phase progression of dog thyroid cells . ^^^ It was found to reflect both the unmasking of an epitope of cyclin D 3 close to its domain of interaction with cdk 4 , and the nuclear translocation of cyclin D 3 . ^^^ TSH and EGF+serum also induced a previously undescribed nuclear translocation of cdk 4 , the assembly of precipitable cyclin D 3 cdk4 complexes , and the Rb kinase activity of these complexes . ^^^ The present study ( a ) provides the first example in a normal cell of a stimulation of G 1 phase progression occurring independently of an enhanced accumulation of cyclins D , ( b ) identifies the activation of cyclin D 3 and cdk 4 through their enhanced assembly and / or nuclear translocation , as first convergence steps of the parallel cAMP dependent and growth factor mitogenic pathways , and ( c ) strongly suggests that this new mechanism is essential in the cAMP dependent mitogenesis , which provides the first direct demonstration of the requirement for cyclin D 3 in a G 1 phase progression . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Aberrant expression of cyclin D , cdk 4 , proliferating cell nuclear antigen , and cyclin B 1 were identified in the hippocampus , subiculum , locus coeruleus , and dorsal raphe nuclei , but not inferotemporal cortex or cerebellum of AD cases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This was accompanied by decreases in the expression of cyclins D 1 , D 3 , and E , decreased abundance of cyclin D 1 and cyclin D 3 Cdk4 complexes , increased association of the cyclin dependent kinase ( CDK ) inhibitor p 27 with the remaining Cdk 4 complexes , and changes in the molecular masses and compositions of cyclin E complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin D 3 , a major component of the cyclin dependent kinase ( CDK ) activity required for pRb phosphorylation , was completely abrogated by MPA treatment of T cells activated by interleukin 2 ( IL 2 ) and leucoagglutinin ( PHA L ) , whereas the expression of cyclin D 2 , CDK 6 , and CDK 4 was more mildly attenuated . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mechanistically , we have found that cyclin dependent kinase 2 ( CDK 2 ) and the cyclin E associated kinase ( largely CDK 2 ) , but not CDK 4 , in the G 1 phase were strongly inhibited by LAC . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The interplay among G 1 cyclins ( D type cyclins and cyclin E ) , cyclin dependent kinases ( cdk 4 , 6 , and 2 ) , cdk inhibitors , and protein phosphatases determines the phosphorylation state of the pocket proteins which in turn regulates the ability of the pocket proteins to complex with E2F . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
After PH in BALB / c mice , p 21 was induced during the prereplicative ( G 1 ) phase and was maximally expressed after peak hepatocyte DNA synthesis . p 27 was present in quiescent liver and was minimally induced after PH . p 21 and p 27 immunoprecipitated with CDK 2 , CDK 4 , and cyclin D 1 in the regenerating liver . ^^^ The activity of CDK 2 , CDK 4 and cyclin D 1 associated kinases was upregulated after PH , and maximal activity of these enzyme complexes corresponded to peak DNA synthesis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The Trypanosoma cruzi immunosuppressive factor ( TIF ) targets a lymphocyte activation event subsequent to increased intracellular calcium ion concentration and translocation of protein kinase C but previous to cyclin D 2 and cdk 4 mRNA accumulation . ^^^ In contrast , the mRNA levels of cyclin D 2 and cdk 4 , which form a holoenzyme complex known to regulate cell progression through the G 1 phase , were markedly reduced by TIF . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RESULTS : Alterations were observed in the expression of cylins D 1 and E in the transformed cells , whereas the amounts of the cyclin dependent kinases ( CDKs ) CDK 2 and CDK 4 were almost identical in both cell types . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 2 was also found to be associated with the cyclin dependent kinases CDK 2 and CDK 4 but not CDK 6 during growth arrest . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The protein levels of cyclin dependent kinase 2 ( cdk 2 ) and cdk 4 were unaffected during this G 1 arrest and the total cellular levels of the cdk inhibitors p21cip1 and p27kip1 were not increased . ^^^ Instead , the cdk 4 activity decreases resulting from KN 93 were the result of a 75 % decrease in cyclin D 1 levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 , CDK 4 , and CDK 6 involved in G 1 phase control were significantly decreased under dexamethasone treatment whatever the level of stimulation of lymphocytes ( stimulated or unstimulated PBL ) . ^^^ The protein analysis pinpoints the major complexes concerned : CDK 4 and CDK6 / cyclin D are mainly involved in G 1 phase modifications , while CDK 2 and its partner , cyclin E , might be specifically involved in the lengthening of S phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In two of these 43 cases , homozygous deletions of CDKN2A were detected along with a CDK 4 mutation or amplification of the cyclin D 1 ( CCND 1 ) gene . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The accumulation of cells in G 1 was associated with decreased levels of expression of cyclin D 1 but no effect was seen on the expression of CDK 4 or the immediate early response gene c jun . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The addition of CaM inhibitors to cultures of proliferating NRK cells blocked the activity of the cyclin dependent protein kinases 4 ( cdk 4 ) and 2 ( cdk 2 ) , which are enzymes implicated in the progression of G 1 and in the onset of DNA replication , respectively . ^^^ CaM modulates the activity of cdk 4 by regulating the nuclear location of both cdk 4 and cyclin D , its associated regulatory subunit . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The overall effect of rapamycin on cyclin D 1 leads , in turn , to impaired formation of active complexes with Cdk 4 , a process which triggers retargeting of the p 27 ( Kip 1 ) inhibitor to cyclin E / Cdk2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blotting disclosed that G CSF treatment resulted in down regulation of cyclin D 2 and cdk 2 and up regulation of cyclin D 1 and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Defining the minimal portion of the retinoblastoma protein that serves as an efficient substrate for cdk 4 kinase / cyclin D 1 complex . ^^^ We have determined the minimal portion of the retinoblastoma protein ( Rb ) that can serve as an efficient substrate for in vitro phosphorylation by cdk 4 kinase D 1 cyclin . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cyclin dependent kinase ( CDK ) inhibitor p 18 blocks progression of the cell cycle by associating with the cyclin D dependent kinases CDK 6 and CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cell death in vitro was preceded by upregulation of cyclin D 1 , cdk 4 , and increased phosphorylation of retinoblastoma protein ; all are indicators of cell cycle advancement . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the search for new risk factors at the molecular and cellular levels , clinical data [ lymph node involvement ( LN ) and stage ] were used and 104 squamous cell lung carcinomas were analyzed by immuno histochemistry for expression of cyclin D 1 , cyclin A , cdk 2 , cdk 4 , RB , and E2F1 . ^^^ The results of the univariate analysis of all 8 factors showed that cyclin A and cdk 2 gave the best prognostic information , while no prognostic value could be found associated with cyclin D 1 , cdk 4 , RB and E2F1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To test this hypothesis , a recently developed quantitative reverse transcriptase polymerase chain reaction method was used to assess simultaneously expression of 15 genes mechanistically associated with cell cycle control ( c myc , E2F 1 , p 21 , rb , PCNA , cyclin D 2 , cyclin D 3 , cyclin E , cdc 2 , CDK 2 , CDK 4 , mad , max p 21 , max p 22 , and p 53 ) in normal cell cultures from five individuals and in nine different malignant BEC lines . ^^^ Relative to the mean expression levels in cultured normal cell populations , expression of c myc , E2F 1 , PCNA , cyclin E , and CDK 4 messenger RNA ( mRNA ) were significantly increased and expression of p 21 and p 53 mRNA were significantly decreased in one or two , but not all three subtypes ( squamous , adenocarcinoma and small cell ) of carcinoma cell lines evaluated . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The protein levels of cyclin dependent kinase ( Cdk ) 2 , Cdk 4 and Cdk 6 are not altered in the resistant sublines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The resulting growth inhibitory effect of HMBA was completely reversible and was analyzed in terms of percent cells in G 1 ; association of D type cyclins with cyclin dependent kinase ( cdk ) 4 and cdk 6 ; G 1 kinase activity ; association of retinoblastoma protein ( pRb ) and phosphorylated pRb with D type cyclins ; and association of p16INK4a , p15INK4b , and p27Kip1 with cdk 4 and cdk 6 . ^^^ The data suggest that HMBA induced growth inhibition is due to multifactorial mechanisms involving decreases in total cyclin D 1 and inhibition of cdk 4 and cdk 6 kinase activities through elevation of levels of cdk 4 and cdk 6 associated p27Kip1 and concomitant increases in hypophosphorylated pRb and stable cyclin D2 / pRb and cyclin D3 / pRb complexes that help maintain pRb in a functional state . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of cell lysates from untreated or TGF beta treated cultures showed no alterations in expression of CDK 2 , CDK 4 , CDK 6 or cyclin E in cell lines which were either sensitive ( HaCaT , HN 6 ) or refractory ( HN 12 , HN 30 ) to the growth inhibitory effects of TGF beta . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin D 1 , cdk 4 , p16INK4a , and Rb protein was examined by immunohistochemistry in 4 ( methylnitrosamino ) 1 ( 3 pyridyl ) 1 butanone ( NNK ) induced mouse lung tumors . ^^^ Immunohistochemical staining revealed exclusive nuclear staining of both cyclin D 1 and cdk 4 that was light to moderate in normal mouse lung tissues , but intense in lung adenomas and adenocarcinomas . ^^^ Western blot analysis confirmed the increased expression of cyclin D 1 and cdk 4 in lung tumors compared to normal lung . ^^^ These results suggest that alterations in the cell cycle proteins , cyclin D 1 , cdk 4 , p16INK4a , and Rb , may play a role in the acquisition of autonomous growth by adenomas . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 expression was absent despite high levels of CDK 4 and CDK 6 , and the CKI p 27 was expressed in chondrocytes , osteoclasts , and at lower levels in osteoblasts . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In non tumorigenic mouse liver cells cyclin D 1 associated with CDK 6 , CDK 4 or CDK 2 to form binary ( cyclin D 1 CDK ) , tertiary ( cyclin D 1 CDK p27KIP1 ) or quaternary ( cyclin D 1 CDK p21WAF1 PCNA ) complexes . ^^^ In MC transformed cells formation of various binary , tertiary and quaternary cyclin D 1 CDK ( CDI ) protein complexes was reduced , resulting in decreased CDK 4 kinase activity . ^^^ In MNNG transformed cells select cyclin D 1 CDK6 CDI and cyclin D 1 CDK2 CDI protein complexes were altered but CDK 6 and CDK 4 kinase activity remained unaffected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
There was no apparent relationship , however , between cyclin D 1 expression and the in vitro activity of its major kinase partner , Cdk 4 , although MDA MB 134 cells displayed the highest level of both cyclin D 1 expression and Cdk 4 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Inducible expression of either c Myc or cyclin D 1 was sufficient for S phase entry in cells previously arrested in G 1 phase by pretreatment with ICI 182780 , a potent estrogen antagonist . c Myc expression was not accompanied by increased cyclin D 1 expression or Cdk 4 activation , nor was cyclin D 1 induction accompanied by increases in c Myc . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We studied the immunolocalization of cyclins D 1 and E and their corresponding partner cyclin dependent kinases ( cdk ) , cdk 4 and cdk 2 in 39 cases of human endometrioid endometrial carcinoma and examined the correlations between the labeling indexes of the cyclins , cdks and clinicopathologic parameters and the clinical outcome of the patients . ^^^ Immunoreactivity for cyclin E , cdk 2 , and cdk 4 was detected in carcinoma cells of 37 / 39 ( 95 % ) , 39 / 39 and 36 / 39 cases , respectively . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A co precipitation study showed that in cells treated with gamma LA there was an increase in the binding of these inhibitors with CDK 4 , CDC 2 , and cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Since we found that the p 27 ( kip 1 ) activity was dependent on cyclin D 3 and cdk 4 , we compared the substrate specificity of the active ternary complex containing p 27 ( kip 1 ) and the active cyclin D 3 lacking p 27 ( kip 1 ) by tryptic phosphopeptide mapping of GST Rb phosphorylated in vitro and also by comparing the relative phosphorylation activity toward a panel of peptide substrates . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
INTRODUCTION : The purpose of this study was to determine whether the multiple tumor suppressor 2 ( MTS 2 ) gene , encoding an inhibitor ( p 15 ) of cyclin D dependent kinases 4 and 6 ( cdk 4 , cdk 6 ) , is deleted in head and neck squamous cell carcinomas ( HNSCC ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinases cdk 4 , cdk 2 and cdc 2 , and the associated cyclins D , E and A have been studied . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Initial studies showed that treatment of MCF 7 cells with 10 nM E 2 significantly increased cyclin D 1 ( protein and mRNA ) , cdk 2 and cdk 4 dependent kinase activities , and hyperphosphorylation of retinoblastoma ( RB ) protein . ^^^ For example , TCDD significantly inhibited E 2 induced hyperphosphorylation of RB , cyclin D 1 protein , and cdk 2 , cdk 4 , and cdk 7 dependent kinase activities . ^^^ Inhibition of E 2 induced cdk 4 dependent kinase activity by TCDD may be related to the parallel decrease of E 2 induced cyclin D 1 protein , and inhibition of induced cdk 2 and cdk 4 dependent kinase activities may be due to significantly increased p 21 levels in cells cotreated with TCDD plus E 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
However , a mutant of Cdk 4 , Cdk 4 ( N 158 ) , designed to specifically inhibit cyclin D dependent kinases through dominant negative interference , was unable to arrest the cell cycle of the same cells ( S . van den Heuvel and E . ^^^ We show that p 16 and Cdk 4 ( N 158 ) inhibit the kinase activity of cellular cyclin D 1 complexes through different mechanisms . p 16 dissociated cyclin D 1 Cdk4 complexes with the release of bound p 27 ( KIP 1 ) , while Cdk 4 ( N 158 ) formed complexes with cyclin D 1 and p 27 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Blockade of the FGF action profoundly inhibited cyclin E expression and cyclin dependent kinase 2 ( CDK 2 ) activity , but not D type cyclin expression and CDK 4 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To investigate further the observed biological effects , cyclin D 1 and cdk 4 expression and the level of phosphorylation of the retinoblastoma protein Rb were assessed . ^^^ Cyclin D 1 and cdk 4 expression and Rb phosphorylation were significantly reduced , by 40 75 % , after 24 hr of treatment with RA or 4HPR ; these decreases were either transient , e . g . , only at 24 hr for cdk 4 , or sustained for 72 hr . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
While the protein levels of cyclin D 1 , cyclin D 3 , CDK 4 , CDK 6 and CDK 2 were still detectable in adult atria , the protein levels of cyclin E , cyclin A , cyclin B , cdc 2 and PCNA were not detectable . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ectopic expression of cyclin D 2 or amplification of CDK 4 does not occur at a significant frequency in urothelial carcinomas . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The mammalian D type cyclins D 1 , D 2 , and D 3 activate the cyclin dependent kinases CDK 4 and CDK 6 in G 1 and thereby promote the cell ' s commitment to enter S phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
VEGF stimulated both cyclin D 1 synthesis and Cdk 4 kinase activity , inhibited by PD 98059 and dominant negative JNK 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of p 27 , cyclin D 1 , and the activities of Cdk 4 and Cdk activating kinase ( CAK ) , composed of Cdk 7 and cyclin H , were not affected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Thus , p 21 [ CIP 1 ] and p 27 [ KIP 1 ] , act in concert to inhibit cyclin E / CDK2 activity which , together with CDK 4 inactivation , confers a G 1 phase arrest . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Corresponding to the inhibited cdk function , we demonstrate a low expression of cyclin D in mid G 1 determined by Western blot analysis , and cyclin D was greatly reduced in the immunocomplex recovered with antibody to cdk 4 and cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
LCLs arrested in G0 / G1 by RA also showed a significant decrease in the protein levels of cyclins D 2 , D 3 and A , together with a reduction in the amount of cyclin D associated with CDK 4 and CDK 6 , probably accounting for the inhibition of the relative kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Similar to cell cycle arrest induced by serum starvation , we show here that hypoxia induced arrest is accompanied by a decrease in pRB directed CDK 4 and CDK 2 activities , lower cyclin D and E protein levels , and by an increase in p 27 protein abundance . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The increased CKI binding to CDK 2 is achieved by the redistribution of both p 21 and p 27 from CDK 4 to CDK 2 complexes subsequent to decreases in CDK 4 and cyclin D 3 expression following lovastatin treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Treatment of the CDK immune complexes with the detergent deoxycholate ( DOC ) resulted in restoration of CDK 2 , but not CDK 4 , activity at day 3 postconfluency , suggesting the presence of inhibitory protein ( s ) binding to the cyclin / CDK2 complex at this time point . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The same was found for the cyclin dependent kinases ( CDK ) CDK 2 and CDK 4 and for CDK inhibitors p21 / WAF1 , p27 / KIP1 and p16 / CDKN2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression of cyclin D 1 and cdk 4 in tumorigenesis of sporadic hepatoblastomas . ^^^ The expression of cyclin D 1 , cdk 4 , p 16 and retinoblastoma gene product ( pRb ) was studied by immunohistochemistry in 17 paraffin embedded tissues consisting of both tumor and corresponding non neoplastic tissues . ^^^ Tumor tissues showed overexpression of cyclin D 1 ( 13 / 17 , 76 % ) and cdk 4 ( 15 / 17 , 88 % ) . ^^^ Eleven cases showed co overexpression of both cyclin D 1 and cdk 4 . ^^^ These data suggest that overexpressed cyclin D 1 and cdk 4 protein might play an important role in the tumorigenesis of hepatoblastoma and that in the group with high cyclin D 1 expression , tumor recurrence may be more frequent . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression patterns of cyclin B 1 , cyclin D , cyclin E and p 53 were not different in any of the groups . mRNAs encoding CDK 1 , CDK 4 , cyclin D 1 and c myc were also increased in wild type mice fed Wy 14 , 643 but not in PPARalpha null mice . ^^^ ACO , CDK 1 , CDK 2 , CDK 4 , PCNA and c myc proteins were significantly increased in wild type mice fed Wy 14 , 643 for 5 weeks or 11 months , as compared with controls . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The tumour suppressor p 16 is a member of the INK 4 family of inhibi tors of the cyclin D dependent kinases , CDK 4 and CDK 6 , that are involved in the key growth control pathway of the eukaryotic cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
When human cDNAs encoding cyclins , cyclin dependent kinase 2 ( CDK 2 ) , CDK 4 , and cell division cycle 2 ( CDC 2 ) , were introduced , only CDK 4 overexpressing cells were more prone to apoptosis compared with parental cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Activation of cdk 4 and cdk 2 during rat liver regeneration is associated with intranuclear rearrangements of cyclin cdk complexes . ^^^ Cyclin D cdk 4 and cyclin E cdk 2 are activated during the G 1 phase , cyclin A cdk 2 is activated during the S phase , and cyclin B cdk 1 during mitosis . ^^^ In quiescent cells , cyclin D 3 and cdk 4 were cytoplasmatic , whereas cyclin D 1 was nuclear . ^^^ At 5 hours after hepatectomy , cyclin D 3 and cdk 4 began to move into the nucleus , and at 13 hours , they were mostly nuclear . ^^^ This activation was associated with the accumulation of cyclin D 1 , cyclin D 3 , and cdk 4 in a nuclear subfraction extractable with nucleases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Moreover , the overexpression of Rb or CDK 4 reduced the level of TAF ( 2 ) 250 cyclin D 1 complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overall , alterations of the G 1 pathway in neuroblastoma included relatively frequent p 16 expression and infrequent CDK 4 amplification and cyclin D 2 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ang 2 had no significant effect on the steady state levels of cyclin dependent kinase ( CDK ) inhibitor ( CDKI ) , p27kip1 , and on the activities of CDK 2 and CDK 4 , although it caused a modest increase in cyclin E levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis showed an upregulation in the protein expression of cyclin D 1 and cyclin E and their regulatory subunits cdk 4 and cdk 2 during the course of UVB exposure and in papillomas and carcinomas . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Coupling of the cell cycle and myogenesis through the cyclin D 1 dependent interaction of MyoD with cdk 4 . ^^^ Interaction between MyoD and cdk 4 disrupts MyoD DNA binding , muscle specific gene activation and myogenic conversion of 10T1 / 2 cells independently of cyclin D 1 and the CAK activation of cdk 4 . ^^^ Forced induction of cyclin D 1 in myotubes results in the cytoplasmic to nuclear translocation of cdk 4 . ^^^ The specific MyoD cdk 4 interaction in dividing myoblasts , coupled with the cyclin D 1 dependent nuclear targeting of cdk 4 , suggests a mitogen sensitive mechanism whereby cyclin D 1 can regulate MyoD function and the onset of myogenesis by controlling the cellular location of cdk 4 rather than the phosphorylation status of MyoD . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Conversely , CDK 4 stably associates with both p 21 ( CIP 1 ) and p 27 ( KIP 1 ) in cyclin containing complexes , suggesting that CDK 4 is in equilibrium between INK 4 and p 21 ( CIP 1 ) or p 27 ( KIP 1 ) bound states . ^^^ In agreement with this hypothesis , overexpression of p 21 ( CIP 1 ) in 293 cells , where CDK 4 is bound to p 16 ( INK4a ) , stimulates the formation of ternary cyclin D CDK 4 p21 ( CIP 1 ) complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Induced expression of p 16 ( INK4a ) inhibits both CDK 4 and CDK 2 associated kinase activity by reassortment of cyclin CDK inhibitor complexes . ^^^ As expected , induction of p 16 ( INK4a ) results in a G 1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein ( pRb ) by the cyclin dependent kinases CDK 4 and CDK 6 . ^^^ Sequestration of CDK 4 by p 16 ( INK4a ) allows cyclin D 1 to associate increasingly with CDK 2 , without affecting its interactions with the CIP / KIP inhibitors . ^^^ Thus , upon the induction of p 16 ( INK4a ) , p 27 ( KIP 1 ) appears to switch its allegiance from CDK 4 to CDK 2 , and the accompanying reassortment of components leads to the inhibition of cyclin E CDK 2 by p 27 ( KIP 1 ) and p 21 ( CIP 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Progesterone inhibits estrogen induced cyclin D 1 and cdk 4 nuclear translocation , cyclin E and cyclin A cdk 2 kinase activation , and cell proliferation in uterine epithelial cells in mice . ^^^ Using a simple method to isolate the uterine epithelium with high purity , we have shown that E 2 treatment induces a relocalization of cyclin D 1 and , to a lesser extent , cdk 4 from the cytoplasm into the nucleus and results in the orderly activation of cyclin E and cyclin A cdk 2 kinases and hyperphosphorylation of pRb and p 107 . ^^^ P 4 pretreatment did not alter overall levels of cyclin D 1 , cdk 4 , or cdk 6 nor their associated kinase activities but instead inhibited the E 2 induced nuclear localization of cyclin D 1 to below the control level and , to a lesser extent , nuclear cdk 4 levels , with a consequent inhibition of pRb and p 107 phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Our results show that IL 6 treatment of early stage melanoma cell lines caused G 1 arrest , which could not be explained by changes in levels of G 1 cyclins ( D 1 , E ) , cdks ( cdk 4 , cdk 2 ) or by loss of cyclin / cdk complex formation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , cyclin B , cdk 4 , and cdc 2 protein expression and kinase activities remain constant . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
L 34 also interacts with Cdk 4 and , in parallel , inhibits the Cdk4 / cyclin D 1 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RESULTS : The newly expressed p 16 formed a complex with cdk 4 , and phosphorylated pRB was decreased , although cyclin D 1 and pRB : cyclin D 1 complex were unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The kinase activities of two G1 / S cyclin dependent kinases , CDK 2 and CDK 4 , are inhibited in Calu 1 cells treated with GGTI 298 . ^^^ Furthermore , GGTI 298 has little effect on the expression levels of CDK 2 , CDK 4 , CDK 6 , cyclins D 1 and E , but decreases the levels of cyclin A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The widely prevailing view that the cyclin dependent kinase inhibitors ( CKIs ) are solely negative regulators of cyclin dependent kinases ( CDKs ) is challenged here by observations that normal up regulation of cyclin D CDK 4 in mitogen stimulated fibroblasts depends redundantly upon p 21 ( Cip 1 ) and p 27 ( Kip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
ET 1 increased cyclin D 1 protein ( 5 . 1+ / 1 . 9 fold increase , 8 hours after stimulation , P < 0 . 05 ) , cdk 4 kinase activity ( 2 . 8+ / 0 . 5 fold increase , 12 hours after stimulation , P < 0 . 01 ) , and cdk 2 kinase activity ( 2 . 1+ / 0 . 4 fold increase , 16 hours after stimulation , P < 0 . 05 ) in a time and dose dependent manner . ^^^ ET 1 induced increase in cyclin D 1 protein , and cdk 4 kinase activity was not significantly inhibited by an inhibitor of the mitogen activated protein kinase kinase 1 / 2 , PD 98059 , nor by the protein kinase C inhibitor calphostin C , whereas ET 1 induced upregulation of cyclin D 1 protein and cdk 4 kinase activity was significantly inhibited by the phosphatidylinositol 3 kinase inhibitor LY 294002 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RESULTS : The protein expression of cyclin ( D 1 , D 3 , E , and A ) and CDKs ( CDK 4 , CDK 2 , and cdc 2 ) was higher in primary colorectal carcinoma tissue than in adjacent normal tissue . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The protein also interacts with Cdk 4 and inhibits the Cdk4 / cyclin D 1 enzyme . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The amount of cyclin D and of the related CDK 4 , governing the G 1 phase of the cell cycle , increased during megakaryocyte development , maintaining high levels of expression also in mature megakaryocytes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , induction of the cell cycle regulators cyclin D 2 and cdk 4 are secondary events , which require de novo protein synthesis . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In these clones , binding of p 16 to cdk 4 and cdk 6 abrogated binding of cyclin D 1 , p 27 ( KIP 1 ) , and p 21 ( WAF1 / CIP1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blots showed that the expression of cell cycle dependent kinases ( cdk 2 and cdk 4 ) , cyclin D 1 and p 53 was significantly reduced , while WAF 1 was increased , after BFA treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A cyclin D Cdk 4 activity required for G 2 phase cell cycle progression is inhibited in ultraviolet radiation induced G 2 phase delay . ^^^ Cyclin D Cdk 4 complexes have a demonstrated role in G 1 phase , regulating the function of the retinoblastoma susceptibility gene product ( Rb ) . ^^^ Here we report that in UV irradiated HeLa and A 2058 cells , p 16 bound Cdk 4 and Cdk 6 complexes with increased avidity and inhibited a cyclin D 3 Cdk4 complex normally activated in late S / early G 2 phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This increase correlated with the elevated expression of various cyclin dependent kinase subunits , such as cyclin A , and to a lesser extent , cyclin D , cdk 2 , and cdk 4 . ^^^ Thus , the remarkably low proliferative activity of normal human corneal endothelial cells appears to be regulated at two levels : the expression of certain cell cycle regulatory proteins that are essential for cell cycle progression is extremely low ( cyclin A ) or somewhat low ( cdk 2 and cdk 4 ) ; but the amount of p 21 and p 27 , inhibitors of cell cycle progression , is very high . ^^^ However , the growth inhibitory status of these components is clearly reversible : upon transduction with large T antigen , the expression of cyclin A , cyclin D , cdk 2 , and cdk 4 is induced , whereas the expression of p 21 and p 27 is inhibited , and the cells proliferate . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Aberrant expression of the cell cycle associated proteins TP 53 , MDM 2 , p 21 , p 27 , cdk 4 , cyclin D 1 , RB , and EGFR in cervical carcinomas . ^^^ OBJECTIVE : The aims of this study were to study aberrant expression and coexpression of the cell cycle associated proteins TP 53 , p 21 , p 27 , cyclin D 1 , cdk 4 , RB , EGFR , and MDM 2 in cervical carcinomas , to correlate protein alterations with histopathological and clinical parameters , and to evaluate whether these alterations provide prognostic information . ^^^ RESULTS : In normal cervical epithelium p 27 immunostaining was identified in more than 50 % of the cells , cdk 4 in 5 50 % of the cells , and EGFR in less than 5 % of the cells , whereas no immunostaining for TP 53 , p 21 , MDM 2 , or cyclin D 1 was detected . ^^^ Overexpression of p 21 was found in 96 % of the tumors , MDM 2 in 35 % , cdk 4 in 69 % , cyclin D 1 in 3 % , and EGFR in 20 % of the tumors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this study we characterized a human osteosarcoma cell line , MG 63 , for the expression level of cyclin D 1 , cyclin E , cdk 4 , cdk 2 , and cell cycle inhibitors pRb and p 21 . ^^^ TNF alpha did not affect the amount of cyclin D 1 , cyclin E , cdk 4 , cdk 2 , and of cyclin D 1 cdk4 complex . ^^^ Cyclin D 1 and cdk 4 expression and their complex did not change after IL 6 treatment , nor did cyclin E and cdk 2 protein expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cdk 4 and p 27 were expressed in a similar subset of testicular and ovarian cells , suggesting that they may regulate cyclin D 3 function during testicular and ovarian development in a cell type specific manner . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
CDK 4 kinase activities were unaffected , as were the levels of the CDK inhibitor p21Cip1 present in cyclin E immunocomplexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cells arrested in G 1 by ectopically expressed p19ARF contained considerably reduced G 1 cyclin dependent kinase ( cdk 2 and cdk 4 ) activities . ^^^ The expression of cyclin A ( a regulatory subunit of cdk 2 ) markedly decreased , while cyclin D 1 , the major cdk 4 partner in fibroblasts , expressed at a slightly higher level and formed complexes with cdk 2 and cdk 6 in addition to cdk 4 . ^^^ Induction of p19ARF activated p 53 by increasing its stability , and allowed the expression of p21Cip1 , which bound to all of the cyclin D 1 cdk complexes ( cyclin D 1 cdk2 , cdk 4 , and cdk 6 ) thereby inhibiting their kinase activities . p19ARF formed complexes with several cellular proteins including mouse MDM 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression levels of cdk 2 , cdk 4 and cdk 6 were the same in 3T3 PCNA and NIH 3T3 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Myc regulates cyclin D Cdk 4 and Cdk 6 activity but affects cell cycle progression at multiple independent points . c myc is a cellular proto oncogene associated with a variety of human cancers and is strongly implicated in the control of cellular proliferation , programmed cell death , and differentiation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Silibinin induced G 1 arrest was associated with a marked decrease in the kinase activity of cyclin dependent kinases ( CDKs ) and associated cyclins because of a highly significant decrease in cyclin D 1 , CDK 4 , and CDK 6 levels and an induction of Cip1 / p21 and Kip1 / p27 followed by their increased binding with CDK 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In mammals , cyclin D can assemble with CDK 4 and CDK 6 , but not with Cdc 2 , to form active complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here we show that during early phase G 1 arrest which occurs in UV irradiated human U 343 glioblastoma cells , there are ( 1 ) decreases in cyclin D 1 and cdk 4 levels which parallel a loss of S phase promoting cyclin D1 / cdk4 complexes , and ( 2 ) increases in p 53 and p 21 protein levels . ^^^ We also show that the late phase UV induced apoptosis of U 343 cells occurs after cell cycle re entry and parallels the reappearance of cyclin D 1 and cdk 4 and cyclin D1 / cdk4 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Under these conditions , CDK 2 and CDK 4 protein expression remained unchanged compared with proliferating cells , but expression of cyclin D 1 and p 27 ( KIP 1 ) was down regulated and cyclin E accumulated in the inactive form . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclins B and E , and protein kinase CDK 2 and CDK 4 expressions were not affected by HNE , whereas DMSO induced an increase of cyclin E , B , and CDK 2 from 8 h to 1 day . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression of cyclin D 1 and / or cdk 4 , and loss of expression of p 16 ( the natural inhibitor of cyclin D 1 cdk4 activity ) , have been implicated in several cancers . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The D type cyclins ( cyclin D 1 , D 2 , and D 3 ) promote cell cycle progression from G 1 to S phase by binding to and activating the cyclin dependent kinases Cdk 4 and Cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To this end , immunohistochemistry and immunoblotting for PCNA , Cdk 4 , cyclin D , cyclin A , and the Cdk inhibitor p27 / kip1 , as well as in situ end labeling for apoptotic DNA fragmentation , were applied to cerebella of P 7 P21+ / + , wv / + , and wv / wv mice . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , cyclin D1 / cyclin dependent kinase ( CDK ) complex formation increased in the transgenic mice and was correlated with elevated CDK 4 and CDK 6 kinase activities . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The results demonstrate that TGF beta 1 mediated conversion of hyperplasia to hypertrophy involves preventing activation of cdk2 / cyclin E kinase but has no effect on cdk 4 ( 6 ) / cyclin D kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Accumulation of these cells at G 1 is not associated with major changes in expression level of cyclin dependent kinase ( cdk ) 2 , cdk 4 , and cdk 6 ; cyclin D 1 and cyclin E ; or p 16 , p 21 , p 27 , and p 57 after CPT treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this study , we examined the mechanism by which t RA blocks cell cycle progression in HBE cells and the possibility that this signaling event is blocked in non small cell lung cancer ( NSCLC ) cells that are refractory to the growth inhibitory effects of t RA . t RA suppressed the expression and activity of cyclin D 1 , cyclin E , and cyclin dependent kinases ( CDK ) 2 and CDK 4 , increased expression of the CDK inhibitor p 27 , and shifted the retinoblastoma protein to a hypophosphorylated form . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In proliferating cells , endogenous cdk 4 is distributed among three populations : an abundant high molecular mass ( > 400 kDa ) pool of latent cdk 4 that serves as a source of cdk 4 for cyclin D , a low abundance pool containing active cyclin D cdk 4 complexes , and an inactive population of monomeric cdk 4 . ^^^ This process of TGF beta induced cdk 4 inactivation is completely blocked by expression of c Myc , even though the latent and active cdk 4 complexes from c Myc expressing cells remain sensitive to dissociation by p 15 in vitro . c Myc causes a small increase in cyclin D levels , but this effect contributes little to the loss of TGF beta responses in these cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The current study is concerned with the evaluation of a key cyclin ( cyclin D 1 ) which activates cdk 4 and p27KIP1 which in turn inhibit cdk 2 in the proliferative responses of epidermal growth factor ( EGF ) and platelet derived growth factor ( PDGF ) and their modulation by TGF beta 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunocomplex kinase experiments showed that EGCG inhibited the activities of cyclin dependent kinase 2 ( Cdk 2 ) and 4 ( Cdk 4 ) in a dose dependent manner in the cell free system . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In order to study this cell cycle regulatory mechanism in murine T cell lymphomas , we have analyzed the RNA and protein expression of the cyclin D 1 , cdk 4 and retinoblastoma genes in primary tumor samples . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunohistochemical analysis of the D type cyclin dependent kinases Cdk 4 and Cdk 6 , using a series of monoclonal antibodies . ^^^ Cellular signal transduction cascades triggered by mitogenic or antiproliferative cues eventually converge on a biochemical mechanism centered around the retinoblastoma tumor suppressor ( pRb ) , the so called RB pathway that governs G 1 phase progression and guards the commitment to enter S phase . pRb , together with its immediate upstream regulators , the D type cyclins , their partner cyclin dependent kinases Cdk 4 and Cdk 6 , and the Cdk inhibitors , form a functional unit that is involved in major decisions about cellular fate , and whose components , including the proto oncogenic cyclin D dependent kinases , are commonly deregulated in many types of cancer . ^^^ Collectively , the antibodies described in this study provide the means for immunochemical analyses of the cyclin D dependent kinases in human and animal cells , and represent useful molecular tools that should help better understand the biological roles of Cdk 4 and Cdk 6 in normal cell cycle control , and their oncogenic activity in tumor cells . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cdk 4 and Cdk 6 immune complexes recovered from B cells following BCR Fc gamma R co cross linking are devoid of coprecipitated D type cyclins , indicating that inhibition of their Rb protein kinase activities is due in part to the absence of bound D type cyclin . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Gsp gene , that may play an important role in 40 % of GH producing tumor , activation of 10 % of non functioning tumors and 6 % of corticotroph adenomas , produces cAMP , which stimulates cyclin D 1 and D 3 which later produce cdk 2 and cdk 4 respectively , and stimulates cell progression from G 1 to S phase . cAMP also induces ras gene , which inhibits binding of pRb with E2F that is necessary to prevent action of E2F in accelerating cell cycle . ^^^ MEN 1 gene , although found in some sporadic tumors , is more likely associated with familial adenoma . p 53 , Ras , Rb , nm 23 and c myc genes play some role in the promotion of tumors especially toward their aggressive variant . p 53 gene , which is found in up to 60 % of ACTH producing adenomas , through action of p 21 inhibits progression of cell cycle from G 1 to S phase , by inhibiting the action of cyclin D 3 on cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression of cyclin D 1 , Cdk 4 , and E2F1 in the cells expressing pRb and p 21 did not perturb the interaction between p 21 and pRb . ^^^ Coexpression of p 21 in cells expressing pRb , cyclin D 1 , and Cdk 4 prevented pRb hyperphosphorylation by cyclin D1 / Cdk4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Thus , the decline in cdk 4 activity and the induction of retinoblastoma hypophosphorylation follows cyclin D 1 decline . ^^^ Turnover studies demonstrate that the half life of cyclin D 1 ( approximately 30 min ) is not shortened in flavopiridol exposed cells , and that the turnover of cdk 4 bound cyclin D 1 is unaltered . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
An increased expression of cyclin D 1 and cyclin dependent kinase 5 ( cdk 5 ) was observed from day 9 after transplantation , whereas only slight alteration of cdk 4 expression was found . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Disruption of these pathways can occur through inactivation of p 16 or p 53 , or activating mutations of cyclin dependant kinase 4 gene ( Cdk 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
There was no effect on p 21 ( Cip 1 ) , cyclin D 2 , cdk 4 , and cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In many organisms , initiation and progression through the G ( 1 ) phase of the cell cycle requires the activity of G ( 1 ) specific cyclins ( cyclin D and cyclin E ) and their associated cyclin dependent kinases ( CDK 2 , CDK 4 , CDK 6 ) . ^^^ We show here that the Caenorhabditis elegans genes cyd 1 and cdk 4 , encoding proteins similar to cyclin D and its cognate cyclin dependent kinases , respectively , are necessary for proper division of postembryonic blast cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
It is unlikely that the lack of inhibitory function of p21Cip1 / Waf1 can be explained by its inability to bind Cdk 2 and Cdk 4 kinases or PCNA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p 53 , p 21 ( WAF / CIP1 ) , Rb , p 16 ( INK4A ) , CDK 4 and Cyclin D 1 , MIB 1 ( Ki 67 ) and BCL 2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx ( n = 26 ) , hypopharynx ( n = 10 ) and larynx ( n = 7 ) by applying immunohistochemistry to paraffin sections of tumor specimens . ^^^ CONCLUSION : The results of this pilot study indicate that CDK 4 and cyclin D 1 over expression provide useful prognostic information about clinical outcome after primary radiochemotherapy of head and neck cancer patients . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Nevertheless , cyclin D 3 and CDK 4 activity are essential in the cAMP dependent mitogenesis , and cAMP unmasks the DCS 22 epitope of cyclin D 3 and induces the nuclear translocations and assembly of cyclin D 3 and CDK 4 in a complex that also contains p 27 ( kip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The decrease in pRB phosphorylation correlated with inhibitor induced suppression of G ( 1 ) cyclin dependent kinases including CDK 2 , CDK 4 , and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the present experiment , we investigated expression of cell cycle related proteins , i . e . , cyclin B 1 , cyclin D 1 , cdk 4 , and PCNA , in rat brain after transient MCA occlusion , and compared the temporal profile of the results with that of TUNEL study , which detects double strand breaks in DNA . ^^^ These results indicate that aberrant expression of cdk 4 , but not cyclin B 1 , cyclin D 1 or PCNA , actually takes place in the brain after MCA occlusion , but this is not the causative mechanism of apoptotic cell death in the brain with ischemia . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of cell cycle regulatory proteins demonstrated that As ( 2 ) O ( 3 ) ( 2 microM ) did not change the steady state levels of CDK 2 , CDK 4 , CDK 6 , cyclin D 1 , cyclin E and cyclin A , but decreased the protein levels of cdc 2 and cyclin B 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
More important , we find that overexpression of cyclin D 2 is accompanied by acquisition of new partners such as cyclin dependent kinase 2 ( cdk 2 ) , cdk 4 , and cdk 6 in infected cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TPX activated p 21 ( waf 1 ) transcription that led to elevated p 21 ( waf 1 ) protein levels in three human tumor cell lines without altering the protein levels of cdk 2 , cdk 4 , or cyclin B . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The p 16 ( INK4a ) tumor suppressor inhibits cyclin dependent kinases ( CDK 4 and CDK 6 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Complex mechanisms underlying impaired activation of Cdk 4 and Cdk 2 in replicative senescence : roles of p 16 , p 21 , and cyclin D 1 . ^^^ Cdk 4 derived from early passage quiescent cells was effectively activated by incubation with cyclin D 1 and Cdk activating kinase ( CAK ) in vitro , whereas Cdk 4 from senescent cells was not . ^^^ Thus , one of the underlying molecular events involved in replicative senescence is the impaired activation of Cdk 4 and Cdk 2 due to increased binding of p 16 to Cdk 4 and increased association of Cdk 2 with cyclin D 1 and p21 . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
ODC overexpression did not affect cyclin D / cyclin dependent kinase 4 ( Cdk 4 ) dependent phosphorylation of retinoblastoma protein but stimulated cyclin E / Cdk2 and cyclin A / Cdk2 associated kinase activity , with minimal effect on the levels of these proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The INK 4 family of cyclin dependent kinase ( CDK ) inhibitors includes four 15 to 19 kDa polypeptides ( p 16 ( INK4a ) , p 15 ( INK4b ) , p 18 ( INK4c ) , and p 19 ( INK4d ) ) that bind to CDK 4 and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have constructed a novel fusion gene consisting of full length human cyclin D 1 and cdk 4 genes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We investigated the immunoreactivity of p 27 , p 21 , cdk 4 , cyclin D 1 and p 53 in 77 node negative breast carcinomas , with long term follow up ( mean 163 months ; range 20 227 ) . ^^^ Nuclear staining for p 27 was seen in 87 % of the carcinomas , for cdk 4 in 92 % , for p 21 in 68 % , for cyclin D 1 in 58 % and for p 53 in 18 % . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
After 70 % partial hepatectomy in rats , there was upregulation of kinase activity associated with cyclins ( A , D 1 , D 3 , and E ) , cyclin dependent kinases ( Cdk 2 and Cdk 4 ) , and Cdk inhibitory proteins ( p 27 , p 107 , and p 130 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The induction of cyclin A and cdc 2 , the phosphorylation of cdk 2 , the nuclear translocation of cdk 4 and the assembly of cyclin D 3 cdk4 complexes required the synergy of TSH and insulin . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cell cycle proteins ( cyclin D 1 and cdk 4 ) after controlled cortical impact in rat brain . ^^^ We measured the expression of Cyclin D 1 and its kinase cdk 4 , 48 h after induction of cortical contusion in the rat . ^^^ Double staining for DNA fragmentation detection , using terminal deoxynucleotdyl transferase mediated biotinylated deoxyuridine triphosphate nick end 3 ' OH labeling ( TUNEL ) and antibodies for expression of Cyclin D 1 and cdk 4 was also performed . ^^^ Cyclin D 1 and cdk 4 were selectively expressed in morphologically intact or injured neurons throughout the rat brain . ^^^ Apoptotic cells were not immunoreactive to Cyclin D 1 and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although several factors have been implicated in the regulation of Cdk 4 activity , little is known regarding the contributions of cyclin dependent kinase inhibitors ( CKIs ) in Cdk 4 activation in the mid G 1 phase . ^^^ Following CSF 1 stimulation , Cdk 4 bound to cyclin D 1 and then to p 21 , concomitant with the dissociation of p 15 from the complexes . ^^^ During regeneration of mouse liver after partial hepatectomy , Cdk 4 activity coincided precisely with ternary complex formation of cyclin D1 / Cdk4 / p21 . ^^^ Using the baculovirus expression system , we succeeded in reconstituting a capacity for Cdk 4 activation in insect cells , forming an active cyclin D1 / Cdk4 / p21 ternary complex . ^^^ Taken together , it is suggested that p 21 and cyclin D 1 act cooperatively as activators of Cdk 4 through the release of CKIs of the INK 4 family . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To further investigate the differences between mitogen induced mouse hepatocyte proliferation and liver regeneration after PH , we have measured the expression of cyclin D 1 , cyclin D 3 , cyclin E , and cyclin A and of the cyclin dependent kinases CDK 2 , CDK 4 , and CDK 6 . ^^^ The expression of other proteins involved in cell cycle control , such as cyclin dependent kinases ( CDK 4 , CDK 2 , CDK 6 ) , was also analyzed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 and Cdk 4 protein induction in motor neurons after transient spinal cord ischemia in rabbits . ^^^ In situ terminal deoxynucleotidyl transferase ( TdT ) mediated dUTP biotin nick end labeling ( TUNEL ) , DNA fragment with gel electrophoresis , Western blot analysis for cyclin D 1 and Cdk 4 , and temporal profiles of cyclin D 1 and Cdk 4 immunoreactivity were investigated . ^^^ Immunoreactivity of cyclin D 1 and Cdk 4 proteins was induced selectively at 8 hours in motor neuron nuclei , which eventually died . ^^^ CONCLUSIONS : These results indicate that induction of cyclin D 1 and Cdk 4 may be implicated in programmed cell death change after transient spinal cord ischemia in rabbits . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Abnormal expression of p 16 or pRb was defined by negative nuclei staining , and that of CDK 4 and cyclin D 1 was defined by 50 % nuclear staining . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We investigated 3 normal adrenals , 31 adrenocortical tumors [ 11 tumors with normal expression of the IGF 2 gene ( mainly benign ) and 20 with IGF 2 gene overexpression ( mainly malignant ) ] , and the human adrenocortical tumor cell line NCI H295R for expression of the p57KIP2 gene , G 1 cyclins ( cyclin D 2 and E ) and G 1 CDK ( CDK 2 , CDK 3 and CDK 4 ) protein contents and for kinase activity of G 1 cyclin CDK complexes . ^^^ By contrast , abrogation of the p57KIP2 gene expression and increased expression of G 1 cyclins ( cyclin E ) and G 1 CDKs ( CDK 2 and CDK 4 ) were associated with high activity of G 1 cyclin CDK complexes in malignant tumors and in the H295R cell line . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Both p 16 and p 15 , encoded by genes located on chromosome 9p21 , are inhibitors of cyclin dependent kinases 4 / 6 ( CDK4 / 6 ) and upstream regulators of RB function , and set up the RB / p16 tumor suppressive pathway , which is abrogated frequently in human neoplasms , either through inactivation of the RB or p 16 tumor suppressor protein , or alteration of the cyclin D 1 or CDK 4 oncoproteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of G ( 1 ) regulatory proteins demonstrated that protein levels of CDK 2 , CDK 4 , cyclin D 1 , and cyclin A were decreased in a time dependent manner , but not those of CDK 6 and cyclin E , by EB 1089 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These differences correlated with the growth fraction for both the G 1 cyclins cdks ( r = 0 . 91 , 0 . 94 , 0 . 85 , 0 . 90 and 0 . 96 for cyclin D 1 , cyclin E , cdk 2 , cdk 4 and cdk 6 , respectively ) and the G2M cyclins cdks ( r = 0 . 96 , 0 . 97 and 0 . 93 for cyclins A , B and cdkl respectively ) . ^^^ Overexpression of other cyclins cdks were observed , from the 6th day on for cyclin D 1 , the 12th day for cdk 2 and cdk 4 , the 15th day for cdk 6 and the 20th day for cyclin E . ^^^ These increases persisted during tumoral progression and correlated with the growth fraction ( r = 0 . 85 , 0 . 94 , 0 . 93 , 0 . 96 , and 0 . 98 for cyclin D 1 , cyclin E , cdk 2 , cdk 4 and cdk 6 , respectively ) ( n = 20 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of G 1 regulatory proteins demonstrated that the protein levels of cyclin dependent kinase ( CDK ) 2 , CDK 4 , CDK 6 and cyclin E were decreased after treatment with lovastatin ( 10 microM ) in a time dependent manner , but not cyclin D 1 . ^^^ In addition , lovastatin increased the protein level of the cyclin dependent kinase inhibitor ( CDKI ) , p 27 , and markedly enhanced the binding of p 27 with CDK 2 and CDK 4 more than CDK 6 after 24 h exposure . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We found that VK 3 inhibited cyclin E expression at late G 1 phase and cyclin A at G1 / S transition of the aphidicolin synchronised SiHa cells , but had no effect on Cdk 2 and Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Moreover , ectopic expression of cyclin D 1 and Cdk 4 can stimulate the Brca 1 promoter in an E2F dependent manner , and this is inhibited by coexpression of the p 16 ( INK4a ) cyclin dependent kinase inhibitor . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , HSV infection prevented the normal G 1 increases in cyclin D 1 and D 3 protein levels , and blocked the normal G 1 appearance of new electrophoretic forms of cdk 2 and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The inhibition of cyclin D / CDK4 , 6 kinase activity corresponded to a loss of cyclin D 1 protein and a failure of CDK 4 and CDK 6 to translocate to the nucleus . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Loss of p16INK4a expression would disrupt the retinoblastoma ( Rb ) / p16INK4a / cyclin D dependent kinase ( CDK 4 ) pathway , whereas loss of p14ARF expression would inactivate both the Rb and p53 / MDM2 / p14ARF pathways through MDM 2 , which can complex with either Rb or p 53 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
During IL 6 induced macrophage differentiation of M 1 cells , IL 6 down regulated cyclin D 1 expression and induced p 19 ( INK4D ) expression , leading to reduction in cdk 4 activities . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We investigated overexpression of cyclin D 1 ( CCND 1 ) , cyclin D 2 ( CCND 2 ) , cyclin E ( CCNE ) , CDK 2 , and CDK 4 , in addition to p 27 , in 260 gastric cancer cases on the basis of Western blots , reverse transcriptase polymerase chain reaction Southern blots , and immunohistochemistry to clarify the roles of these proteins in tumor progression and prognosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , ( 1 ) the arrest of G ( 1 ) S transition exerted by PC 3 was completely rescued by coexpression of cyclin D 1 but not by that of cyclin A or E ; ( 2 ) expression of PC 3 caused a significant down regulation of cyclin D 1 protein levels , also in Rb defective cells , accompanied by inhibition of CDK 4 activity in vivo ; and ( 3 ) the removal from the PC 3 molecule of residues 50 to 68 , a conserved domain of the PC3 / BTG / Tob gene family , which we term GR , led to a loss of the inhibition of proliferation as well as of the down regulation of cyclin D 1 levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The concentrations of most cyclin dependent kinases ( Cdk 2 , Cdk 4 , and Cdk 6 ) , however , were unchanged by PMA treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although cyclin D 1 accumulated on normal schedule , cdk 4 , which increased following restimulation in amino acid replete medium , was not induced when arginine was absent . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Loss of phosphorylation of the retinoblastoma protein was noted and cdk 4 and cyclin E / cdk 2 activities fell . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As already reported , oncogenic Ras expression was sufficient to induce cyclin D 1 and p21cip1 expression and their association with cdk 4 . ^^^ Furthermore , serum starved [ Lys 61 ] N Ras NIH3T3 cells showed nuclear accumulation of cyclin D 1 and cdk 4 not observed in serum starved NIH3T3 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Inhibition of CDK 2 , CDK 4 and cyclin E and increased expression of p27Kip1 during treatment with interferon alpha in carcinoid tumor cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Nevertheless , TSH induces the nuclear translocations and assembly of cyclin D 3 and cdk 4 , which are essential in cAMP dependent mitogenesis . ^^^ In TSH stimulated cells , TGFbeta did not affect the expression of cyclin D 3 , cdk 4 , and p 27 ( kip 1 ) , nor the induced formation of cyclin D 3 cdk4 complexes , but it prevented the TSH induced relocalization of p 27 ( kip 1 ) from cdk 2 to cyclin D 3 cdk4 . ^^^ It prevented the nuclear translocations of cdk 4 and cyclin D 3 without altering the assembly of cyclin D 3 cdk4 complexes probably formed in the cytoplasm , where they were prevented from sequestering nuclear p 27 ( kip 1 ) away from cdk 2 . ^^^ It provides a new mechanism of regulation of proliferation by TGFbeta , which points out the subcellular location of cyclin D cdk 4 complexes as a crucial factor integrating mitogenic and antimitogenic regulations in an epithelial cell in primary culture . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D cyclin cdk activity is required for Rb phosphorylation in 5 Jun transformed cells , since ectopic expression of the cdk 4 and cdk 6 specific inhibitor p 16 ( INK4A ) inhibits both DNA synthesis and cell proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , cyclin D Cdk 4 was not inhibited by His ( 6 ) p 27 in vitro or p 27 ( Kip 1 ) in vivo . ^^^ These results suggest a concerted model of progestin action whereby p 27 ( Kip 1 ) and p 18 ( INK4c ) cooperate to inhibit cyclin E Cdk 2 and Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Using an in vitro competition / association assay , we demonstrate that cyclin D 1 alone , Cdk 4 alone and / or cyclin D1 / Cdk4 complexes do not compete for the p57Kip2 homodimers formation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The molecular events that lead to melanoma cell autonomous growth are not well defined , but are likely to include sustained activity of cyclin dependent kinases ( CDK 2 , CDK 4 and CDK 6 ) as a result of loss of CDK inhibitors ( such as p16INK4a and possibly p27KIP1 ) , and persistent upregulation of several cyclins ( cyclin D 1 , cyclin A and cyclin E ) , the positive regulators of CDKs . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Prostaglandin F ( 2alpha ) ( PGF ( 2alpha ) ) , a mitogen for Swiss 3T3 cells , triggers cyclin D 1 mRNA / protein expression prior to cellular entry into the S phase , but fails to raise cdk 4 or cyclin D 3 levels , while 1 oleoyl 2 diacylglycerol ( OAG ) , a protein kinase C ( PKC ) and tyrosine kinase ( TK ) activator , induces only cyclin D 1 expression with no mitogenic response . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This effect was associated with reduction of cyclin D 1 , cdk 4 and CDK activating kinase ( cyclin H and cdk 7 ) protein in HSC 3 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A tumor suppressor gene , p 16 ( INK 4 ) , which is deleted or mutated in tumors , regulates cell cycle progression through a G ( 1 ) S restriction point by inhibiting CDK 4 ( CDK 6 ) / cyclin D mediated phosphorylation of pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cdk 4 activity of the control and cyclin D 1 transfectants in colonization assays was comparable , but the cdk 2 activity was higher in the latter . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this study we provide biochemical evidence showing that delayed progression through the G 1 phase occurs concomitantly with : an increase in both nuclear bound and total p21waf1 / cip1 protein levels ; an increase in the amount of p21waf1 / cip1 associated with cdk 4 ; the inhibition of cyclin D 1 associated cdk 4 kinase activity ; and a reduction in the levels of hyperphosphorylated forms of retinoblastoma protein , and particularly , in phosphorylated Ser 780 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D 1 , p16INK4a and pRb expression in resectable non small cell lung cancer . p 21 ( p21WAF1 / CIP1 ) is involved in cell cycle regulation , as an inhibitor of cyclin dependent kinases ( CDK 2 , CDK 4 and CDK 6 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Previous studies have demonstrated that cyclin D 1 ubiquitination is dependent on its phosphorylation by glycogen synthase kinase 3beta ( GSK 3beta ) on threonine 286 and that this phosphorylation event is greatly enhanced by binding to CDK 4 ( Diehl , J . ^^^ We show that , when unbound to CDK 4 , a cyclin D 1 T286A mutant is ubiquitinated . ^^^ Further , we show that a mutant of cyclin D 1 that can not bind to CDK 4 ( cyclin D 1 KE ) is also ubiquitinated in vivo . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To investigate whether alteration of other components in pRb pathway is an alternative mechanism underlying the development of these chemically induced lymphomas , we have examined the genetic status of Rb 1 , Ccnd 1 and Cdk 4 genes that encode retinoblastoma protein , cyclin D 1 and cyclin dependence kinase 4 , respectively . ^^^ These results indicate that the mechanisms underlying the development of 2 ' , 3 ' dideoxycytidine and 1 , 3 butadiene induced lymphomas involve inactivation of p16 / p15 cyclin dependent kinase inhibitors but not genomic alterations of the Rb 1 , Ccnd 1 and Cdk 4 genes . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ectopic expression of PSM RB in SAOS 2 cells resulted in a decrease in both Cyclin A and Cdk 2 protein levels without affecting Cyclin E or Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Levels and interactions of p 27 , cyclin D 3 , and CDK 4 during the formation and maintenance of the corpus luteum in mice . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In conclusion , losses of p 16 and p 27 seem to play a significant role during the gastric carcinogenesis , and the G 1 checkpoint cell cycle proteins such as pRb , cdk 4 , cyclin D 1 , and cyclin E variably participate in the gastric carcinogenesis and metastasis by the mechanisms which are yet unknown ; thus , further studies need to be performed to elucidate the mechanisms . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
E6 / E7 expression in mouse epidermis is correlated with increased levels of the p 53 , p 21 , p 27 , cdk 2 , cdk 4 , cdk 6 , cyclin D 1 and cyclin E regulatory proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the present study , we analysed 34 de novo diffuse large B cell lymphoma ( DLCL ) from a population based lymphoma registry for alterations of the RB 1 pathway at the genetic ( RB 1 and CDK 4 ) and protein ( pRb , cyclin D 1 , cyclin D 3 , CDK 4 , and E2F 1 ) level . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To this purpose , we related the proliferative factors proliferating cell nuclear antigen ( PCNA ) , cyclin A , cyclin D 1 , cyclin dependent kinase 2 ( cdk 2 ) , cdk 4 and the proportion of cell cycle phases in NSCLC to the survival times of 150 patients . ^^^ Corresponding results were obtained with the factor cyclin A ( 64 vs 92 weeks ) , with the factor cdk 2 ( 76 vs 89 weeks ) , with the factor cdk 4 ( 62 vs 102 weeks ) and with the proportion of S phases ( 86 vs 121 weeks ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Unusual regulation of cyclin D 1 and cyclin dependent kinases cdk 2 and cdk 4 during in vivo mitotic stimulation of olfactory neuron progenitors in adult mouse . ^^^ Cyclin D 1 , cyclin E , and cyclin dependent kinase cdk 2 levels , low in olfactory organ of intact mice , increased 3 days after bulbectomy in parallel with PCNA levels ; cdk 4 content was initially high and unaffected by lesioning . ^^^ Immunoprecipitation of cdk 2 and cdk 4 fractions of protein extracts at 4 days postlesion ( mitotic reaction peak ) versus control , followed by cyclin D 1 immunoblotting , and vice versa , revealed that levels of both cyclin D1 / cdk2 and cyclin D1 / cdk4 complexes , as well as their kinase activities , were dramatically increased after lesion . ^^^ In vivo proliferation of olfactory neuronal lineage cells thus involves functional binding of cyclin D 1 with cdk 2 and cdk 4 , with differential activation mechanisms for cdk 2 and cdk 4 . ^^^ Cyclin D 1 , cyclin E , and cyclin dependent kinase cdk 2 levels , low in olfactory organ of intact mice , increased 3 days after bulbectomy in parallel with PCNA levels ; cdk 4 content was initially high and unaffected by lesioning . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The time course study revealed that expression of cyclin D ( 1 ) , cdk 2 , and cdk 4 was significantly ( > 50 % ) downregulated in 3 h of MG ( 3 mM ) exposure , followed by the dephosphorylation of retinoblastoma protein by 6 h . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To better understand these mechanisms in long term cultured lymphocytes we have characterized two human long term cultured IL 2 dependent T cell lines regarding telomere length , telomerase activity , and the expression of selected cell cycle regulators ( pRb , p 53 , cyclin E , cyclin D 1 , cyclin D 2 , cyclin D 3 , cdk 4 , p 16 ( INK4a ) , p 21 ( WAF 1 ) , p 27 ( KIP 1 ) , c myc , bcl 2 , and NPAT ) . ^^^ The growth inhibitory activity of p 16 ( INK4a ) seemed to be abrogated by enhanced expression of cyclin D 2 , cdk 4 , and c myc in one T cell line and overexpression of cyclin E in the second T cell line . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin D 1 , cdk 2 , and cdk 4 protein was also examined by Western blot . ^^^ Down regulation of cyclin D 1 , cdk 2 , cdk 4 protein correlated with telomerase activity ( p < 0 . 004 , p < 0 . 013 , and p < 0 . 001 respectively ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclin D 1 , cyclin E , cdk 4 and loss of heterozygosity of 8p , 13q , 17p in hepatocellular carcinoma : comparison study of childhood and adult hepatocellular carcinoma . ^^^ The expression of G 1 phase regulatory proteins ( cyclin D 1 , cyclin E and cdk 4 ) was studied using immunohistochemical methods . ^^^ No difference in cyclin E and cdk 4 expression was found between childhood and adult HCC . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis demonstrated that treatment with As2O3 ( 2 microM ) for 72 h did not change the steady state levels of CDK 2 , CDK 4 , cyclin D 1 , cyclin E , and cyclin B 1 but decreased the levels of CDK 6 , cdc 2 , and cyclin A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this study , we show that BMP 2 did not alter expression of cyclin D , cyclin E , cyclin dependent kinase 2 ( CDK 2 ) , CDK 4 , p27KIP1 , p16INK4a , or p15INK4b , but enhanced expression of p 21 ( CIP1 / WAF1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In highly expressing BC 3 cells the cyclin is complexed with cdk 6 , cdk 4 , cdk 2 , and cdk 5 under both latent and lytic conditions , although subtle changes in the level of cdk association are seen after induction of the lytic cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TP 53 alterations in relation to the cell cycle associated proteins p 21 , cyclin D 1 , CDK 4 , RB , MDM 2 , and EGFR in cancers of the uterine corpus . ^^^ In the present study , TP 53 alterations have been analysed and compared with the expression of the proteins p 21 , cyclin D 1 , cdk 4 , RB , EGFR , and MDM 2 in 53 cancers of the uterine corpus . ^^^ Immunohistochemically , there was an increased protein level of TP 53 in 77 per cent , p 21 in 36 per cent , cyclin D 1 in 45 per cent , cdk 4 in 77 per cent , EGFR in 8 per cent , and MDM 2 in 32 per cent of the cases . ^^^ Furthermore , there may be an association between TP 53 and p 21 ( p=0 . 038 ) and cyclin D 1 and cdk 4 ( p=0 . 045 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Entry of quiescent cells into the cell cycle is driven by the cyclin D dependent kinases Cdk 4 and Cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Measurement of DNA synthesis in platelet derived growth factor stimulated VSMC treated with DBcAMP revealed that cells became refractory to growth inhibition by 12 16 h , consistent with blockade in mid G 1 . cAMP treatment blunted the serum induced rise in cyclin D 1 during cell cycle progression without altering levels of the cyclin dependent kinase cdk 4 or cyclin E and its associated kinase , cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The decrease in cdk 4 activity was concurrent with reduced levels of cyclin D 3 protein and a decrease in the fraction of cdk 4 associated with cyclin D 3 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Alterations of p 53 , pRb , cyclin D ( 1 ) and cdk 4 in human oral and pharyngeal squamous cell carcinomas . ^^^ We have studied the expression of p 53 , pRb , cyclin D ( 1 ) and cdk 4 in 53 cases of oral and pharyngeal squamous cell carcinomas using immunohistochemistry . ^^^ In summary , our results suggest that inappropriate expression of p 53 , pRb , cyclin D ( 1 ) or cdk 4 is likely to contribute to the development of oral and pharyngeal cancers . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This delayed senescence may result from reduced association of p 16 with CDK 4 , reduced levels of underphosphorylated pRb , and steady levels of cyclin E and E2F1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In fact when they are overexpressed in the nucleus , cyclin D 3 , along with its kinase ( cdk 4 ) but not cyclin E is overexpressed even though cells are serum starved . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The activity of cdk complexes is regulated in part by the association of a cyclin partner that acts as a positive effector and by two families of cdk inhibitors , the kinase inhibitor proteins ( KIP ) and the inhibitors of cdk 4 ( INK 4 ) , which act as negative effectors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mitogen dependent , cyclin D dependent kinases ( cdk 4 and cdk 6 ) phosphorylate the retinoblastoma ( Rb ) tumor suppressor protein , helping to cancel its growth inhibitory effects and enabling E2F transcription factors to activate genes required for entry into the DNA synthetic phase ( S ) of the cell division cycle . ^^^ Lesions in the p 16 cyclin D CDK 4 Rb and ARF Mdm 2 p 53 pathways occur so frequently in cancer , regardless of patient age or tumor type , that they appear to be part of the life history of most , if not all , cancer cells . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Degradation is mediated through a previously unrecognized destruction box in cyclin D 1 and leads to a release of p21cip1 from CDK 4 to inhibit CDK 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The oncogenic role of reduced , but not absent , levels of p27KIP1 is supported by recent studies in murine models and evidence that this protein not only inhibits the activity of complexes containing CDK 2 and cyclin E , but also promotes the assembly and catalytic activity of CDK 4 or CDK 6 in complexes with cyclin D . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We did not observe consistent changes in protein levels of cyclin D , cyclin E , CDK 4 , CDK 6 , CDK 2 , p 27 ( Kip 1 ) , p 16 ( INK4a ) , or RNA levels of p 15 ( INK4b ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 and retinoblastoma proteins were induced following the mitogenic stimulation of both control and TSA treated cells , and cyclin D 1 formed complexes with CDK 4 under both conditions . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Re expression of myc activates the cell cycle without inducing apoptosis . myc triggers the expression of cyclin D 2 , cyclin E and Cdk 4 , followed by the activation of cyclin E associated kinase and hyper phosphorylation of Rb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Treatment of MCF 7 , T47D and SKBR 3 for 24 48 h with 3 microM HPR , a concentration attainable in vivo , resulted in growth inhibition and marked dephosphorylation of pRb involving Ser 612 , Thr 821 , Ser 795 and Ser 780 , target residues for cyclin dependent kinase 2 ( Cdk 2 ) the former two , and Cdk 4 the latter two . ^^^ The steady state levels of Cdk 2 , Cdk 4 and Cyclin A proteins were unaffected by HPR , while those of Cyclin D 1 were significantly reduced in all three cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As shown by immunoblot analysis , EGCG treatment of the cells resulted in significant dose and time dependent ( 1 ) upregulation of the protein expression of WAF1 / p21 , KIP1 / p27 , p 16 and p 18 , ( 2 ) downmodulation of the protein expression of cyclin D 1 , cdk 4 and cdk 6 , but not of cyclin E and cdk 2 , ( 3 ) inhibition of the kinase activities associated with cyclin E , cyclin D 1 , cdk 2 , cdk 4 and cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The p16ink4a cyclin D1 / cyclin dependent kinase 4 ( Cdk 4 ) retinoblastoma ( Rb ) pathway has emerged as a critical target in oncogenesis . ^^^ Expression of p16ink4a , cyclin D 1 , Cdk 4 , and Rb in relation to that of proliferating cell nuclear antigen was characterized in esophagi by immunohistochemistry at 0 , 24 , and 48 h , and 1 , 3 , 7 , 10 , and 14 weeks after NMBA treatment . ^^^ At the same time , overexpression of cyclin D 1 , Cdk 4 , and Rb was found in the corresponding lesion in adjacent esophageal sections . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In DROSOPHILA : , single genes for Cyclin D and Cdk 4 have been identified , simplifying genetic analysis . ^^^ Here , we show that DROSOPHILA : Cdk 4 interacts with Cyclin D and the Rb homolog RBF as expected , but is not absolutely essential . ^^^ Overexpression of inactive mutant Cdk 4 , which is able to bind Cyclin D , does not enhance the Cdk 4 mutant phenotype , confirming the absence of additional Cyclin D dependent cdks . ^^^ However , the growth of cells and of the organism is reduced in Cdk 4 mutants , indicating a role of D type cyclin dependent protein kinases in the modulation of growth rates . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclin dependent kinases ( cdks ) and cyclins , except cdk 4 , was generally suppressed in CD34+ cells freshly isolated from the bone marrow of healthy volunteers . ^^^ The behaviour of cell cycle control genes during haematopoietic differentiation was classified into four patterns : ( 1 ) universal upregulation ( cdc 2 , cdk 2 , cyclin A , cyclin B and p 21 ) ; ( 2 ) upregulation in specific lineages ( cyclin D 1 , cyclin D 3 and p 15 ) ; ( 3 ) no induction or stable expression ( cdk 4 , cyclin D 2 , cyclin E and p 27 ) ; and ( 4 ) universal downregulation ( p 16 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , E , A , H , Cdk 1 ( cyclin dependent kinase ; Cdc 2 ) , Cdk 4 , and Cdk 6 protein levels were determined by Western blot analysis at different pathologic stages of liver tissues exhibiting HCC . ^^^ Enzymatic activities of cyclin D 1 , E , A , Cdk 4 , Cdk 6 , Cdc 2 , Cdk 7 , and Wee 1 kinase were measured by in gel kinase assay . ^^^ Protein levels and kinase activities of cyclin D 1 , E , Cdk 4 , cyclin A , and Wee 1 increased proportionally with the development of HCC , especially in the transition process from chronic hepatitis to HCC . ^^^ These data suggest that the increase in Cdc 2 kinase may play a role in the process from normal liver to chronic hepatitis , whereas the predominant increase in cyclin D 1 , Cdk 4 , cyclin E , cyclin A , and Wee 1 suggests involvement not only in the process from normal liver to chronic hepatitis , but also during transition into HCC . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Inhibition of cdk 4 kinase activity late in differentiation resulted from events other than p 27 ( Kip 1 ) binding or loss of cyclin D from the complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Importantly , CDK 6 can not substitute for CDK 4 in this role , which demonstrates that the 2 cyclin D dependent kinases are functionally different . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The tumour suppressor gene p16 / INK4a encodes a specific inhibitor of the cyclin D dependent kinases CDK 4 and CDK 6 . p16 / INK4a prevents the association of CDK 4 with cyclin D 1 , and subsequently inhibits phosphorylation of retinoblastoma tumour suppressor protein ( pRb ) , thus preventing exit from the G 1 phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of tumor derived mutations has led to the suggestion that p16INK4a , cyclin D 1 , cdk 4 , and the retinoblastoma protein ( pRB ) are components of a regulatory pathway that is inactivated in most tumor cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Downregulation of cyclin D 1 alters cdk 4 and cdk 2 specific phosphorylation of retinoblastoma protein . ^^^ Levels of cdk 2 , cdk 4 , and cdk 6 decreased 40 70 % , while levels of cyclin A and B were unaffected by induction of CD 1 antisense . ^^^ Induction of a CD 1 antisense gene in a human colon cancer cell line resulted in rapid , concomitant changes in CD 1 mRNA and protein , cyclin E , cdk 2 , cdk 4 , and cdk 6 , as well as the ratio of ppRb to pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This effect was associated with a decrease in cyclin dependent kinase ( Cdk ) 2 and , to a lesser extent , Cdk 6 , but not Cdk 4 activity , without changes in Cdk 2 , 4 , and 6 and cyclin D and E protein levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of pRb , cyclin D 1 , cdk 4 , cyclin E , cdk 2 , E2F1 and DP 1 was determined in MCF 7 and MDA MB 468 breast carcinoma cells , H 460 and Calu 6 non small cell lung carcinoma cells , H 82 and SW 2 small cell lung carcinoma cells , HCT 116 and HT 29 colon carcinoma cells and LNCaP and DU 145 prostate carcinoma cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A higher concentration of YTA 0040 down regulated the levels of expression of CDK 2 , CDK 4 , cyclin D 1 and cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In p 27 ( kip 1 ) p 21 ( cip 1 ) deficient cells , the cyclin D 3 pool consisted primarily of cyclin D 3 monomers , whereas in wild type cells , the majority of cyclin D 3 molecules were complexed to cdk 4 and either p 27 ( kip 1 ) or p 21 ( cip 1 ) or were monomeric . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In T cells and fibroblasts Tax enhances the activity of the cyclin dependent kinases ( CDK ) CDK 4 and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We found that the expression of cyclin A and p 21 ( WAF 1 ) molecules was primarily modulated by TGFbeta 1 treatment while the expression of other regulatory components , like cyclins D , cyclin E , cdk 2 , cdk 4 , and cdk 6 or p 15 ( INK4B ) , p 16 ( INK4A ) , and p 27 ( KIP 1 ) was not significantly affected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Up regulation of cyclin dependent kinases ( Cdk 4 and Cdk 6 ) and cyclin D 3 was initiated in TCR stimulated T cells entering G1A phase and expression of these markers steadily increased as T cells progressed from G1A into G1B phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
By Western blot analysis , we demonstrated that cyclin D 3 and CDK 4 protein but not other G0 / G1 phase regulatory protein levels were decreased by ketoconazole treatment in both COLO 205 and HT 29 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The binding of CDK 2 , CDK 4 , or proliferating cell nuclear antigen to p 21 ( WAF 1 ) and its subcellular localization were unchanged in the presence or absence of IL 3 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
While p15INK4B and its binding to both cdk 4 and cdk 6 increased with increasing passage , some cyclin D 1 bound cdk 4 and cdk 6 persisted in senescent cells , whose inhibition could not be attributed to p15INK4B . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To determine the crucial abnormality in the cell cycle regulatory proteins in human squamous cell carcinoma of the esophagus , we examined the cell growth ratio ( CGR ) and basal expression levels of G 1 cyclins ( cyclin D 1 , cyclin E ) , cyclin dependent kinase ( cdk ) 2 , cdk 4 , proliferating cell nuclear antigen ( PCNA ) , and p21Waf 1 using 9 cell lines ( KE 3 , KE 4 , TE 8 , TE 9 , TE 10 , TE 11 , YES 1 , YES 2 , and YES 6 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Binding of the elevated p 27 protein to cyclin E , cdk 2 and cdk 4 , however , was not impaired , suggesting that this cell cycle suppressor protein is functional . ^^^ In addition , cyclin D 1 , cdk 2 , cdk 4 and cyclin E associated kinase activities were also lower in these estrogen induced renal neoplasms than in untreated , age matched kidneys . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , lack of adhesion to substratum decreased cyclin H but not cdk 7 with accumulation of a slower migrating , presumably unphosphorylated cdk 4 isoform . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We now identify 22 in vivo phosphorylation sites of p 130 , targeted by diverse kinases , and present evidence for three cyclin dependent kinase 4 ( 6 ) [ Cdk 4 ( 6 ) ] specific phosphorylations , which appear critical for controlling the growth restraining activity of p 130 . ^^^ Experiments using p 130 ( Delta ) ( Cdk 4 ) and another phosphorylation deficient mutant , p 130 ( PM19A ) , with 19 phosphorylation sites mutated , revealed that the p 130 imposed G 1 block reflects cooperative growth suppressive effects of phosphorylation regulated E2F binding and phosphorylation independent sequestration of cyclin E ( A ) Cdk 2 through the N terminal cyclin binding motif of p130 . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Retinal cellularity was rescued in the cyclin D 1 null mouse by loss of p 27 with only a partial restoration of phosphorylation of retinoblastoma protein ( Rb ) and Cdk 4 activity but with a dramatic elevation of Cdk 2 activity . ^^^ Our data provide in vivo genetic validation of cell culture experiments that indicated that p 27 acts as a negative regulator of cyclin E Cdk 2 activity and that it can be titrated away by cyclin D Cdk 4 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We report the following results . ( 1 ) Wild type ICP 0 activates cyclin D dependent kinase 4 ( cdk 4 ) and stabilizes cyclin D 1 although ICP 0 does not interact with this cyclin . ( 2 ) The D199A mutant virus ( R 7914 ) does not activate cdk 4 or stabilize cyclin D 1 , and neither the wild type nor the mutant virus activates cdk 2 . ( 3 ) Early in infection of human embryonic lung ( HEL ) fibroblasts both wild type and D199A mutant ICP0s colocalize with PML , and in these cells the ND 10 nuclear structures are dispersed . ^^^ These studies suggest the following conclusions . ( 1 ) ICP 0 brings to the vicinity of ND 10 cyclin D 3 and , in consequence , an activated cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , cyclin E , CDK 2 and CDK 4 , did not change during treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The protein level of cyclin D 1 decreased without any apparent change in the amounts of Cdk 2 , Cdk 4 , cyclin E or cyclin A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We investigated the role of proteins involved in the cell cycle , including cyclin D 1 , cyclin dependent kinase 4 ( cdk 4 ) , and cyclin dependent kinase inhibitors p 21 and p 27 in blood vessels of angiotensin 2 infused rats and the effect therein of the AT ( 1 ) receptor antagonist losartan . ^^^ The expression of cyclin D 1 , cdk 4 , p 21 , and p 27 , which play critical roles during the G ( 1 ) phase of the cell cycle process , was examined by Western blot analysis . ^^^ Expression of cyclin D 1 and cdk 4 was significantly increased in the angiotensin 2 group to 213 . 7+ / 8 % and 263 . 6+ / 37 % of control animals , respectively , whereas expression of p 21 and p 27 was significantly decreased in the angiotensin 2 group to 23 . 2+ / 10 . 4 % and 10 . 3+ / 5 . 3 % of control animals , respectively . ^^^ Thus , when AT ( 1 ) receptors are stimulated in vivo , DNA synthesis is enhanced in blood vessels by activation of cyclin D 1 and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
No changes in the levels of cyclin E or the catalytic partners of these cyclins , CDK 2 , CDK 4 , or CDK 6 , were observed . ^^^ The levels of cyclin E and CDK 4 , however , were similar to the control cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Immunohistochemistry was used to analyse 49 primary cutaneous malignant melanomas , 18 metastatic melanomas , and 12 histologically confirmed naevus cell naevi for their expression of cyclins ( A , B 1 , D 1 , D 2 , D 3 , and E ) and cyclin dependent kinases ( CDK 1 , CDK 2 , and CDK 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although cyclin D 2 cyclin dependent kinase 4 ( cdk 4 ) complexes mediate early retinoblastoma gene product ( pRb ) phosphorylation in B 1 cells , the transient nature of their accumulation can not account for the continued increase in pRb phosphorylation , which is maximal at 24 h . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
BACKGROUND : Cyclin dependent kinase 4 ( Cdk 4 ) represents a prime target for the treatment of cancer because most human cancers are characterized by overexpression of its activating partner cyclin D 1 , loss of the natural Cdk 4 specific inhibitor p 16 , or mutation ( s ) in Cdk 4 ' s catalytic subunit . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have already reported the alteration of CDK 4 and cyclin D 1 expression in oral cancer . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A potent inhibitor of the cyclin D dependent kinases CDK 4 and CDK 6 . ^^^ Progression through the G 1 phase of the cell cycle requires phosphorylation of the retinoblastoma gene product ( pRb ) by the cyclin D dependent kinases CDK 4 and CDK 6 , whose activity can specifically be blocked by the CDK inhibitor p 16 ( INK4A ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 represses STAT 3 activation through a Cdk 4 independent mechanism . ^^^ This effect was not shared by cyclin E , was independent of association with Cdk 4 , and was unaffected by inhibitors of Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To compare the expression status of G 1 cyclins , these EBV associated lymphoma lines ( 6 EBV [ ] human SCID mouse lymphoma lines , 13 human B cell lymphomas and 8 samples of human tonsil tissue ) were examined by reverse transcription polymerase chain reaction Southern blotting , Western blotting and immunohistochemistry . mRNA expression of cyclin D 1 ( CCND 1 ) , cyclin D 2 ( CCND 2 ) , cyclin E ( CCNE ) , cyclin dependent kinase 2 ( CDK 2 ) and 4 ( CDK 4 ) was found in all 3 types of lymphomas . ^^^ Immunoprecipitation of EBV ( + ) and ( ) SCID mouse lymphomas for CCND 1 , CCND 2 and CCNE vs . p 21 , PCNA and CDK 2 or CDK 4 demonstrated that , in EBV ( + ) SCID lines , CCND2 / CDK4 complexes were present without binding to p 21 , suggesting independence from p 21 regulation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We screened a cohort of 206 patients with clinically localized PC treated with radical prostatectomy for overexpression of the INK4A gene , the product of which inactivates the G 1 phase cyclin dependent kinases , Cdk 4 and Cdk 6 . p16INK4A protein expression was evaluated by immunohistochemistry in areas of high grade intraepithelial neoplasia ( HGPIN ) , a precursor to invasive disease , and of cancer in the same specimen . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
G3DeltaEGF transfected cells formed smaller colonies , arrested cell cycle at G ( 1 ) phase , inhibited expression of cell cycle proteins cdk 4 and cyclin D 1 , and contained multiple nucleoli . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Apigenin reduced the protein levels of CDK 4 , cyclins D 1 and A , but did not affect cyclin E , CDK 2 and CDK 6 protein expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RT PCR analysis showed that cyclin D 2 , cyclin D 3 , CDK 4 , and CDK 6 were ubiquitously expressed in normal B cell development and in the BLIN ALL cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Of the cell cycle control proteins , PCNA , Cdk 2 , and cyclin A were detected at high concentrations ; cdc 2 , Cdk 4 , and cyclin B were detected at very low concentrations ; while cyclin D 1 , cyclin D 3 , Cip 1 , and Kip 1 were not detected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Alteration of cyclin D 1 and CDK 4 gene in carcinoma of uterine cervix . ^^^ Amplification and overexpression of cyclin D 1 and CDK 4 genes in cervical carcinoma were studied by semi quantitative differential polymerase chain reaction assay and an immunostaining technique , respectively . ^^^ Amplifications of cyclin D 1 and CDK 4 genes were found in 24 % ( 27 / 113 ) and 26 % ( 29 / 112 ) of tumors , respectively . ^^^ Overexpression of cyclin D 1 and CDK 4 was demonstrated in 32 % ( 21 / 66 ) and 73 % ( 45 / 62 ) of tumors , respectively . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TRIP Br 1 is identical to the cyclin dependent kinase 4 ( cdk 4 ) binding protein p 34 ( SEI 1 ) , which renders the activity of cyclin D / cdk4 resistant to the inhibitory effect of p 16 ( INK4a ) during late G ( 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The immunoblot analysis revealed that resveratrol treatment causes a dose and time dependent ( a ) induction of WAF1 / p21 ; ( b ) decrease in the protein expressions of cyclin D 1 , cyclin D 2 , and cyclin E ; and ( c ) decrease in the protein expressions of cdk 2 , cdk 4 , and cdk 6 . ^^^ Taken together , our study suggests that resveratrol treatment of the cells causes an induction of WAF1 / p21 that inhibits cyclin D1 / D2 cdk 6 , cyclin D1 / D2 cdk 4 , and cyclin E cdk 2 complexes , thereby imposing an artificial checkpoint at the G ( 1 ) > S transition of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , the cyclin D 2 partner CDK 4 was increased in 41 % ( 21 of 51 ) of all tumors by a factor of 6 , most strongly in embryonal carcinomas . ^^^ Statistical analysis using configural frequency analysis and regression analysis revealed that cyclin D 2 and CDK 4 expression were strongly correlated ( r ( 2 ) = 0 . 682 ; P = 0 . 000052 ) , whereas expression of CDK 6 did not correlate with either of them ( r ( 2 ) = 0 . 382 ; P = 0 . 00085 ) . ^^^ Western blots and immunohistochemical experiments confirmed cyclin D 2 and CDK 4 overrepresentation and reduced expression of cyclin E and CDK 2 tumors in the few tumors under protein study . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mammalian cells require a cyclin D dependent kinase for the cell cycle start , yet many mesenchymal cells express three seemingly redundant D cyclins and similarly , seemingly redundant Cdk 4 and Cdk 6 as their kinase partners . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Introduction of Tax into resting Kit 225 cells induced activation of the G1 / S transition regulation cascade consisting of activation of cyclin dependent kinase 2 ( CDK 2 ) and CDK 4 , phosphorylation of the Rb family proteins and an increase in free E2F . ^^^ The kinase activation was found to result from Tax induced expression of genes for cell cycle regulatory molecules including cyclin D 2 , cyclin E , E2F1 , CDK 2 , CDK 4 and CDK 6 , and Tax induced reduction of CDK inhibitors p 19 ( INK4d ) and p 27 ( Kip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the first mechanism , cyclin D 1 mRNA promptly disappeared within 1 min after UV irradiation , although cdk 4 mRNA levels were unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RESULTS : In normal colonic epithelium , cyclin D 2 was undetectable ; expression of cyclin D 1 , CDK 4 , and pRB correlated with proliferation ; and p 16 , p 18 , p 19 , and cyclin D 3 were most abundant in quiescent , differentiated cells . ^^^ Elevated cyclin D 1 , D 2 , and CDK 4 correlated with enhanced dysplasia . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Northern blot analyses demonstrate that cyclin dependent kinase 4 ( Cdk 4 ) and cyclin D 2 mRNA levels are elevated , and immunohistochemistry shows that p 27 protein levels are decreased in both ovarian and testicular tumors from Inha ( / ) mice . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression and significance of cell cycle related proteins Cyclin Dl , CDK 4 , p 27 , E2F l and Ets 1 in chondrosarcoma of the jaws . ^^^ To elucidate the expression and significance of cell cycle associated proteins in chondrosarcoma of the jaws , Cyclin Dl , CDK 4 , p 27 , E2F l and Ets l expressions were examined in chondrosarcoma and osteochondroma of the jaws by immunohistochemical ABC method . ^^^ The results demonstrated that Cyclin Dl , CDK 4 , p 27 , E2F 1 and Ets 1 were positive 75 % ( 15 of 20 ) , 60 % ( 12 of 20 ) , 25 % ( 5 of 20 ) , 65 % ( 13 of 20 ) and 60 % ( 12 of 20 ) in chondrosarcoma of the jaws , respectively . ^^^ In addition , the positive rate of Cyclin Dl , CDK 4 , E2F l and Ets 1 proteins was significantly higher , whereas p 27 was lower in chondrosarcoma than in osteochondroma of the jaws ( P < 0 . 05 ) . ^^^ These data show that the expression of cell cycle regulatory proteins is altered in chondrosarcoma of the jaws : cyclin Dl , CDK 4 , E2F 1 and Ets 1 are over expressed and p 27 is low expressed . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The association of cyclin D 1 with Cdk 4 , the kinase activity of Cdk 4 against pRb in vitro , the nuclear localization of cyclin D 1 , and the stability of cyclin D 1 were all severely impaired in p 27 ( / ) mammary epithelial cells compared with p 27 ( + / + ) and p 27 ( + / ) mammary epithelial cells . ^^^ Therefore , p 27 is required for mammary gland development in a dose dependent fashion and positively regulates cyclin D Cdk 4 function in the mammary gland . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 and its catalytic partner CDK 4 are known to play important roles in the G1 / S checkpoint of the cell cycle . ^^^ The complex formed by CDK 4 and cyclin D 1 has been strongly implicated in the control of cell proliferation and prognoses in human malignancies . ^^^ We investigated the immunohistochemical expression of cyclin D 1 , CDK 4 and proliferating cell nuclear antigen ( PCNA ) in 102 patients with laryngeal squamous cell carcinoma ( LSCC ) . ^^^ Cyclin D 1 and CDK 4 expression was significantly associated with cell proliferation measured by PCNA ( r = 0 . 812 , p < 0 . 0001 and r = 0 . 725 , p < 0 . 0001 , respectively ) . ^^^ When cyclin D 1 and CDK 4 are combined , the patients with co overexpression of cyclin D 1 CDK4 revealed the poorest overall survival . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Neither cyclin D 1 , nor MDM 2 and CDK 4 amplification was observed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In Ewing cell lines , cyclin D 1 , CDK 4 , Rb , p27KIP1 and c Myc were consistently highly expressed whereas p57KIP2 , p15INK4B and p14ARF demonstrated undetectable or low expression levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This effect was associated with reduced cyclin dependent kinase ( cdk 4 and cdk 2 ) activities with no alterations in CDK protein levels . ^^^ Serum stimulation of control cells resulted in reduction in the p 27 content in the cyclin E cdk 2 complex and its accumulation in the cyclin D 1 cdk 4 complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , forced expression of cyclin D 1 and wild type or dominant negative cdk 4 in myotubes restores physiological levels of cdk 4 kinase activity , allowing progression through the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Twenty four hour exposure of exponentially growing MCF 7 cells to 1alpha , 25 dihydroxyvitamin D ( 3 ) impeded proliferation by preventing S phase entry , an effect that correlated with appearance of the growth suppressing , hypophosphorylated form of the retinoblastoma protein ( pRb ) , and modulation of cyclin dependent kinase ( cdk ) activities of cdk 4 , 6 , and 2 . ^^^ While the observed 10 fold inhibition of cyclin D1 / cdk 4 associated kinase activity appeared independent of cdk inhibitors , the activity of cdk 2 decreased about 20 fold , reflecting joint effects of the lower abundance of its cyclin partners and a significant increase of the cdk inhibitor p 21 ( CIP1 / WAF1 ) , which blocked the remaining cyclin A ( E ) / cdk 2 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Raf activation increased the expression of Cdk 2 , Cdk 4 , cyclin A , cyclin D , cyclin E , p 21 ( Cip 1 ) and c Myc and decreased the expression of p 27 ( Kip 1 ) which are associated with G ( 1 ) progression . ^^^ The cell clones with the highest Delta Raf activity , FD / Delta B Raf : ER , underwent apoptosis before cell proliferation . p 21 ( Cip 1 ) induced by Raf activation specifically bound with Cdk4 / cyclin D complexes but not Cdk2 / cyclin E complexes and this binding was associated with the increased Cdk 4 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Therefore , to determine their overall contribution we have simultaneously examined the immunohistochemical status of pRb , p 16 and cyclin D 1 and analysed the CDK 4 gene for a characterized activating mutation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The inhibitory effect of glycolic acid on UV induced tumor development was accompanied by decreased expression of the following UV induced cell cycle regulatory proteins : proliferating cell nuclear antigen ( PCNA ) , cyclin D 1 , cyclin E , and the associated subunits cyclin dependent kinase 2 ( cdk 2 ) and cdk 4 . ^^^ The decreased expression of the cell cycle regulatory proteins PCNA , cyclin D 1 , cyclin E , cdk 2 , and cdk 4 and the signal mediators JNK , p 38 kinase , and MEK may play a significant role in the inhibitory effect of glycolic acid on UV induced skin tumor development . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This activity of Msx 1 is associated with its ability to upregulate cyclin D 1 expression and Cdk 4 activity , while Msx 1 has minimal effects on cellular proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here , we discuss how estrogens exert control over several key G 1 phase cell cycle regulators , namely cyclin D 1 , Myc , Cdk 2 , Cdk 4 , Cdk inhibitors and Cdc25A . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here , we show that gamma irradiated murine myeloid 32D cells arrest in G ( 1 ) with active cyclin D cyclin dependent kinase 4 ( Cdk 4 ) but with inactive cyclin E Cdk 2 kinases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
On laminin , endothelial cells fail to translate Cyclin D 1 mRNA and activate CDK 4 and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Extracellular signal regulated protein kinase ( p44 / p42 ERK ) activity and expressions of cell cycle proteins ( cyclin D ( 1 ) , CDK 4 , pRB and p 27 ( Kip 1 ) ) were determined by Western blotting . ^^^ PDGF induced elevated protein levels of cyclin D ( 1 ) , but the CDK 4 protein level did not change . ^^^ Dipyridamole and DBcAMP had no effect on the levels of cyclin D ( 1 ) and CDK 4 in PDGF stimulated HPMC . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We found that GL 331 had no inhibitory effect on the expression of cyclins E , A , B 1 , CDK 4 , and CDK 2 ; instead , its cell growth inhibitory effect was partly attributable to an early down regulation of cyclin D 1 expression and in turn the reduction of retinoblastoma protein phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , we made an immunohistochemical investigation of cyclin D 1 and cdk 4 , which are involved in the Rb pathway . ^^^ The labeling index of pRb expression in cases with carcinoma was significantly decreased compared with that in cases with a premalignant lesion ( P < 0 . 01 ) , while the labeling index of cyclin D 1 and cdk 4 increased gradually during the course of carcinogenesis . ^^^ In conclusion , a decrease of pRb and an increase of cdk 4 and cyclin D 1 were shown to occur during the premalignant stage . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , high levels of cyclin E , cdk 2 , and cdk 4 correlated with weak / absent ER expression , and p 16 and p 21 overexpression was significantly associated with low PR immunoreactivity . ^^^ Cyclin B 1 expression correlated with cyclin E , cdk 2 , cdk 4 , p 21 , Rb , and Ki 67 , and cyclin E expression with cyclin D 1 and Rb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression levels of the AP 1 factors were correlated with clinico pathologic tumor parameters , steroid receptor status , Ki 67 expression and the expression levels of eight cell cycle regulatory proteins ( cyclin D 1 , cyclin E , cyclin B 1 , cdk 2 , cdk 4 , p 16 , p 21 , and Rb ) . ^^^ These factors also correlated significantly with cell cycle promoters ( c fos with cyclin E , cyclin B 1 , cdk 2 , and cdk 4 ; fra 2 with cyclin B 1 ; and junB with cyclin D 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , senescence is associated with increased binding of the cyclin dependent kinase inhibitor ( CDK 1 ) p 16 ( INK4a ) to CDK 4 , down regulation of cyclin E protein levels ( and consequent loss of cyclin E / CDK2 activity ) , underphosphorylation of the retinoblastoma protein RB and subsequent increased levels of E2F4 RB repressive complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Earlier , we have shown that resveratrol treatment results in an induction of the cyclin kinase inhibitor WAF1 / CIP1 / p21 which , by inhibiting cyclin ( E , D 1 , and D 2 ) and cyclin dependent kinases ( cdk 2 , cdk 4 , and cdk 6 ) , results in a G0 / G1 phase arrest followed by apoptosis of A 431 human epidermoid carcinoma cells ( Ahmad et al . , Clin . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We concluded that AGE induced cell cycle dependent cellular proliferation by inducing the JAK 2 STAT5 cyclin D 1 and cdk 4 pathways in NRK 49F cells . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In a genetic screen , we identified mutations in cyd 1 cyclin D and cdk 4 Cdk4 / 6 . ^^^ To investigate whether cyd 1 and cdk 4 solely act to overcome G 1 inhibition by retinoblastoma family members , we constructed double mutants that completely eliminate the function of the retinoblastoma family and cyclin D Cdk4 / 6 kinases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TGF beta 1 arrested cells in G 1 phase and significantly downregulated the expression of cyclin D 2 , cyclin D 3 , cdk 4 , cyclin A , and cdk 2 . ^^^ Although treatment of cells with TGF beta 1 up regulated accumulation of p 27 ( kip 1 ) in both nucleus and cytoplasm , the association of the p 27 ( kip 1 ) with cdk 2 , cyclin A , cyclin D 2 , cyclin D 3 , and cdk 4 was markedly down regulated , suggesting that p 27 ( kip 1 ) is not responsible for the downregulation of the kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
An increase in cyclin dependent kinase 2 ( cdk 2 ) protein expression occurred after 12 h , but no changes in cdk 4 or cdk 6 protein levels were observed . ^^^ The increase in cyclin D 1 , E , and A protein expression was associated with an increase in cyclin D 1 cdk 4 , cyclin E cdk 2 , and cyclin A cdk 2 complex formation . p 53 protein expression was elevated through 48 h , and the cdk inhibitor protein p 21 ( Cip1 / WAF1 ) was elevated 6 fold to 7 . 5 fold between 12 and 24 h . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Finally , we show that transient , ectopic expression of cyclin D 1 results in reduced cell cycle progression in androgen dependent LNCaP cells independent of CDK 4 association . ^^^ Collectively , our data support a model wherein cyclin D 1 has a mitogenic ( CDK 4 dependent ) function and an anti mitogenic function ( dependent on regulation of the AF 1 domain ) that can collectively control the rate of androgen dependent cellular proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In order to explore the role of 16alpha OHE ( 1 ) in cell cycle regulation , we examined its effects on cyclins ( D 1 , E , A , B 1 ) , cyclin dependent kinases ( Cdk 4 , Cdk 2 ) , and retinoblastoma protein ( pRB ) using Western and Northern blot analysis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A particular role in the regulation of these phenomena is played by proteins involved in early G 1 phase regulation : pRb kinases : cyclin dependent kinases ( cdk ) : cdk 4 and cdk 6 activated by cyclins D , and universal cdk inhibitor p 27 ( Kip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cyclin dependent kinase inhibitor p21WAF1 / Cip1 is an antiestrogen regulated inhibitor of Cdk 4 in human breast cancer cells . ^^^ Through time course analysis , we demonstrate that changes in Cdk 4 activity in response to estrogen or antiestrogen treatment do not correlate directly with cyclin D 1 protein levels or association . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Regulation of Cdk 4 , cyclin E and Cdk 2 protein levels was also not different . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
By flow cytometry and by immunofluorescence , only cells overexpressing cdk 4 or cyclin D 1 underwent apoptosis , which was not associated with G 1 arrest . ^^^ Cdk 4 kinase activity was significantly higher in cdk 4 , or cyclin D 1 expressing cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Freshly isolated MyrAkt thymocytes express high levels of cyclins D 2 and E and cdk 4 but lower than normal levels of cyclin D 3 and cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Quercetin treatment , however , resulted in a moderate increase in Cip1 / p21 with no change in Kip1 / p27 and a decrease in CDK 4 and cyclin D 1 . ^^^ EGCG treatment also led to an induction of Cip1 / p21 but no change in Kip1 / 27 , CDK 2 , and cyclin D 1 and a decrease in CDK 4 only at low doses . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression and precipitation of tagged gankyrin from cultured cells detects a complex containing co transfected tagged S 6 ATPase ( or endogenous S 6 ) and endogenous cyclin D dependent kinase CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Whereas MSA had no effect on total levels of the cyclin dependent kinase ( CDK ) 4 , the amount of CDK 4 immunoprecipitated with cyclin D 1 in MSA treated cells was decreased as was the kinase activity of the immunoprecipitated complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
P 19 ( INK4d ) is a tumor suppressing protein and belongs to a family of cyclin D dependent kinase inhibitors of CDK 4 and CDK 6 , which play a key role in human cell cycle control . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Examination of cyclin box mutants shows that repression is unrelated to Cdk 4 activation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Of the analyzed proliferative factors PCNA , cyclin A , cyclin D , cdk 2 , cdk 4 and cell cycle phases only cyclin D , cdk 4 and the cell cycle phases were up regulated in growing carcinomas . ^^^ The expression of JUN , N RAS , FOS , cyclin D , and cdk 4 were significantly different in both groups with non overlapping confidence intervals . ^^^ Thus , the up regulation of the proteins JUN , N RAS , FOS , cyclin D and cdk 4 predicts the growth of NSCLC in nude mice . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Recent biological studies of Cyclin D1 / Cdk4 have proposed that p 21 C terminal domain ( p 21 ( CT ) ) plays a key role as a potent Cdk 4 inhibitor . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the regulatory effect of bombesin on the growth of immortalized human gastric epithelial cell line GES 1 , as well as on the cell cycle regulating elements cyclin D 1 and CDK 4 . ^^^ The growth effect was evaluated by MTT method , cyclin D 1 expression by flow cytometry , CDK 4 expression by Western blot plus enhanced chemoluminescence and CDK 4 activity by immunoprecipitation with antibody coated Sepharose beads . ^^^ CONCLUSION : In an immortalized human gastric epithelial cell line , bombesin promotes cell cycle progression via an increase in the expression of cyclin D1 / CDK4 and CDK 4 activity . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Recent evidence strongly suggest that the D type cyclins with cdk 4 and cdk 6 form holoenzymes that regulate cell cycle events earlier in G 1 than cyclin E / cdk2 complexes which functions near the G1 / S transition . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Among the various cell cycle molecules examined , coordinate expression and functional association of cyclin D 3 with cdk 4 suggest a role for proliferation and , that of cyclin D 3 with p 21 and cdk 6 is consistent with the development of polyploidy during stromal cell decidualization . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The levels of cyclin D 1 expression and the CDK 4 kinase activity were also significantly reduced . pRB was hypophosphorylated by sodium arsenite . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunoblotting demonstrated that cyclin dependent kinases ( cdk ) 2 and 6 , as well as cdc 2 were expressed at steady state levels , whereas cyclin D 1 , cyclin B 1 and cdk 4 were downregulated . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Administration of DEN for a period of one month showed an upregulation of cell cycle regulatory proteins namely cyclin D 1 , CDK 4 , cyclin E and CDK 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
TGF beta 1 intensified the decreased expression of CDK 2 , CDK 4 , CDK 6 and cyclin D 1 in EB 1089 treated NCI H 929 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Using a series of cell lines derived from oral squamous cell carcinomas ( SCCs ) that were not subjected to radiation or chemotherapy treatment , we detected specific hyperactivity of cyclin dependent kinase ( cdk ) 6 but not cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
By means of immunohistochemistry and quantitative real time PCR analysis , we detected protein expression of PCNA , bcl 2 , CDK 4 , p 53 and MDM 2 in both our cases and MDM 2 amplification in our second case . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , cdk 2 , and cdk 4 kinase activities were decreased in G 1 arrested and differentiated oligodendrocytes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Both STI 571 and LY 294002 lead to a decrease in the activity of cdk 4 kinase activity and a decrease in expression of both Cyclin D 2 and Cyclin E within several hours . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Basic fibroblast growth factor ( bFGF ) , FGF receptor , vascular endothelial growth factor ( VEGF ) and inducible nitric oxide synthase ( iNOS ) were also up regulated in this cell line . p 16 , p 53 , cdk 4 and cyclin D 1 could be detected in the cells and their indices were 43 . 1 % + / 11 . 2 % , 20 . 7 % + / 6 . 6 % , 33 . 1 % + / 11 . 4 % and 29 . 2 % + / 4 . 7 % respectively . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The CDK 4 and PCNA levels were evaluated and the response to genotoxic agents were observed . ^^^ Both levels of CDK 4 and PCNA were decreased . ^^^ This may have been achieved through lowering of CDK 4 or PCNA levels and not involving the apoptosis mechanism . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : ( 3 ) H TdR incorporation and cell counting for the assay of cell growth ; dot blot , in situ hybridization , and immunohistochemical methods for analysing the expression of cyclin D 1 and cycle dependent kinase 4 ( CDK 4 ) genes . ^^^ On the contrary , TGFbeta ( 1 ) treated cells decreased the expression of CDK 4 mRNA ) , CDK 4 as well as the cyclin D 1 proteins ( P < 0 . 05 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To further define the mechanism of the effect and determine the viral gene product ( s ) responsible , we examined various mutant viruses for their effects on cell cycle regulatory proteins ( pRb , cyclin D 1 , and cdk 4 ) and on cell cycle progression into S phase . ^^^ Furthermore , ICP 27 , ICP 4 , ICP 0 , and vhs were required for blocking the induction of the G 1 cell cycle regulators cyclin D 1 and cdk 4 in HSV infected cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , ErbB 2 or cyclin D 1 overexpressing p 27 ( / ) cells displayed reduced proliferation , anchorage independent growth , Cdk 4 activity , cyclin D 1 expression , and cyclin D 1 nuclear localization compared to wild type cells . ^^^ A cyclin D 1 mutation in its nuclear export sequence ( T286A ) partially rescued nuclear localization of cyclin D 1 in p 27 ( / ) cells but did not increase proliferation or Cdk 4 kinase activity . ^^^ However , MMTV neu / p27 ( / ) glands showed decreased proliferation , cyclin D 1 expression , and Cdk 4 activity , as well as markedly prolonged tumor latency , compared to MMTV neu / p27 ( + / + ) glands . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Taken together , these data indicate that p 107 is inactivated by cyclin D1 / Cdk4 via direct phosphorylation and that the RXL motif of p 107 plays a role in its inactivation by Cdk 4 in the absence of stable binding . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Moreover , immune complexes consisting of cyclin D 2 and cdk 4 or cyclin D 3 and cdk 4 were both functional and phosphorylated the RB protein in vitro . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Hyposmosis dramatically decreased Cdc 2 , Cdk 2 , Cdk 4 , cyclin B 1 , and cyclin D 3 expression in a time dependent fashion , in association with an overall decrease in cellular protein synthesis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Gene array analysis suggested that c Myc , cyclin C , proliferating cell nuclear antigen , cyclin dependent kinase ( cdk ) 1 , cdk 2 , cdk 4 , cyclin B and cyclin D 2 mRNA levels were lower in selenium deficient cells than in the cells supplemented with 0 . 25 micromol / L selenomethionine . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D type cyclins bind cyclin dependent kinases ( Cdk 4 and Cdk 6 ) and are expressed during the transition from G 0 into the S phase . ^^^ Cyclin D 3 levels were not altered by fasting and refeeding ; however , Cdk 4 expression was suppressed by fasting and returned to control levels after refeeding . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
DESIGN : The p 53 and Rb cyclin D pathways were investigated by immunohistochemical studies of p 53 , mdm 2 , pRb , p 16 , cyclin D 1 , and cdk 4 proteins , respectively . ^^^ Fourteen ( 21 % ) and 64 ( 96 % ) cases demonstrated cyclin D 1 or cdk 4 expression , respectively . ^^^ There was no correlation between pRb , p 16 , cyclin D 1 , or cdk 4 and tumor grade or relapse . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The Cyclin D Cdk 4 , 6 / INK4 / Rb / E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli . ^^^ This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D 1 , Cdk 4 , INK4a and INK4b , pRb etc . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D cdk 4 is not a master regulator of cell multiplication in Drosophila embryos . ^^^ Therefore , we have analyzed whether the developmentally controlled inactivation of Cyclin E Cdk 2 required for the epidermal cell proliferation arrest occurs as a consequence of Cyclin D Cdk 4 inactivation . ^^^ However , preventing Cyclin D Cdk 4 inactivation by overexpression has a minimal effect on Cyclin E expression and does not interfere with the initial G 1 arrest , while it readily induces the E2F target RnrS in arresting epidermal cells . ^^^ Prolonged Cyclin D Cdk 4 overexpression eventually interferes with maintenance of quiescence in some cells . ^^^ Moreover , in Cdk 4 mutant embryos , some RnrS expression is still induced by Cyclin E overexpression , and endogenous Cyclin E expression as well as cell cycle progression is not affected , except for late aspects of the endoreduplication program . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We previously identified 22 in vivo phosphorylation sites in human p 130 , including three sites selectively targeted by cyclin D Cdk 4 ( 6 ) kinases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In Ang 2 infused rats , vascular DNA synthesis ( by 3H thymidine incorporation ) ; expression of cell cycle proteins cyclin D 1 and cdk 4 , angiotensin 2 type 1 receptors , vascular cell adhesion molecule 1 , and platelet and endothelial cell adhesion molecule ; and nuclear factor kappaB activity were increased . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , IFN alpha inhibited cyclin dependent kinases ( CDK ) , CDK 2 , CDK 3 , CDK 4 , and cyclin E but not cyclin A associated kinase activities . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Myogenic transcription is repressed in myoblasts by serum activated cyclin dependent kinases , such as cdk 2 and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
At the cell cycle level , the HG induced proliferation of MCs was associated with a decrease in cyclin dependent kinase ( CDK ) inhibitor p 21 protein expression accompanied by an increase in CDK 4 and CDK 2 kinase activities . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D and cdk 4 are required for normal development beyond the blastula stage in sea urchin embryos . cdk 4 mRNA and protein are constitutively expressed in sea urchin eggs and throughout embryonic development . ^^^ An increase in cdk 4 kinase activity occurs concomitantly with the increase in cyclin D mRNA . ^^^ In contrast , blocking cyclin D or cdk 4 expression with morpholino antisense oligonucleotides results in normal development of early gastrula stage embryos but abnormal , asymmetric larvae . ^^^ These results suggest that in sea urchins , cyclin D and cdk 4 are required for normal development and perhaps the patterning of the developing embryo , but may not be directly involved in regulating entry into the cell cycle . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The reduction in cell number correlated with a decrease in cyclin D 1 protein expression and a commensurate decrease in Cdk 4 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Recently , we demonstrated that lin 35 Rb also acts as a negative regulator of G ( 1 ) progression and likely is the major target of cyd 1 Cyclin D and cdk 4 CDK4 / 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Our observations were : ( 1 ) a distinct increase in the level of hypophosphorylated retinoblastoma protein ( pRb ) , and a reduction in the level of CDK 4 after treatment with 100 microM of esculetin for 24 h ; ( 2 ) a marked up regulation of p 27 , and a down regulation of cyclin D 1 after treatment with 100 microM esculetin for 24 h . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The positive percentage of cyclin D 1 , CDK 4 , p 16 and Rb was 66 . 7 % , 53 . 3 % , 33 . 3 % , and 36 . 7 % , respectively . ^^^ The overexpression of cyclin D 1 and CDK 4 could be observed frequently in low grade of differentiated cells , especially in marginal cells of the cancer nest . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
JTE 522 inhibited the expressions of COX 2 mRNA , phosphorylated Rb , and CDK 4 proteins , while increased the levels of p 53 , p 21 , cyclin D 1 proteins , and the activity of caspase 3 in RL 95 2 cells . ^^^ CONCLUSION : JTE 522 inhibits cell proliferation and induces apoptosis in RL 95 2 cells , which may be associated with the activation of caspase 3 like proteases , down regulation of the expression of COX 2 mRNA , phosphorylated Rb , and CDK 4 proteins , and up regulation of the expressions of p 53 , p 21 , and cyclin D 1 proteins . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression of the Cdk4 / 6 specific Cdk inhibitor of Cdk 4 p16 ( INK4A ) was associated with increased association of p 27 ( KIP 1 ) with Cdk 2 , concomitant with disruption of D cyclin / Cdk4 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
While expression of the genes for cyclin D 1 , CDK 4 , and E2F1 increased in lung adenocarcinomas relative to normal lung , expression of p 15 ( Ink4b ) , p 16 ( Ink4a ) , p 21 ( Cip 1 ) , p 27 ( Kip 1 ) , p 57 ( Kip 2 ) , and pRb genes decreased in comparison . ^^^ Competitive RT PCR showed that the levels of cyclin D 1 and CDK 4 mRNAs were 2 and 3 fold higher , respectively , in lung adenocarcinomas than in normal lung , while the mRNAs for p 15 ( Ink4b ) , p 16 ( Ink4a ) , p 21 ( Cip 1 ) , p 27 ( Kip 1 ) , and pRb were 3 to 4 fold lower in adenocarcinomas than in normal lung , thus validating the macroarray findings . ^^^ Competitive RT PCR of microdissected lesions also showed that the levels of cyclin D 1 and CDK 4 mRNAs increased significantly , while the mRNAs for p 15 ( Ink4b ) and p 27 ( Kip 1 ) decreased significantly as lung tumorigenesis progressed . ^^^ Immunohistochemical staining for cyclin D 1 and CDK 4 showed staining in > 80 % of nuclei in adenocarcinomas compared with fewer than 20 % of nuclei staining positively in normal lung . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , the protein levels of cyclin D 1 , CDK 4 , PCNA , c myc , and mdm 2 , and cyclin B 1 mRNA level were higher in MNNG+CdCl2 group than control and MNNG group . ^^^ For the purpose , we determined the expression levels of the genes involved in growth regulation , such as p 53 , p 27 , c myc , mdm 2 , cyclins D 1 and B 1 , CDK 4 , and PCNA in the cells treated with Cd for 14 days after MNNG initiation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclin D 1 and CDK 4 causes hypertrophic growth of cardiomyocytes in culture : a possible implication for cardiac hypertrophy . ^^^ In this study , we investigated a role of cyclin D 1 and CDK 4 , a positive regulator of cell cycle , in cultured neonatal rat cardiomyocyte hypertrophy . ^^^ Over expression of cyclin D 1 and CDK 4 using adenovirus gene transfer caused the hypertrophic growth of cardiomyocytes , as evidenced by an increase of the cell size as well as the amount of cellular protein and its rate of synthesis . ^^^ However , the cyclin D1 / CDK4 kinase activity was not up regulated in cells treated by hypertrophic stimuli or in cells over expressing the cyclin D 1 and CDK 4 . ^^^ These results clearly indicated that cyclin D 1 and CDK 4 have a role in hypertrophic growth of cardiomyocytes through a novel mechanism ( s ) which appears not to be related to its activity required for cell cycle progression . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The effect of exposure to 50 Hz , 1 mT magnetic fields ( MF ) on the cell cycle in general , on the DNA synthesis in S phase , and on the G 1 phase regulating proteins Cdk 4 , cyclin D 1 , p16INK4a , and p21CIP1 was investigated in human amniotic fluid cells . ^^^ The protein level of Cdk 4 did not change , but MF induced a decreased expression of cyclin D 1 after 24 h and 30 h exposures . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Transforming growth factor beta ( TGF beta ) induces G ( 1 ) arrest in susceptible cells by multiple mechanisms that inhibit the G ( 1 ) cyclin dependent kinases ( Cdks ) , including Cdk 2 , Cdk 4 , and Cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The effects of exogenous p 16 expression on CDK 4 , Cyclin D 1 and pRb in nasopharyngeal carcinoma cell lines ] . ^^^ OBJECTIVE : To investigate the effect of exogenous p 16 on Cyclin D 1 , CDK 4 and pRb , and to explore the mechanism of the growth suppression of p 16 in nasopharyngeal carcinoma cell lines . ^^^ The expression of p 16 and the effect of exogenous p 16 expression on CDK 4 , Cyclin D 1 and pRb are studied by means of Western Blot . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ectopic overexpression of Jak 3 in 32Dcl3 cells resulted in an acceleration of the G CSF induced differentiation program that was preceded by G ( 1 ) cell cycle arrest , which was associated with the up regulation of the cyclin dependent kinase inhibitor p 27 ( Kip 1 ) and down regulation of Cdk 2 , Cdk 4 , Cdk 6 , and Cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Tumorigenesis is dependent on CDK 4 kinase function , with cyclin D 1 required but not sufficient for this process . ^^^ In facilitating escape from G 1 growth restraints , Ras and CDK 4 alter the composition of cyclin D and cyclin E complexes and promote resistance to growth inhibition by INK 4 cyclin dependent kinase inhibitors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We analyzed the expression of cyclin D 1 and its catalystic partner CDK 4 in colon polyps containing neoplastic foci . ^^^ Our findings suggest that overexpression of cyclin D 1 may be associated with high proliferative activity in adenomatous tissues and that concurrent high expression of cyclin D 1 and CDK 4 may further perturb cell cycle progression and play a pivotal role in colonic carcinogenesis . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : MTT assay was employed to observe the growth inhibition of the VSMCs from rat thoracic aorta cultured in vitro by TNP 470 , and the effect of TNP 470 on the cell cycle and expressions of cyclin D 1 , CDK 4 and p 27 in the VSMCs were examined by flow cytometry . ^^^ After TNP 470 treatment , the expression of cyclin D 1 and CDK 4 in the VSMCs were both significantly decreased ( P < 0 . 05 ) while p 27 underwent contrary changes ( P < 0 . 001 ) . ^^^ CONCLUSION : TNP 470 executes its inhibiting effect on VSMC growth by way of halting the cell cycles , the mechanism of which may involve the expressions of cyclin D 1 , CDK 4 and p27 . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Treatment with monensin for 72 h decreased CDK 4 and cyclin A levels in CA 46 cells , and cdc 2 levels in Molt 4 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , P 21 ( WAF1 / CIP1 ) , GADD 45 and PCNA protein expression were detected by Western blotting and the RT PCR method was applied to study the expression of Cdk 4 . ^^^ RESULTS : Cyclin D 1 , Cdk 4 and PCNA expressions were significantly inhibited , and the expression of P 21 ( WAF1 / CIP1 ) and GADD 45 were significantly induced by tea polyphenols and tea pigments treatments . ^^^ Cyclin D 1 , P 21 ( WAF1 / CIP1 ) , GADD 45 and PCNA protein expression were detected by Western blotting and the RT PCR method was applied to study the expression of Cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Additional in vitro studies demonstrated a G 1 arrest that was preceded by depletion in cyclin D 3 , elevation of p 21 ( WAF 1 ) and p 27 ( KIP 1 ) leading to a loss in activity of G 1 cdks ( cdk 2 , cdk 4 ) , and reduction in pRb phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Silibinin treatment also resulted in 90 and 70 % decrease in CDK 4 and CDK 2 levels , respectively , but did not alter the protein levels of cyclin D 1 and cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of the expression of cell cycle related proteins after the addition of catechin showed that the cyclin dependent kinase ( cdk ) 2 and the cdk 4 proteins were decreased after administration , the expression of cyclin A protein was increased at 24 h after administration , however , the expression of the cyclin D 1 and cyclin E proteins was unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this study , we investigated the mRNA level of several genes involved in cell cycle regulation in alveolar ( ARMS ) and embryonal rhabdomyosarcomas ( ERMS ) . p 21 ( Cip 1 ) , Cyclin D 1 , Cyclin D 2 , Cyclin D 3 , CDK 2 , and CDK 4 were evaluated by RT PCR . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Deregulation of D type cyclin dependent kinases ( CDK 4 and 6 ) is widely observed in various human cancers , illustrating their importance in cell cycle control . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Transfection of a mutant cyclin D 1 ( cyclin D 1 KE ) that was unable to bind CDK 4 and was reported to transactivate ER in the presence of ICI 182780 , could not stimulate proliferation in ICI 182780 treated cells . ^^^ Furthermore , transient transfection of T47D cells using cyclin D 1 together with a catalytic inactive mutant of CDK 4 ( CDK 4 DN ) indicated that the observed effect is due to binding to CDK inhibitors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
FISH analysis was performed on the oncogene cyclin D 1 and IHC analysis on the proteins cyclin D 1 , p 53 , p 16 , cdk 4 , bcl 2 , mdm 2 and rb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In differentiated F 9 cells , the activity of cyclin Cdk complexes , comprising Cdk 4 and Cdk 2 kinases and cyclins A and E , was significantly decreased . ^^^ A decrease of Cdk 4 kinase activity correlates with a drop of the cyclin D 1 content . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D type cyclins bind to and activate the cyclin dependent kinases Cdk 4 and Cdk 6 , which in turn phosphorylate their downstream target , the retinoblastoma protein Rb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Under these conditions T cells expressed CD 25 and CD 69 and progressed through the first 12 hr of G0 / G1 phase but did not express CD 71 , cyclin D 3 , cdk 4 , begin DNA synthesis , or differentiate into cytotoxic effector cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Downregulation of the kinase activities is mediated by induction of cyclin dependent kinase ( CDK ) inhibitor p 15 ( Ink4b ) which blocks CDK 4 and CDK 6 kinases and leads to binding of p 27 ( Kip 1 ) to CDK 2 cyclin E complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Investigations of G1 / S regulatory proteins by Western blot analyses showed an upregulation of p 27 , and decreased expression levels of cyclin E and CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blotting method was employed in the examination of the expression of cyclin D 1 , E and that of cyclin dependent kinase ( CDK ) 2 and CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
AGC 10 also caused large reductions in the mRNA levels of cyclin D 2 and cdk 4 , both critical for progression through G 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
H ( 2 ) O ( 2 ) ( 100 microM ) blocked serum stimulated cyclin dependent kinase 2 ( CDK 2 ) activity , but not CDK 4 activity , suggesting that cell cycle arrest occurred in part by inhibiting CDK 2 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Silibinin treated cells showed up to 2 . 4 and 3 . 6 fold increases in Cip1 / p21 and Kip1 / p27 levels , respectively , and a decrease in CDK 2 ( 80 % ) , CDK 4 ( 98 % ) , and cyclin D 1 ( 60 % ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this work , we investigated whether the kinase activity of the CdK 4 and 6 cyclin complexes can be modulated by CdKI p 16 ( Ink 4a ) , by changes in the protein level of CdKs and cyclins , or by changes in kinase activity of these CdKs not directly involving CdKIs . ^^^ This CdK 2 mediated effect should be considered in addition to the inhibition of cyclin D CdK 4 and 6 complexes by CdKI p 21 ( Waf 1 ) . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Both cdk 4 and cdk 6 were notably dissociated from cyclin D cofactors , while cyclin E cdk 2 complexes remained coupled in TGFbeta 1 treated cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blotting assay was carried out to detect the expression of cyclin D 1 , CDK 4 , and P 21 ( WAF1 / CIP1 ) on whole liver extract . ^^^ It was also found that the expression of P 21 ( WAF1 / CIP1 ) was significantly induced and the expression of cyclin D 1 and CDK 4 was significantly inhibited in tea treated groups . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , VES reduces cdk 4 kinase activity , Rb phosphorylation , and cyclin E mRNA expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
When we examined the effects of this drug on SNU C 1 cells , monensin decreased the levels of CDK 2 , CDK 4 , CDK 6 , cyclin D 1 and cyclin A proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis revealed that oxLDL stimulated cell proliferation was associated with significant increases in the expression of proteins that regulate entry into and progression through the cell cycle [ cell division cycle 2 , cyclin dependent kinase ( cdk ) 2 , cdk 4 , cyclin B 1 , cyclin D 1 , and PCNA ] . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cyclin D dependent kinase Cdk 4 promotes progression through the G ( 1 ) phase of the cell cycle and is deregulated in many human tumors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analyses in SK Hep 1 cells revealed a deficient cyclin D induction in IFN gamma treated cells , resulting in reduced activity of CDK 4 and CDK 2 kinases and pRB hypophosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
There were no significant changes in cyclin D 1 or CDK 4 expression induced by ATRA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The INK 4 family of cyclin dependent kinase ( CDK ) inhibitors negatively regulates cyclin D dependent CDK 4 and CDK 6 and thereby retains the growth suppressive function of Rb family proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As shown by immunoblot analysis , EGCG treatment of LNCaP and DU 145 cells resulted in significant dose and time dependent ( 1 ) upregulation of the protein expression of WAF1 / p21 , KIP1 / p27 , INK4a / p16 , and INK4c / p18 , ( 2 ) down modulation of the protein expression of cyclin D 1 , cyclin E , cdk 2 , cdk 4 , and cdk 6 , but not of cyclin D 2 , ( 3 ) increase in the binding of cyclin D 1 toward WAF1 / p21 and KIP1 / p27 , and ( 4 ) decrease in the binding of cyclin E toward cdk 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunocytochemical colocalization of cyclin D and cdk 4 showed that , before the initial treatment began , patients were distributed disproportionately among treatment subgroups in regards to the initial expression of these markers . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Our data suggest that Hsc 70 promotes stabilization of newly synthesized cyclin D 1 , thereby increasing its availability for assembly with CDK 4 . ^^^ In addition , our data demonstrate that Hsc 70 remains bound to cyclin D 1 following its assembly with CDK 4 and Cip / Kip proteins , where it ensures the formation of a catalytically active complex . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Virtually all mammalian cells express two seemingly redundant cyclin D dependent kinases ( Cdk 4 and Cdk 6 ) and three partner cyclins ( D 1 , D 2 and D 3 ) essential for the G ( 1 ) S transition , with predominant expression of Cdk 4 and D 1 in mesenchymal cells and Cdk 6 and D 3 in hematopoietic cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The protein levels of cyclins D 1 , E , A , and H , and of cyclin dependent kinase 1 ( Cdk 1 ) , Cdk 2 , Cdk 4 , Cdk 6 , and Cdk 7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot . ^^^ Protein levels and kinase activities of cyclin D 1 , Cdk 4 , cyclin E , cyclin A , and Wee 1 were significantly elevated in HCC compared with surrounding cirrhotic tissues . ^^^ The enhanced cyclin D 1 related kinase activity in HCC was accompanied by the up regulation of Cdk 4 activity , but not Cdk 6 activity . ^^^ In addition , the protein levels and kinase activities of cyclin D 1 , Cdk 4 , and cyclin E were higher in poorly differentiated HCC and advanced HCC . ^^^ In conclusion , the increases of cyclin D 1 , Cdk 4 , cyclin E , cyclin A , and Wee 1 play an important role in the development of HCC from cirrhosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In order to understand the mechanism ( s ) of tumor promotion by MY and MG , we have studied the levels of PCNA , a marker of cell proliferation and cell cycle regulatory proteins , cyclin D 1 , and its associated kinase , cdk 4 , cyclin B 1 , and associated kinase , cdc 2 . ^^^ Western and Northern blot hybridization showed an increased expression of both cyclin D 1 and its associated kinase cdk 4 , and cyclin B 1 and its associated kinase cdc 2 , in livers of rats administered MY and MG after administration of DEN as compared to untreated or DEN controls . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The protein levels of p 53 , p 16 , cyclin D 1 and CDK 4 were assayed by immunocytochemistry . ^^^ RESULTS : After tachyplesin treatment , the cell cycle arrested at G0 / G1 phase , the protein levels of mutant p 53 , cyclin D 1 and CDK 4 and the mRNA level of c myc gene were decreased , whereas the levels of p 16 protein and p 21 ( WAF1 / CIP1 ) mRNA increased . ^^^ CONCLUSION : Tachyplesin might arrest the cell at G0 / G1 phase by upregulating the levels of p 16 protein and p 21 ( WAF1 / CIP1 ) mRNA and downregulating the levels of mutant p 53 , cyclin D 1 and CDK 4 proteins and c myc mRNA , and induce the differentiation of human hepatocacinoma cells . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Compared to normal human mucosa , epithelia migrating to cover 2 or 3 day old wounds made either in vivo or in an organotypic cell culture all showed loss of the proliferation marker Ki 67 and cyclins D ( 1 ) and A , and reduced expression of cyclins D ( 3 ) and E , the cyclin D dependent kinase 4 ( CDK 4 ) , the MCM 7 component of DNA replication origin complexes and the retinoblastoma protein pRb . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Upregulation of cyclin D 2 and D 3 in activated B CLL cells was inhibited while the expression of cdk 2 , cdk 4 , and cyclin E remained unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Reductions in cyclin dependent kinase ( CDK ) 2 ( 82 % ) and CDK 4 ( 77 % ) kinase activity in ER carcinomas were likely to account for the observed effects on retinoblastoma and E2F 1 . ^^^ On the other hand , regulation of CDK 4 kinase activity by ER was likely attributable to effects on cyclin D 1 as well as increased binding of P 16 and P 19 to CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In these cells E 2 causes the translocation of cyclin D1 / cyclin dependent kinase 4 ( CDK 4 ) from the cytoplasm into the nucleus with the consequent phosphorylation of the retinoblastoma protein . ^^^ This CDK 4 activity was due to complexes of cyclin D2 / CDK4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The increase of Cdk 4 activity in SOD 1 ( G37R ) mice was associated with an increase in nuclear Cdk 4 , cyclin D 1 , its coactivator , and with the abnormal phosphorylation of the retinoblastoma ( Rb ) protein at Cdk phosphorylation sites . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Quantitative reverse transcription polymerase chain reaction verified mRNA changes in this group , which included gadd45a , c myc , cyclin D 1 and cdk 4 , pcna , cyclin G , Rb , and E2F5 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cpd 5 decreased the levels of cyclin D 1 , Cdk 4 , p 16 , p 21 and cyclin B 1 . ^^^ By contrast , VK 3 only decreased the level of cyclin D 1 , but had no effect on the levels of Cdk 4 , p 16 or p 21 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RESULTS : By flow cytometry , apoptosis was observed in all cell lines overexpressing cdk 4 or cyclin D 1 . ^^^ Immunofluorescence revealed that cells overexpressing cdk 4 or cyclin D 1 exhibited nuclear features characteristic of apoptosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
When we examined the effects of this drug on ACHN cells , trichostatin decreased the levels of CDK 4 , CDK 6 , cyclin D 1 and cyclin A proteins . p 27 protein was increased by trichostatin . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although the majority of target genes studied [ class 1 : B 23 ( NPM 1 ) , CAD , CDK 4 , cyclin D 2 , ID 2 , LDH A , MNT , PTMa , ODC , NM23B , nucleolin , prohibitin , SHMT 1 , and SHMT 2 ] demonstrate significant sequence conservation of the E boxes and flanking regions , several genes ( cyclin B 1 , JPO 1 , and PRDX 3 ) belong to a second class ( class 2 ) that does not display sequence conservation at and around the site of c Myc binding . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of G ( 1 ) phase regulatory proteins demonstrated that the protein levels of cyclin dependent kinase 2 ( Cdk 2 ) , Cdk 4 , Cyclin E and Cyclin D 3 were decreased after treatment with SCK 6 but not those of Cdk 6 , Cyclin D 1 and D 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclic AMP dependent phosphorylation of cyclin D 3 bound CDK 4 determines the passage through the cell cycle restriction point in thyroid epithelial cells . ^^^ It appeared in response to forskolin and was bound to both cyclin D 3 and p 27 , presumably reflecting the activating Thr 172 phosphorylation of CDK 4 . ^^^ Upon forskolin withdrawal or after cycloheximide addition , this CDK 4 phosphoform unexpectedly persisted in p 27 complexes devoid of cyclin D 3 but it disappeared from the more labile cyclin D 3 complexes . ^^^ These data demonstrate that the assembly of the cyclin D 3 CDK4 p 27 holoenzyme and the subsequent phosphorylation and activation of CDK 4 depend on distinct cAMP actions . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The induction of Cdk 4 expression and activity is also markedly attenuated , which likely contributes to the inhibition of cyclin E expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Increased levels of cdk 4 and cyclin D 1 proteins were found in the colonic epithelium of progastrin overexpressing mice relative to wild type animals after gamma radiation . ^^^ Persistently elevated cdk 4 and cyclin D 1 in progastrin overexpressing mice accounts for the capacity of colon cells to continue with the cell cycle after DNA damage . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Results of in vitro testing demonstrate that flavopiridol has several relevant clinical characteristics such as its ability to : 1 . inhibit cell growth ; 2 . inhibit cell migration ; 3 . decrease expression of cyclin D 1 , CDK 4 and p 21 ; 4 . induce apoptosis in cells with high levels of p 27 expression ; and 5 . decrease the expression of the anti apoptotic protein Bcl 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We also show that cells expressing a mutant of cyclin D 1 that can not bind to cdk 4 are also more sensitive to fenretinide . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The aim of this study was to analyze the clinicopathological features and immunohistochemical expression of p 53 , MDM 2 , CDK 4 , PCNA and Ki 67 proteins in 25 head and neck osteosarcomas registered in a single institution . ^^^ The immunohistochemical analysis displayed positivity in 52 % of the cases for p 53 , 24 % for MDM 2 , 84 % for CDK 4 , 92 % for PCNA and 88 % for Ki 67 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To improve understanding of the role of this pathway in spermatogenesis , and its subversion in TGCTs , we examined immunohistochemical expression patterns of CDK 4 , p16INK4a , p15INK4b , and pRB , and established an in situ assay for cyclin D mediated phosphorylation of serine 795 , a phosphorylation event critical for neutralization of pRB ' s growth restraining ability . pRB was expressed throughout adult spermatogenesis and was detectable in teratomas , but was absent or grossly reduced in carcinoma in situ ( CIS ) and most seminomas and embryonal carcinomas . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , degradation of the AhR in HepG 2 liver cancer cells resulted in decreased G0 / G1 > S phase progression , and this was accompanied by decreased expression of cyclin D 1 , cyclin E , cyclin dependent kinase 2 ( cdk 2 ) , and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We observed high levels of p27kip1 , cyclin D 2 , cyclin E , cdk 2 , and cdk 4 expression in freshly isolated B CLL cells . ^^^ Despite high levels of cyclins and cdks , little cdk 2 or cdk 4 activity was observed with p27kip1 in complex with cyclinD2 / cdk4 and cyclin E / cdk2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Monensin decreased the levels of CDK 2 , CDK 6 , cdc 2 , cyclin A , cyclin B 1 , cyclin D 1 and cyclin E proteins but did not alter CDK 4 protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the present study , expression of cyclins ( D 1 , E , A , and B 1 ) , cyclin dependent kinases ( cdk 2 , cdk 4 , and cdc 2 ) , and tumor suppressor gene products ( p 53 , p 21 , and p 27 ) were systematically examined by immunohistochemistry in 82 cases of endometrial carcinoma and 20 normal endometria . ^^^ Positive staining for cyclin D 1 , cyclin E , cyclin A , cyclin B 1 , cdk 2 , cdk 4 , cdc 2 , p 53 , p 21 , and p 27 was observed in 63 % , 66 % , 31 % , 32 % , 51 % , 77 % , 71 % , 43 % , 35 % , and 60 % of the 82 carcinomas , respectively . ^^^ Among these factors , positive staining for cyclin D 1 , cdk 4 , and p 53 was significantly frequent in advanced stage tumors , and that for cyclin D 1 , cyclin A , cdk 4 , p 21 , and p 53 was more frequent in higher grade tumors . ^^^ High correlation was found between cyclin A and p 53 expression , between cyclin D 1 and cdk 4 expression , between cdk 4 and Ki 67 expression , and between p 21 and Ki 67 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Levels of cyclin D 1 , cyclin E , cyclin dependent kinase ( CDK ) 2 and CDK 4 were reduced in carcinomas from corticosterone treated rats ; whereas , levels of cyclin dependent kinase inhibitors ( CKI ) Kip1 / p27 and Cip1 / p21 were elevated . ^^^ Binding of these CKIs to both the cyclin D 1 CDK 4 complex and the cyclin E CDK 2 complex were increased and the kinase activities of these complexes were reduced with increasing dietary corticosterone . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Genetic characterization was performed using cytogenetics , fluorescence in situ hybridization , flow cytometry , and molecular techniques for analysis of the genes implicated in cell cycle control , amplification of MDM 2 , CDK 4 , and Cyclin D 1 , and mutations in the p 53 gene . ch 2879 cells were subcultured for more than 80 passages . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blotting analysis revealed that the protein levels of cyclin A , cyclin E , and cyclin dependent kinase ( CDK ) 2 but not cyclin D 1 and CDK 4 decreased after progesterone treatment , but those of CDK inhibitory proteins , p 21 and p 27 , increased . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Liver weight , protein and DNA contents , DNA synthesis ( 5 ' bromodeoxyuridine ( BrdU ) incorporation ) and cellular levels of Cyclin E , CDK 2 , CDK 4 and proliferating cell nuclear antigen ( PCNA ) were assessed before and 24 , 48 , 72 and 168 h after PBL . ^^^ RESULTS : Before surgery , higher levels of cyclin E , CDK 2 , CDK 4 and PCNA as well as BrdU incorporation were found in the liver of retrorsine treated rats than in untreated rats . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Overexpression of cyclin D 1 , the regulatory subunit of cyclin dependent kinases ( cdk 4 and cdk 6 ) involved in cell cycle control , has often been found in breast cancer and other types of human cancer . ^^^ Increased expression , or stability , of cyclin D 1 molecules may cause sufficient cdk 4 activation to produce retinoblastoma protein phosphorylation independently of mitogenic signals ; this results in commitment of cells to the G 1 phase at mitosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In our study , we screened HCCs resulting from HCV infection ( 51 cases ) , HBV infection ( 26 cases ) or excess alcohol intake ( 23 cases ) for alterations in genes involved in the RB 1 pathway ( p 16 ( INK4a ) , p 15 ( INK4b ) , RB 1 , CDK 4 and cyclin D 1 ) , the p 53 pathway ( p 53 , p 14 ( ARF ) and MDM 2 ) and the Wnt pathway ( beta catenin , APC ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
No changes were observed in the expression levels of the G 1 regulatory molecules cyclin D 1 and cdk 4 , but cell cycle arrest and apoptosis induction was accompanied by accumulation of the cdk inhibitor p 21 in both cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The three human D type cyclins , cyclin D 1 , D 2 and D 3 share the ability to bind to and activate cdk 4 and 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The biological characteristics were studied by cell growth curve , colony formation analysis , and the determination of telomerase activity and protein expression of Cyclin A , p 21 , and CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The restored ZD : AZ forestomach epithelium displayed strong expression of Bax , a proapoptotic protein , and weak staining of cyclin D 1 and its catalytic partner Cdk 4 , key regulatory proteins controlling G ( 1 ) to S progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Arsenic increased expression of the P 21 protein and decreased levels of cyclin A , cyclin B 1 and cyclin D 1 , but expression of CDK 2 , CDK 4 , CDK 6 , and cyclin E were not affected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Sperm counts , sperm motility , and sperm silver staining were used to test the antispermatogenic effect of triptonide ; the study of morphology was learned from paraffin sections of testis and visceras of triptonide treated rats ; protamine was abstracted from testis by electrophoresis ; using antisense mRNA of cyclin D 1 and Cdk 4 as prodes , we examined the expression of cyclin D 1 and Cdk 4 through hybridization in situ . ^^^ By using antisense mRNA of cyclin D 1 and Cdk 4 as prodes , we detected that the expression of the genes was notably increased in spermatids . ^^^ CONCLUSIONS : The results suggest the antispermatogenic effect of triptonide is very well and it mainly plays its role on spermatids by increasing the expression of cyclin D 1 and Cdk 4 , meanwhile , decreasing the biosynthesis of protamine . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
With increased Cdc 37 expression , molecular analysis of Cdc 37 client pathways demonstrates enhanced Raf 1 activity , greater Cdk 4 levels , and reduced expression of the cyclin dependent kinase inhibitor p16 / CDKN2 . ^^^ Induction of Cdk 4 activity using cyclin D 1 overexpression , however , was sufficient to promote proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
At least four of these so called cyclin dependent kinases , namely Cdk 4 , Cdk 6 , Cdk 2 and Cdk 1 , have specific roles at particular stages of the cell cycle , including passage through the various cell cycle transitions and the response to specific checkpoints . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Human colon cancer cell lines SW 480 and HCT 116 were transfected with Stat 3 antisense oligonucleotide mediated by liposome , MTT assay was used to measure the proliferation , flow cytometry was applied to analyze the cell cycle , and the expressions of Stat 3 , phosphorylation specific Stat 3 ( tyrosine 705 ) , Cyclin D 1 , Cyclin E , CDK 2 , CDK 4 , CDK 6 , p 21 and p 27 were measured by western blot . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The inactivation of p 27 ( kip 1 ) and the consequent disruption of normal colonic cell maturation in the mucosa were associated with modestly elevated c myc , cdk 4 , and cyclin D 1 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Coinciding with the arrest is a reduction in the activity of CDK 4 , due to either the observed PBOX 21 induced downregulation in CDK 4 expression , or a reduction in complex formation between cyclin D ( 3 ) CDK 4 leading to a decrease in the levels of active cyclin D ( 3 ) CDK 4 complexes with kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 plays an important role in the regulation of G 1 progression of the somatic cell cycle by functioning as a regulatory subunit of cdk 4 and 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
No direct interaction of Id 2 with cyclin D 1 or its binding partner cdk 4 was detected in mammalian two hybrid assays . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cells were arrested in G2 / M phase after 15 deoxy PGJ 2 treatment with concomitant increase in the expression of G2 / M phase regulatory protein cyclin B 1 but decrease in the expression of cdk 2 , cdk 4 , cyclin A , cyclin D 1 , cyclin E , and cdc25C . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Defective cell cycle control in the absence of Mnt is linked to upregulation of Cdk 4 and cyclin E and the Cdk 4 gene appears to be a direct target of Mnt Myc antagonism . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cell cycle associated proteins such as cyclin D 1 , cyclin E , CDK 2 , and CDK 4 , and kinase activities associated with CDK 2 and CDK 4 were increased in aged MASMC . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The data show that 1 ) . mouse oocytes contain significant amounts of all studied regulators ; 2 ) . their amounts and localization undergo dramatic changes as the oocytes grow , meiotically mature , and transit into embryogenesis ; and 3 ) . some regulators ( CDK 4 , CDK 6 , cyclin D 2 , and p 27 ) appear in unusual , most likely posttranslationally modified , forms . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here , we demonstrate that in platelet derived growth factor ( PDGF ) stimulated mesangial cells , PTX causes G 1 arrest by down regulation of cyclin D 1 expression , which subsequently attenuates Cdk 4 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To date only one class of substrates have been identified for cyclinD CDK 4 and CDK 6 complexes , those belonging to pRb family of proteins , whereas the list of cyclin E CDK 2 substrates continues to lengthen . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
P27Kip1 and p21Cip1 are not required for the formation of active D cyclin cdk 4 complexes . ^^^ Our studies address questions pertaining to the regulation of D cyclin cdk 4 activity , and the following results were obtained . ^^^ Conditions that increased the abundance of the D cyclins also increased the abundance of enzymatically active D cyclin cdk 4 complexes in mouse embryo fibroblasts ( MEFs ) lacking both p 27 ( Kip 1 ) and p 21 ( Cip 1 ) ( p27 / p21 ( / ) ) . ^^^ However , as determined by treatment of wild type MEFs with MG 132 , maximal accumulation of D cyclin cdk 4 complexes required p 27 ( Kip 1 ) and p 21 ( Cip 1 ) and coincided with the formation of inactive D cyclin cdk 4 p27 ( Kip 1 ) or p 21 ( Cip 1 ) complexes . p 27 ( Kip 1 ) or p 21 ( Cip 1 ) also increased the abundance of D cyclin cdk 4 complexes and reduced amounts of cdk 4 activity when ectopically expressed in p27 / p21 ( / ) MEFs . ^^^ We conclude that ( 1 ) D cyclin cdk 4 complexes are formed and become active in the absence of p 27 ( Kip 1 ) and p 21 ( Cip 1 ) and ( 2 ) p 27 ( Kip 1 ) and p 21 ( Cip 1 ) maximize the accumulation but inhibit the activity of D cyclin cdk 4 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
By immunohistochemical analysis , cyclin D 1 , Cdk 4 , and phospho Rb nuclear protein expression was 5 . 7 , 3 . 9 , and 2 . 3 fold higher , respectively , in carcinomas than in normal mammary gland , whereas the expression of cyclin D 2 , cyclin D 3 , and Cdk 6 was similar . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This effect was accompanied by the decreased expression of G ( 1 ) associated proteins including cyclin D 1 , CDK 4 , and Rb phosphorylation at Ser 780 , Ser 795 , and Ser807 / 811 , whereas expression of CDK 6 and beta actin was not affected by LY 294002 . ^^^ The mTOR inhibitor rapamycin has similar inhibitory effects on G ( 1 ) cell cycle progression and expression of cyclin D 1 , CDK 4 , and Rb phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cell cycle promoters , cyclin D 1 , cyclin E , Cdk 2 , and Cdk 4 was assessed by immunoblotting . ^^^ This was associated with increased protein content of cyclin D 1 and Cdk 4 and decreased activation of p 21 ( cip 1 ) and p 27 ( kip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Representative large cell genes ( E2F3 , MYBL 2 , HDAC 2 , CDK 4 , PCNA ) are expressed in the nucleus and are associated with cell cycle and proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The levels of cyclin E and CDK 2 were increased in HOMFs after 100 microg / ml of AESR treatment , but the levels of cyclin D , CDK 4 , and CDK 6 were unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here , the nuclear translocation of these complexes strictly correlated in individual cells with the enhanced presence of nuclear p 27 . p 27 , like cyclin D 3 , supported the TSH stimulated pRb kinase activity of the CDK 4 complex and , as demonstrated using the high resolution power of the two dimensional ( 2D ) gel electrophoresis , the phosphorylation of CDK 4 , presumably by the nuclear CDK activating kinase . ^^^ In the presence of TSH , transforming growth factor beta ( TGFbeta ) did not affect the assembly of cyclin D 3 CDK4 , but it strongly inhibited the pRb kinase activity associated with both cyclin D 3 and p 27 , not only by preventing the nuclear import of cyclin D 3 CDK4 and its binding to p 27 , but also by inhibiting CDK 4 phosphorylation within residual p 27 bound cyclin D 3 CDK4 complexes . ^^^ This study suggests a crucial positive role of p 27 in the TSH stimulated nuclear import , phosphorylation , and catalytic activity of cyclin D 3 bound CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
S / K deprivation induced the expression of cell cycle proteins such as cyclin E , cyclin A , cdk 2 , cdk 4 and E2F 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have cloned and expressed cyclin D1b , and find that it retains the ability to bind to and activate CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In mechanistic studies related its effect on cell cycle progression , silibinin treatment resulted in an upregulation of Kip1 / p27 and Cip1 / p21 protein as well as mRNA levels , and decreased CDK 2 , CDK 4 , cyclin E and cyclin D 1 protein levels together with an inhibition in CDK 2 and CDK 4 kinase activities . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The mRNA of cyclin D 1 and CDK 4 were examined by RT PCR . ^^^ CONCLUSION : The Erk signal transduction pathway plays an important role in regulating the proliferation and cell cycle of rat hepatic stellate cells stimulated by acetaldehyde , which may be partly related to its regulative effect on the expression of cyclin D 1 gene and CDK 4 gene . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The interruption of cell cycle progression in the presence of thialysine was accompanied by a significant decline in the protein level of cdk 4 , cdk 6 , cdc 2 , cyclin A , cyclin B 1 , and cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Scattered neurons contained elevated levels of cyclin D 1 , CDK 2 and , to a lesser extent , CDK 4 , but little or no cyclin A or E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , in TNFR 1 / mice , which exhibit exaggerated acetaminophen hepatotoxicity , hepatocyte proliferation , and expression of cyclin D 1 and cyclin A , as well as the cyclin dependent kinases , Cdk 4 and Cdk 2 , were reduced . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of cyclin E renders cyclin D CDK 4 dispensable for inactivation of the retinoblastoma tumor suppressor protein , activation of E2F , and G 1 S phase progression . ^^^ The phosphatidylinositol 3 OH kinase inhibitor LY 294002 has been shown to block cyclin D 1 accumulation , CDK 4 activity and , thus , G 1 progression in alpha thrombin stimulated IIC 9 cells ( Chinese hamster embryonic fibroblasts ) . ^^^ Our previous results show that expression of cyclin E rescues S phase progression in alpha thrombin stimulated IIC 9 cells treated with LY 294002 , arguing that cyclin E renders CDK 4 activity dispensable for G 1 progression . ^^^ In this work we investigate the ability of alpha thrombin induced CDK 2 cyclin E activity to inactivate pRb in the absence of prior CDK 4 cyclin D 1 activity . ^^^ We report that in the absence of CDK 4 cyclin D 1 activity , CDK 2 cyclin E phosphorylates pRb in vivo on at least one residue and abolishes pRb binding to E2F response elements . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In a previous study , we reported that overexpression of cyclin dependent kinase 4 ( CDK 4 ) in mouse epidermis results in epidermal hyperplasia , hypertrophy and severe dermal fibrosis . ^^^ These results suggest that expression of cyclin D 1 upon ras activation synergizes with CDK 4 overexpression . ^^^ However , cyclin D 1 transgenic mice and double transgenic mice for cyclin D 1 and CDK 4 did not show increased malignant progression in comparison to CDK 4 transgenic mice . ^^^ These results indicate that , contrary to the general assumption , the catalytic subunit , CDK 4 , has higher oncogenic activity than cyclin D 1 , revealing a potential use of CDK 4 as therapeutic target . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression of the cell cycle regulatory proteins ( pRb , cyclin D 1 , p16INK4A and cdk 4 ) in human endometrial cancer : correlation with clinicopathological features . ^^^ Currently , we assessed the expression of cell cycle regulatory proteins ( pRb , cyclin D 1 , p 16 ( INK4A ) and cdk 4 ) in 48 sporadic endometrial cancers , and investigated these tumors for a possible relationship between aberrant protein staining and clinicopathological variables of cancer and RB LOH . ^^^ There was abnormal pRb , cyclin D 1 , p 16 ( INK4A ) and cdk 4 immunoreactivity in 2 % , 50 % , 6 % and 25 % of cases , respectively . ^^^ However , there was significant correlation neither between the cell cycle regulators nor between the frequency of pRb , p 16 ( INK4A ) and cyclin D 1 abnormalities and clinicopathological variables of cancer , but a significant correlation did exist between cdk 4 staining and the clinical stage of disease ( P < 0 . 05 , Fisher ' s exact test ) . ^^^ As a conclusion , derailments of the Rb pathway components , cyclin D 1 and cdk 4 in particular , seems to participate in the endometrial cancer development in humans . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
SFN induced signals that inhibited the activity of cyclin dependent kinase cdk 4 with an up stream induction of cdk inhibitor p21WAF 1 / Cip 1 , and reduced cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ectopic c Fos resulted in increased expression of cyclins A and E protein levels , and premature activation of cyclin A , cyclin E , and cyclin dependent kinase ( CDK ) 2 associated kinase activities , although cyclin D levels and CDK 4 activity were not affected significantly in these cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Identification of a conserved sequence motif that promotes Cdc 37 and cyclin D 1 binding to Cdk 4 . ^^^ However , in contrast to wild type Cdk 4 , Cdk 4 ( G15A ) , and Cdk 4 ( G18A ) had greatly reduced binding of cyclin D 1 , Cdc 37 , and Hsp 90 . ^^^ Importantly , overexpression of Cdc 37 not only stimulated cyclin D 1 binding to wild type Cdk 4 but also restored its binding to Cdk 4 ( G15A ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Over expression of cyclin D 1 regulates Cdk 4 protein synthesis . ^^^ Increased Cdk 4 expression occurs coincident with over expression of cyclin D 1 in many human tumours and tumourigenic mouse models . ^^^ Here , we investigate both in vivo and in vitro the mechanism by which Cdk 4 expression is regulated in the context of cyclin D 1 over expression . ^^^ Cdk 4 mRNA levels in cyclin D 1 over expressing tissue and cultured cells were unchanged compared with controls . ^^^ In contrast , Cdk 4 protein levels were increased in cyclin D 1 over expressing tissue and cells versus their respective controls . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : We examined expression patterns of cyclin D 1 ; cyclin E ; cyclin A ; cyclin B 1 ; cyclin dependent kinase ( CDK ) 2 ; CDK 4 ; such CDK inhibitors as p21WAF1 / CIP1 ( p 21 ) , p27kip1 ( p 27 ) , and p57kip2 ( p 57 ) ; and Wilms ' tumor protein 1 ( WT 1 ) in 12 renal biopsy specimens with the cellular lesion of FSGS and 6 renal biopsy specimens with no detectable abnormalities by immunohistochemistry and immunoelectron microscopy . ^^^ RESULTS : In controls , immunostaining for cyclin A , cyclin B 1 , CDK 2 , CDK 4 , and p 21 was almost negligible , but positive signals for cyclin D 1 , cyclin E , p 27 , and p 57 were observed in glomerular epithelial cells ( GECs ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
A heterozygous mutation in the gene encoding the cell cycle regulator , cyclin D kinase 4 ( Cdk 4 ) , affected expression of many genes involved in cell growth and proliferation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
It can be concluded that although CYC 202 can act as a CDK 2 inhibitor , it also has the potential to inhibit CDK 4 and CDK 1 activities in cancer cells through the down regulation of the corresponding cyclin partners . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here we show that in WI 38 human diploid fibroblasts KN 93 reversibly arrested cells in late G ( 1 ) prior to detectable cyclin dependent kinase 4 ( cdk 4 ) activation . ^^^ Additional examination of cdk 4 complexes by gel filtration analysis demonstrated that , in late G ( 1 ) , cyclin D 1 containing complexes migrated toward lower molecular weight ( M ( r ) ) fractions and this altered migration was accompanied by the appearance of two peaks of cdk 4 activity , at 150 200 and 70 kDa , respectively . ^^^ KN 93 prevented both the activation of cdk 4 , and this shift in cyclin D 1 migration and overexpression of cyclin D1 / cdk4 overcame the KN 93 arrest . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The most potent compound , actein , decreased the level of cyclin D 1 , cdk 4 and the hyperphosphorylated form of the pRb protein and increased the level of p21cip1 in MCF 7 cells , changes that may contribute to the arrest in G 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Instead , oxLDL inhibited the translocation of cell cycle proteins cell division cycle ( Cdc ) 2 , cyclin dependent kinase ( Cdk ) 2 , Cdk 4 , Cyclin A , Cyclin B 1 , Cyclin D 1 , and proliferative cell nuclear antigen ( PCNA ) into the nucleus , as compared with separate treatments with serum alone . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Of the regulatory molecules , cyclin D 1 , CDK 2 and CDK 4 were expressed in both CAR and ICAR cells derived from both nonpregnant , and AI cows on days 30 and 60 of gestation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Our data show that succinyl acetone induced heme deficiency increases the protein levels of the tumor suppressor gene product p 53 and CDK inhibitor p 21 , and decreases the protein levels of Cdk 4 , Cdc 2 , and cyclin D 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
AGN 194204 dependent suppression of MIA PaCa 2 cell proliferation is associated with reduced cyclin E and cyclin dependent kinase 6 ( cdk 6 ) level , but cyclin D 1 , cdk 2 and cdk 4 content is not altered . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Combination 1 , 25 ( OH ) ( 2 ) D ( 3 ) and bryostatin 1 treatment , resulted in decreased expression of the cyclin dependent kinases Cdk 2 , Cdk 1 , and Cdk 4 , of cyclins E and D 3 , and of the retinoblastoma binding protein ( RBBP ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , Ganfujian granule had a marked inhibitory effect on high expression of cyclin dependent kinase ( CDK 4 ) during the whole process of hepatocarcinogenesis and cyclin D 1 at week 16 and the number of proliferating cell nuclear antigen ( PCNA ) positive cells in different stages of hepatocarcinogenesis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Expression patterns of regulatory proteins such as p 53 , cyclin D 1 , p 16 , Cdk 4 , p 21 , Rb , bcl 2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Ectopic expression of dMyc induces expression of Cyclin E , Cyclin D , and Cdk 4 , which can inhibit Rbf and promote G ( 1 ) S progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This was associated with enhanced p 53 dephosphorylation and p 21 ( Cip1 / Waf1 ) expression , which coincided with decreased Cdk 2 , Cdk 4 , and cyclin E expression , compared with synchronized G 1 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The mTOR inhibitor rapamycin had similar inhibitory effects on G ( 1 ) cell cycle progression and on the expression of cyclin D 1 , CDK 4 , CDC25A , and retinoblastoma phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Among the G 1 phase cell cycle related proteins , the levels of cyclin dependent kinase ( CDK ) 6 and cyclin D 1 were reduced by saucernetin 7 , whereas the steady state levels of CDK 2 , CDK 4 , cyclin D 2 , cyclin D 3 and cyclin E were unaffected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We further showed that Tat interacted with a number of cell cycle related proteins including cyclin A , cyclin B , cyclin D 3 , Cdk 2 , Cdk 4 , Cdk1 / Cdc2 , cdc 6 , p 27 , p 53 , p 63 , hdlg , and PCNA . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In rasREF cells treated with DE for 72 h in suspension culture ( a ) , the levels of cyclin D 1 , cyclin A , p 27 ( Kip 1 ) , and hyperphosphorylated Rb were decreased , but the levels of cdk 4 , cdk 6 , cdk 2 , p 16 ( INK4a ) , and p 21 ( Cip 1 ) were not affected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
It has long been assumed that the action of cyclin D 1 , as an activator of cdk 4 and cdk 6 and leading to progression through the G 1 phase of the cell cycle , underlies its pathological activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Besides overexpression of cyclin D 1 , the cyclin dependent kinases ( CDK 2 and CDK 4 ) are highly expressed in MCL resulting in the phosphorylation of RB 1 , E2F release , and the cell cycle progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In the presence of p 16 , a quaternary complex is formed between p 34 ( SEI 1 ) , CDK 4 , cyclin D 2 , and p 16 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin D 1 , cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 was measured quantitatively by real time polymerase chain reaction . ^^^ These results indicate that cyclin D 1 may be involved in the regeneration of hepatocytes rather than hepatocarcinogenesis , while Cdk 4 but not Cdk 6 may play an important role in the development of HCC . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , the expression of various cell cycle related proteins , such as Cdk 4 , cyclin D 1 , PCNA , and Cdk 1 was analyzed in the tissues of regenerating rat liver . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunoprecipitation / immunoblot studies revealed that serotonin and angiotensin 2 induced complex formation between CDK 4 , cyclin D 1 , and phosphorylated ERK . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cells in which the level of D type cyclin is dependent on p 27 do not up regulate the activity of their CDK 2 and CDK 4 upon loss of p 27 , and these cells have a negligible amount of p 27 bound to CDK 2 and / or cyclin A / E under normal conditions . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The first group consisted of 95 cases ( 71 . 4 % ) characterized by apoptotic cells showing intensely positive staining for cdk 4 and cyclin D 1 but negative for other proteins ( type A ) . ^^^ When tumor cells retrieved from paraffin embedded tissue were examined by flow cytometry , higher proportions of cells expressing only cdk 4 or cyclin D 1 in type A cases and of cells expressing any cyclin or cdk in type B cases showed a subdiploid DNA content . ^^^ Furthermore , forced overexpression of only cdk 4 or cyclin D 1 induced apoptosis in cultured cells with normal Rb protein , whereas overexpression of any cyclin or cdk induced apoptosis in cells defective for Rb protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Stable overexpression of IL 22 in HepG 2 cells constitutively activates STAT 3 and induces expression of a variety of antiapoptotic ( e . g . , Bcl 2 , Bcl xL , Mcl 1 ) and mitogenic ( e . g . , c myc , cyclin D 1 , Rb 2 , CDK 4 ) proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Caffeine inhibited phosphorylation of retinoblastoma protein at Ser 780 and Ser807 / Ser811 , the sites where retinoblastoma protein has been reported to be phosphorylated by cyclin dependent kinase 4 ( cdk 4 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Effects of 9 cis retinoic acid on cell cycle and expression of cyclin D 1 and cdk 4 in lung cancer cells ] . ^^^ AIM : To study the effects of 9 cis retinoic acid ( 9 cis RA ) on cell cycle and expression of cyclin D 1 and cdk 4 in lung cancer cells . ^^^ L 1 ) was used to treat lung cancer cells for 24 h ; Flow cytometry ( FCM ) was used to detect the percent of G0 / G1 phase and S phase cells of three groups including blank control , DMSO control and 9 cis RA groups ; RT PCR was used to analyze the expression changes of cyclin D 1 and cdk 4 before and after treatment with 9 cis RA in lung cancer cells . ^^^ RESULTS : The percent of G0 / G1 phase cells of 9 cis RA groups was significantly higher than that of the control groups ( P < 0 . 01 or P < 0 . 05 ) and the percent of S phase cells of 9 cis RA groups was lower than that of the control groups ( P < 0 . 01 or P < 0 . 05 ) ; the expression of cyclin D 1 of PG , SPC A 1 and L 78 cells was decreased ( P < 0 . 01 ) and the expression of cdk 4 of PG , A 549 and L 78 cells was also decreased ( P < 0 . 01 ) after treatment with 9 cis RA . ^^^ CONCLUSION : Most of the proliferation and the expression of cyclin D 1 and cdk 4 of PG , A 549 , SPC A 1 and L 78 were inhibited by 9 cis RA . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 expression estimated by a real time reverse transcription polymerase chain reaction ( RT PCR ) method was also increased markedly at an early stage of cirrhosis development but decreased substantially thereafter . mRNA levels of catalytic subunits of cyclin D 1 , cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , did not show significant changes during the development of liver cirrhosis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
While the amounts of the cellular cyclin dependent kinase ( Cdk ) inhibitors p 21 ( Cip 1 ) , p 27 ( Kip 1 ) , and p 16 ( INK4a ) did not change in infected cells , MHV infection in asynchronous cultures induced a clear reduction in the amounts of Cdk 4 and G ( 1 ) cyclins ( cyclins D 1 , D 2 , D 3 , and E ) in both DBT and 17Cl 1 cells and a reduction in Cdk 6 levels in 17Cl 1 cells . ^^^ MHV infection in quiescent 17Cl 1 cells prevented normal increases in Cdk 4 , Cdk 6 , cyclin D 1 , and cyclin D 3 levels after serum stimulation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : cdk 2 kinase assay to examine histone H 1 phosphorylation . cdk 4 kinase assay to examine whether active cdk 4 / cyclin D complexes , capable of phosphorylating Rb , are formed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Based on the concept that tumor suppressor genes are involved in the pathogenesis of urinary bladder carcinogenesis , we analysed the mRNA expression of the retinoblastoma ( Rb ) and p 16 ( CDKN 2 , INK4A , MTS 1 ) genes as well as of the proto oncogene cyclin D dependent kinase 4 ( CDK 4 ) in 71 transitional cell carcinomas ( TCC ) of the urinary bladder in relation to the tumor grades and stages , and with reference to certain lifestyle and occupational risk factors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , in vitro kinase assays using purified proteins demonstrated that the addition of p21 / waf1 to cyclin D2 / cdk4 increased the kinase activity of cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 Cdk4 can overcome the growth suppressive activity of Rb in both cell cycle progression and colony formation assays ; however , while mutants of Rb in which the Cdk 4 docking site has been either deleted or mutated retain growth suppressor activity , they are resistant to inactivation by cyclin D 1 Cdk4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis demonstrated that the protein levels of cyclin A , but not cyclins B , D 1 , D 3 , E , CDK 2 and CDK 4 , decreased after TB treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , Western blot analysis showed decreased expression levels of cyclin D 1 , cyclin E , cyclin A , Cdk 2 , Cdk 4 , and Cdk 6 proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We investigated the hepatic expression of cyclin D 1 , cyclin E , Cdk 2 , Cdk 4 , p 21 , p 27 , p 53 ; the level of bcl 2 , an antiapoptotic protein and of heme oxygenase 1 ( HO 1 ) , a marker of oxidative stress , by Western blot analysis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Therefore , cyclin D 1 and CDK 4 seem to be involved in the control of placental angiogenesis during the third trimester of gestation . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The overall amounts of cdk 6 and cyclin D 3 , and also of cdk 4 and cyclin E , remained unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Etodolac induced p21WAF1 / Cip1 and p27Kip1 expression and inhibited CDK 2 , CDK 4 , CDC 2 , cyclin A and cyclin B 1 expression , but did not affect cyclin D 1 or cyclin E . ^^^ In conclusion , p21WAF1 / Cip1 , p27Kip1 , CDK 2 , CDK 4 , CDC 2 , cyclin A , cyclin B 1 and the MAP kinase signaling pathway are involved in growth inhibition and cell cycle arrest by a selective COX 2 inhibitor in HCC cell lines . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In OC 15 5 cells treated with 15d PGJ 2 , the expression of CDK inhibitor , p 27 ( Kip 1 ) , was up regulated , while that of p 21 ( WAF1 / Cip1 ) , p 18 ( INK4C ) CDK 2 , CDK 4 , and cyclin E was unchanged . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The increase of DNA synthesis is well correlated with the increased levels of cyclin D 1 and cdk 4 that control the G 1 phase , and also with the activities of cell cycle proteins involved in the G 1 to S phase progression , such as cyclin E / A cdk 2 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blotting was used for caspase 3 and PARP , caspase 7 , caspase 9 , cytochrome c , Bcl 2 , Bax , Mcl 1 , cyclinA , cyclin B 1 , cyclin D 1 , cyclin E , CDK 2 , CDK 4 , CDK 6 , P 21 , P 27 , GADD 45 , GADD 153 . ^^^ The expression of cyclin A and cyclin B 1 was markedly decreased and cyclin D 1 levels were slightly lowered in AsPC 1 cells , while cyclin E was not affected and the levels of CDK 2 , CDK 4 , and CDK 6 were unchanged in MiaPaCa 2 and AsPC 1 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
EGCG differentially regulated the expression of genes and proteins ( Bax , p 21 , Retinoblastoma , cyclin D 1 , CDK 4 , Bcl 10 ( L ) ) more than 2 fold , showing a possible gene regulatory role of EGCG . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 could potentiate hATF 5 transcriptional activity independently of its Cdk 4 partner . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The ability of integrins to induce the activation of EGFR and its subsequent regulation of Erk and Akt activation permitted adhesion dependent induction of cyclin D 1 and p 21 , Rb phosphorylation , and activation of cdk 4 in epithelial cells in the absence of exogenous growth factors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Protein levels of cyclin D 2 and Cdk 4 did not change as a result of hCG , whereas cyclin E increased 6 h after hCG . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Biophys . 41 , 131 ] , this study aims to document the influence of 50 Hz , 1 mT magnetic fields ( MF ) , with or without initial gamma ionizing radiation ( IR ) , on the following cell proliferation relevant parameters in human amniotic fluid cells ( AFC ) : cell cycle distribution , expression of the G 1 phase regulating proteins Cdk 4 , cyclin D 1 , p21CIP1 and p16INK4a , and Cdk 4 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Associations between patient survival and immunostaining for 11 representative histologic classifiers ( epidermal growth factor receptor [ EGFR ] , CDK 4 , syndecan 1 , singed like , TTF 1 , keratin 5 , HDAC 2 , docking protein 1 , integrin alpha 3 , P 63 , and cyclin D 1 ) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In situ hybridization ( ISH ) validated microarray data and it also showed that Fox M 1 , cyclin D 2 , and CDK 4 were highly expressed in CNS germinal zones and ectonucleotide pyrophosphatase / phosphodiesterase 2 ( Enpp 2 ) was highly expressed in choroid plexus where stem / progenitor cells are possibly located . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Activated Notch inhibits mitogen induced upregulation of p21Cip1 and delays cyclin D cdk 4 mediated Rb phosphorylation . ^^^ Notch dependent repression of p21Cip1 prevents nuclear localization of cyclin D and cdk 4 . ^^^ The necessity of p21Cip1 for nuclear translocation of cyclin D cdk 4 and S phase entry in endothelial cells was demonstrated by targeted downregulation of p21Cip1 by using RNA interference . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , D 2 and D 3 , and Cdk 4 , Cdk 6 and Rb protein , and Cyclin D 1 mRNA expression were measured in primary patient derived neuroblastoma cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Despite the observed upregulation of cyclin D 2 , no increase in cdk 4 activity was observed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The biological effect of Ganoderma lucidum was demonstrated by cell cycle arrest at G0 / G1 , which was the result of the downregulation of expression of NF kappaB regulated cyclin D 1 , followed by the inhibition of cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The results showed that NaB and / or ATRA blocked cells mainly in the G0 / G1 phase of the cell cycle ; ATRA inhibited the mRNA expression of CDK 6 , CDK 4 , cyclin D 3 and cyclin D 1 ; NaB inhibited the mRNA expression of CDK 2 , cyclin D 2 and cyclin D 1 ; ATRA and NaB inhibited the mRNA expression of CDK 6 , CDK 4 , CDK 2 , cyclin D 1 , cyclin D 2 and cyclin D 3 ; ATRA and / or NaB both stimulated p 21 expression at the mRNA levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot method was used to examine effect of TGF beta 1 on expression of cyclin A , Cyclin D 1 , CDK 2 and CDK 4 in G 1 phase of cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In cells exposed to rapamycin , we observed a dose dependent downregulation of CCND 1 ( cyclin D 1 ) and CDK 4 gene expression and late G 1 cell cycle arrest . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Rb deleted myotubes were efficiently reactivated by forced expression of cyclin D 1 and Cdk 4 , indicating a functionally significant target other than pRb for these molecules . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although the latter was complexed with PCNA , Cdk 2 , Cdk 4 , Cdk 6 , cyclin D 3 , and cyclin E , truncated p 21 was bound only to Cdk 4 and cyclin D 3 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
YC 1 did not modify the expression of cyclin D 1 , cyclin E , CDK 2 , or CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The following genes exhibited moderate changes in methylation : O 6 methylguanine DNA methyltransferase ( MGMT ) ( 20 % , 13 / 65 ) , mutL homolog 1 , colon cancer , nonpolyposis type 2 ( E . coli ) ( hMLH 1 ) ( 18 % , 12 / 65 ) , cyclin dependent kinase inhibitor 2A ( melanoma , p 16 , inhibits CDK 4 ) ( p 16 ( INK4a ) ) ( 10 % , 10 / 65 ) , methylated in tumor 1 ( MINT 1 ) ( 15 % , 10 / 65 ) , methylated in tumor 31 ( MINT 31 ) ( 11 % , 7 / 65 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
These cells developed a G2 / M cell cycle arrest with a concomitant decreased percentage of cells in S phase ( approximately 2 fold ) , associated with an increased expression of p 21 ( WAF 1 ) , p 27 ( KIP 1 ) , as well as cyclin B 1 and decreased levels of CDK 2 , CDK 4 , and E2F4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
However , recent experiments in which the genes encoding all three D type cyclins , the two E type cyclins , cyclin D dependent Cdk 4 and Cdk 6 , or cyclin E dependent Cdk 2 have been disrupted in the mouse germ line have revealed that much of fetal development occurs normally in their absence . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Altered expression of cell cycle regulators Cyclin D 1 , p 14 , p 16 , CDK 4 and Rb in nodular melanomas . ^^^ To investigate whether alterations in Cyclin D 1 , p 14 , CDK 4 and Rb are associated with tumour cell proliferation , tumour progression and patient survival in malignant melanoma , we examined 202 vertical growth phase tumours and 68 corresponding metastases for expression of Cyclin D 1 , p 14 , CDK 4 and Rb , and compared the results with Ki 67 expression , p 16 and p 53 expression , clinico pathological variables , and survival data . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Over expression of E2F 1 , cyclin D 1 , Cdk 2 , Cdk 4 and cyclin A was found in 64 % ( 30 of 46 ) , 43 % ( 26 of 46 ) , 28 % ( 11 of 46 ) , 71 % ( 33 of 46 ) and 63 % ( 29 of 46 ) of HCCs examined respectively and this was correlated with elevation of ERK . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , a significant increase in p 21 mRNA expression and a decrease in cyclin D 1 and Cdk 4 mRNA expression resulted at the same time . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We found that overexpression of wild type FAK promoted exit from G ( 1 ) in monolayer cultures of glioblastoma cells , enhanced the expression of cyclins D 1 and E while reducing the expression of p 27 ( Kip 1 ) and p 21 ( Waf 1 ) , and enhanced the kinase activity of the cyclin D 1 cyclin dependent kinase 4 ( cdk 4 ) complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In addition , the Ras / PI3 K / AKT / Rac / NFkappaB / cyclin D 1 signaling cascade triggered by endogenously released IGF 1 is sufficient to sustain Rb phosphorylation and cdk 4 kinase activity in BON cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Biochip analysis showed that SWCNTs can induce up regulation expression of cell cycle associated genes such as p 16 , bax , p 57 , hrk , cdc 42 and cdc 37 , down regulation expression of cell cycle genes such as cdk 2 , cdk 4 , cdk 6 and cyclin D 3 , and down regulation expression of signal transduction associated genes such as mad 2 , jak 1 , ttk , pcdha 9 and erk . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Independent of its survival function , BLyS enhances the synthesis of cyclin D 2 , in part through activation of NF kappaB , as well as CDK 4 and retinoblastoma protein phosphorylation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Stimulation of alpha1A AR also upregulated the cell cycle regulatory proteins pRb , cyclin D 1 , Cdk 2 , Cdk 4 , and proliferating cell nuclear antigen . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
First , tetrandrine inhibits purified cyclin dependent kinase 2 ( CDK 2 ) / cyclin E and CDK 4 without affecting significantly CDK2 / cyclin A , CDK1 / cyclin B , and CDK 6 . ^^^ Second , tetrandrine induces the proteasome dependent degradation of CDK 4 , CDK 6 , cyclin D 1 , and E2F1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This was accompanied by induction of cell cycle G 1 phase arrest and suppression of cyclin D 1 , cdk 4 , and cdk 2 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 was functional inasmuch as it was complexed with CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , apigenin downregulated cyclin D 1 , D 3 and Cdk 4 and increased p 27 protein levels . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
After 90 day feeding , bladder samples were collected for histopathological diagnoses , and immunohistochemical method was used to characterize the expression of p16Ink4a cyclin D 1 , CDK 4 , EGFr and cyclin E in relation to that of proliferating cell nuclear antigen ( PCNA ) . ^^^ Overexpressions of cyclin D 1 , CDK 4 , EGFr are found in the corresponding lesion . p16Ink4a nuclear staining reduced in proliferative bladders especially with a great quantity of stone . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Early onset of G 1 cell cycle arrest along with upregulation of the cyclin dependent kinase inhibitor p27Kip1 and downregulation of Cdk 2 , Cdk 4 , Cdk 6 , and Cyclin E has also been observed in Jak 3 overexpressing 32Dcl3 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
OBJECTIVE : To study the expression and significance of cyclin E , cyclin D 1 , CDK 4 and p 27 protein in esophageal squamous cell cancer ( ESCC ) and their correlation with tumor differentiation and lymph node metastasis . ^^^ METHODS : Expressions of cyclin E , cyclin D 1 , CDK 4 and p 27 protein in 65 patients with ESCC were quantitatively detected by flow cytometry . ^^^ RESULTS : The expressions of cyclin E , cyclin D 1 , CDK 4 in poorly differentiated ESCC were higher than those in well differentiated ESCC ( P = 0 . 0275 , 0 . 0001 , 0 . 0174 ) . ^^^ There was positive correlation between cyclin E and cyclin D 1 , cyclin D 1 and CDK 4 , but negative correlation between cyclin D 1 and p 27 . ^^^ CONCLUSION : The expressions of cyclin E , cyclin D 1 , CDK 4 and p 27 are closely related to tumor differentiation of ESCC . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This uterine epithelial cell proliferation is preceded by the mobilization of cyclin D 1 from the cytoplasm to the nucleus which , together with CDK 4 , phosphorylates members of the Rb retinoblastoma family of proteins , pRb and p 107 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
From four successful cultures , three showed a high expression of cyclin D 1 , cyclin E , p16NK4A , and p27KIP1 with no variations in cyclin A , cyclin dependent kinase 2 ( CDK 2 ) , and CDK 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Interestingly , cyclin D 3 and cdk 4 selectively interact with phosphorylated p 27 ( kip 1 ) in BL 40 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Growth inhibition correlated with a decrease in serum dependent expression of cyclin D 1 , cyclin A and the cyclin dependent kinase , cdk 4 , key regulators of cell cycle progression through G ( 1 ) phase . ^^^ DeltaB Raf : ER , an inducible estrogen receptor B Raf fusion protein , restored levels of active ERK in anastellin treated cells , rescued levels of cyclin D 1 , cyclin A , and cdk 4 , and rescued [ ( 3 ) H ] thymidine incorporation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Assays using model reporter constructs as well as endogenous target genes showed that the activity of c Myb was inhibited by cyclin D 1 plus CDK 4 or CDK 6 but stimulated by expression of the CDK inhibitors p 16 Ink4a , p 21 Cip1 , or p 27 Kip1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Instead , cAMP phosphorylates and inactivates pRb by inducing the assembly and nuclear translocation of the cyclin D 3 CDK4 p 27 holoenzyme , and then by stimulating the activating phosphorylation of CDK 4 within this complex . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin E and Cdk 2 protein expression and complex formation was not affected by CYC 202 nor was cyclin D 1 , Cdk 4 and c ras mRNA expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In cell culture studies , TGF beta 1 significantly inhibited proliferation of MBEC via downregulation of cyclin D 1 , cdk 4 , and cdk 6 , while TGF beta 1 did not influence the proliferation of ICC cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
By contrast , no significant changes in the levels of cyclin B 1 , CDK 1 or CDK 4 were detected . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Consistent with G ( 1 ) arrest in DU 145 cells , decursin strongly increased protein levels of Cip1 / p21 but showed a moderate increase in Kip1 / p27 with a decrease in cyclin dependent kinases ( CDK ) ; CDK 2 , CDK 4 , CDK 6 , and cyclin D 1 , and inhibited CDK 2 , CDK 4 , CDK 6 , cyclin D 1 , and cyclin E kinase activity , and increased binding of CDK inhibitor ( CDKI ) with CDK . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
All tumor samples expressed normal sized RB 1 , cyclin D 3 , CDK 2 , CDK 4 , p 21 ( CIP 1 ) , and p 27 ( KlP 1 ) proteins , and only a single tumor showed an aberrant protein band for one of these proteins , p 21 ( CIP 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression pattern of key molecules of the Rb and p 53 pathways , such as Rb , cyclin D 1 , CDK 4 , p 16 , p 53 , p 21 and Bcl 2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Synovial tissue from 20 patients with active proliferative RA and 28 patients with RA in remission was immunohistochemically examined for expression of p 53 , p 63 , p 21 , p 27 , p 16 , cyclin D 1 , CDK 4 , RB , E2F , Ki 67 on tissue microarrays and by DNA flow cytometry for cell cycle phases . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cell cycle progression without cyclin D CDK 4 and cyclin D CDK 6 complexes . ^^^ D type cyclins ( cyclin D 1 , D 2 and D 3 ) and their associated cyclin dependent kinases CDK 4 and CDK 6 were thought to represent important , perhaps essential components of the core cell cycle apparatus . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D1 / cyclin dependent kinase 4 ( cdk 4 ) cdk 6 system mediated phosphorylation of retinoblastoma protein was downregulated due to overexpression of p 16 at 24 h after exposure to the lethal dose alone . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In this report , we show that adenovirus mediated expression of merlin in NF 2 deficient tumor cells inhibits cell proliferation and arrests cells at G 1 phase , concomitant with decreased expression of cyclin D 1 , inhibition of CDK 4 activity , and dephosphorylation of pRB . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although MDM 2 overexpression was accompanied by CDK 4 overexpression or absence of cdk 4 inhibitor p 16 in most breast cancer cells , we found remarkably high levels of cyclin A rather than cyclin E in these cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
DA increased number of cells with a G 1 DNA content , decreased BrdU incorporation and simultaneously increased cyclin A but had no effect on cyclin D 2 , D 3 , E , nor on cdk 4 and p 21 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In contrast , most BRCA 2 associated carcinomas grouped in a branch composed by ER / PR / BCL2 positive tumors with a higher expression of the cell cycle proteins cyclin D 1 , cyclin D 3 , p 27 , p 16 , p 21 , CDK 4 , CDK 2 and CDK 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression status of the three cyclin D genes ( CCND 1 , CCND 2 and CCND 3 ) , the two cyclin D dependent kinase genes ( CDK 4 and CDK 6 ) and the p 16 ( INK4a ) gene was studied in a series of 47 Wilms ' tumors , 16 normal mature kidneys and two fetal kidneys . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
When cyclin D 1 was induced after partial hepatectomy , its predominant CDK binding partner was CDK 4 . ^^^ In conclusion , liver development is associated with a switch from cyclin D2 / D3 containing complexes to cyclin D 1 : CDK 4 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Although protein expression levels of cyclin D 1 and p16INK4a cyclin dependent kinase ( Cdk ) inhibitor in HCC tumors were not decreased by vitamin K 5 treatment , those of Cdk 4 were reduced significantly by the treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In many tissues mitogens influence development by stimulating D type cyclins ( D 1 , D 2 , or D 3 ) and activating cyclin dependent kinases ( CDK 4 or CDK 6 ) , which results in progression through the G ( 1 ) phase of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Levels of known Hsp 90 client proteins such as phosphorylated AKT followed by AKT , cyclin D 1 preceding cdk 4 , and craf 1 declined as a result of drug treatment in all three melanoma cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This change is associated with a marked reduction in regulators of S ( cyclin A , cyclin dependent kinase ( cdk ) 2 ) , G2 / M ( cyclin B 1 , cdk 1 , cdc25c ) and G 1 ( cyclin D 1 , cyclin E , cdk 2 , cdk 4 ) phase , and an increase in p 21 and p 27 level . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
During the S phase arrest , analysis of cell cycle regulatory molecules demonstrated that baicalein decreased the levels of cdk 4 , cyclin B 1 and cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The Cyclin dependent kinase ( CDK ) Activating Kinase ( CAK ) is responsible for the activating phosphorylation of CDK 1 , CDK 2 , CDK 4 and CDK 6 and regulation of the cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Both , p 16 , cyclin D 1 , cdk 4 and cdk 6 were immuno colocalized with Ezrin , Rac , Vinculin , alphav integrin , and FAK proteins in the ruffles and lamellipodia of migratory cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This study was undertaken to observe the effect of signal regulatory proteinalpha 1 ( Sirpalpha 1 ) on gankyrin , cyclin D 1 , CDK 4 and Fas expression in Sk hep 1 mouse hepatoma carcinoma cell line . ^^^ The protein expressions of gankyrin , cyclin D 1 , CDK 4 and Fas in various Sk hep 1 lines were determined by Western blotting . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of cell cycle regulatory proteins revealed that TZD decreased the protein levels of proliferating cell nuclear antigen , pRb , cyclin D 1 , and Cdk 4 but increased the levels of p 21 and p 27 in a time dependent manner . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Smad 7 inhibits TGF beta mediated downregulation of c Myc , CDK 4 , and Cyclin D 1 , and suppresses the expression of p 21 ( Cip 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
While CDK 4 levels were unchanged following oligomycin treatment , a dramatic reduction in cyclin D ( 1 ) was observed . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
It was demonstrated in CD34+ cell extracts that there was high catalytic activity of G ( 1 ) cyclin dependent kinases 4 and 6 ( CDK 4 and CDK 6 ) but low activity of CDK 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The ability of NO PKG to inhibit AGE induced cell cycle progression was verified by the observation that SNAP , SNP , and 8 pCPT cGMP inhibited both cyclin D 1 and cdk 4 activation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Thallium acetate did not alter the protein levels of cyclin A and B ; cyclin D 1 , D 2 , and D 3 ; and CDK 4 expression in C 6 glioma cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Aldosterone induced cyclin D 1 and cyclin A promoter activities and protein expressions , as well as the increments of CDK 2 and CDK 4 kinase activities . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
As normal cells entered density dependent arrest , cyclin D 1 decreased while cyclin D 2 was induced and replaced D 1 in Cdk 4 complexes . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 and D 3 were unaffected , while cdk 4 was moderately decreased . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The up regulation of p 21 was followed by the inactivation of cyclin D and the cdk 4 protein , which act at the early G 1 phase , and cyclin E , which acts at the late G 1 phase . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment , which also prevented the increase in cyclin D 1 protein expression , CDK 4 activity , Rb phosphorylation , and the increase in UBF availability . ^^^ Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D 1 dependent CDK 4 activity in the regulation of Rb and ribosomal RNA synthesis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The cell cycle arrest involves downregulation of cyclin D 1 , cyclin E , cyclin dependent kinase ( CDK ) 2 , CDK 4 , and CDK 6 and upregulation of p 15 , p 21 , and p 27 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We observed changes in the expression of vital genes belonging to the cell cycle ( cyclin D 1 and CDK 4 ) and apoptosis ( BNIP 3 , BID , and BCL 2 ) pathway in response to BL 1521 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
D cyclins ( D 1 , D 2 and D 3 ) and their catalytic subunits ( cyclin dependent kinases cdk 4 and cdk 6 ) have a facilitating , but nonessential , role in cell cycle entry . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Independent of tissue type , selenium arrests cells in G 1 phase of cell cycle , inhibits CYCLIN A , CYCLIN D 1 , CDC25A , CDK 4 , PCNA and E2F gene expressions while induces the expressions of P 19 , P 21 , P 53 , GST , SOD , NQO 1 , GADD 153 and certain CASPASES . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Recent experimental evidence shows that active Cdk 4 Cyclin D 1 complexes help cells to pass through the R point , a point of no return , after which the cells become committed to a new round of replication . ^^^ It is widely known that P16INK4a can arrest cells in the G 1 phase , but how the expression of exogenous P16INK4 gene can affect the activity of Cdk 4 Cyclin D 1 remains unclear . ^^^ In this study , using exogenous wild type P 16 gene , antibodies for P 16 , Cdk 4 , Cyclin D 1 and Rb proteins , and primers for these genes , we examined the expression of exogenous wild type P 16 gene and the changes of cell cycle regulatory genes ( Cdk 4 , Cyclin D 1 , and Rb ) in human bladder cancer cells . ^^^ The immunocytochemical results indicated that after the transfection of exogenous wild type P 16 gene , the expression of Cdk 4 , Cyclin D 1 , and Rb were negative in the nuclei , whereas the expression of P 16 significantly increased in the nuclei and the cytoplasm . ^^^ The RT PCR results showed that the transcription of P 16 gene increased significantly after the transfection , whereas the transcription of Cdk 4 , Cyclin D 1 , and Rb decreased . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We show that , in contrast to the Kaposi ' s sarcoma associated herpesvirus ( KSHV ) 5 cyclin , the gammaHV 68 5 cyclin preferentially interacts with cdk 2 and cdc 2 but does not interact with either cdk 4 or cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 up regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK 4 and CDK 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Finally , inhibition of EGFR tyrosine kinase , PKC , Ca2+ channels , or p44 / 42 MAPKs attenuated EGF stimulated cyclin D 1 , cyclin E , cyclin dependent kinase ( CDK ) 2 , and CDK 4 , respectively . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Assessment of cdk 4 , cyclin D 1 and p 27 ( kip 1 ) expression revealed that only cdk 4 expression was increased in the cancers with mutant BAT RII . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Further studies showed that there are differential effects of ERKs , JNKs and p38K , as well as their downstream transcription factor AP 1 , in regulation of expression of cyclin D 1 and CDK 4 and cell cycle alternations induced by silica . ^^^ Cyclin D 1 and CDK 4 were increased in S HELF as compared with those in HELF . ^^^ Inhibition of ERKs activation by AG 126 , JNK by SP 600125 , and AP 1 by curcumin could reduced the induction of cyclin D 1 and CDK 4 . ^^^ These results demonstrate that ERKs and JNKs , but not p38K is responsible for induction of cyclin D 1 and CDK 4 in S HELF , suggesting that overexpression of cyclin D 1 and CDK 4 caused by silica is mediated by ERK , JNK / AP 1signaling pathway . . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Here we report that in prototype small intestine crypt stem cells ( RIEC 6 ) , stimulation with either epidermal growth factor or fetal bovine serum results in an unexpected rapid and sustained Rb phosphorylation at sites Ser 780 , Ser 795 , and Thr 821 which precedes cyclin D 1 expression , cyclin D1 / cdk4 complex formation , and cdk 4 kinase activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Cell killing ability of DL 111 IT was measured by MTT / Trypan blue exclusion method and murine and human tumor models ; cell cycle was analyzed by flow cytometry ; pRb , CDK 4 and Cyclin D 1 expressions were detected by western blotting . ^^^ DL 111 IT induced G 1 arrest and overexpression of pRb , CDK 4 and Cyclin D 1 were observed in HO 8910 cell line , suggesting that cell cycle regulation might contribute to the anticancer property of DL 111 IT . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The latter cells were the most responsive to betulinic acid , showing a selective decline in the cdk 4 protein , without a comparable change in other key cell cycle proteins like cdc 2 , cdk 2 , cdk 7 or cyclin A , prior to apoptosis associated PARP fragmentation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin A , cyclin B , cyclin D 1 , cdk 2 , cdk 4 , cdc 2 , proliferating cell nuclear antigen ( PCNA ) , p 21 ( Cip / WAF1 ) , and p 27 was examined with immunoblotting analysis . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 was much more abundant in the infant than adult cells , but there was no difference according to the expression of cdk 4 , cdk 2 , cyclin E and cdk inhibitors ( p 16 ( Ink 4 ) ( p 16 ) , p 21 ( Cip1 / Waf1 ) ( p 21 ) and p 27 ( Kip 1 ) ( p 27 ) ) . 8 OHdG became high soon after cultivation , while it rapidly went down after day 2 both in the infant and adult cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Several antigens were assessed immunohistochemically ( pRb 1 , p16INK4A , cyclin D 1 , cdk 4 , estrogen receptor ( ER ) , progesterone receptor ( PR ) , androgen receptor ( AR ) , p 53 , Ki 67 , p27KIP1 , PTEN , hMLh 1 , phospho AKT , collagen 4 , leptin and CD 90 ) in both tumors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expressions of cyclin D 1 and c myc in HL 60 are suppressed by 8 chloroadenosine , whereas the cyclin dependent kinases inhibitor p 21 ( WAF1 / CIP1 ) is up regulated . 8 Chloroadenosine has less effect on the expressions of cyclin dependent kinase ( cdk ) 2 and cdk 4 , G ( 1 ) phase cyclin dependent kinases , and only moderately induces the expression of transforming growth factor beta 1 ( TGFbeta 1 ) and the mitotic inhibitor p 27 ( KIP 1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Neither compound altered cyclin D 1 and cdk 4 in MCF 7 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Down regulation of cell cycle regulatory components ( CDK 4 , cyclin B , E2F , and phosphorylated Rb ) were observed under similar conditions . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunoblot analysis revealed that PFE treatment of PC 3 cells resulted in ( 1 ) induction of Bax and Bak ( proapoptotic ) ; ( 2 ) down regulation of Bcl 10 ( L ) and Bcl 2 ( antiapoptotic ) ; ( 3 ) induction of WAF1 / p21 and KIP1 / p27 ; ( 4 ) a decrease in cyclins D 1 , D 2 , and E ; and ( 5 ) a decrease in cyclin dependent kinase ( cdk ) 2 , cdk 4 , and cdk 6 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Molecular studies showed that G 1 arrest was associated with a decrease in cyclin D 1 , cyclin D 3 , cyclin E , cyclin dependent kinase ( CDK ) 4 , CDK 6 and CDK 2 protein levels , and CDK 2 and CDK 4 kinase activity , together with an increase in CDK inhibitors ( CDKIs ) Kip1 / p27 and Cip1 / p21 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Pre treatment of AP had no evident effect on p 27 , CDK 4 and Cyclin D 1 protein . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Distinct specificities of pRb phosphorylation by CDK 4 activated by cyclin D 1 or cyclin D 3 : differential involvement in the distinct mitogenic modes of thyroid epithelial cells . ^^^ Unexpectedly , partly different site specificities of pRb kinase activity , leading to similar differences in the phosphorylation pattern of pRb in intact cells , were associated with cyclin D 3 CDK4 bound to p 27 in TSH stimulated cells , or with CDK 4 bound to p 21 in growth factor stimulated cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Further supporting this finding , synchronization studies of Hela cells in various cell cycle phases suggest that A 1 receptor expression is suppressed in G ( 2 ) / M cells and depletion of A 1 receptor expression by siRNA produced differential expression of several key cell cycle regulators , i . e . , accumulation of the cyclin dependent kinase inhibitor p 27 with concomitant reduction of CDK 4 and cyclin E proteins . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
After analyzing the cellular proteins involving in regulation of cell cycle progression , we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D 3 level of mRNA transcription and expression , and phosphorylation of retinoblastoma ( Rb ) protein at ser 795 and ser809 / 811 , not with the expression of cyclin D 1 , D 2 , cdk 4 and cdk 6 in HEK 293 cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Analysis of the cell cycle regulatory proteins demonstrated that squamocin did not change the steady state levels of Cdk 2 , Cdk 4 , cyclin A , cyclin B 1 , cyclin D 3 and cyclin E , but decreased the protein levels of Cdk 1 and Cdc25C . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Fisetin decreased the activities of cyclin dependent kinases ( CDK ) 2 and CDK 4 ; these effects were likely attributable to decreases in the levels of cyclin E and D 1 and an increase in p 21 ( CIP1 / WAF1 ) levels ( P < 0 . 05 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mechanistic studies revealed that silibinin induces Kip1 / p27 but decreases cyclin D 1 , cyclin D 3 , cyclin E , cyclin dependent kinase ( CDK ) 2 , and CDK 4 levels in both cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Androgen receptor ( AR ) , cyclin D 1 , and cdk 4 , induced by R 1881 , are downregulated by DIM . ^^^ DIM downregulates phosphorylated Akt and phosphatidyl inositol 3 kinase and downstream inhibition of cyclin D 1 and cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
DIM also induced a G 1 arrest in DU 145 cells by flow cytometry and downstream concurrent inhibition of cell cycle parameters such as cyclin D 1 , cdk 4 , and cdk 6 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
To analyze the cell kinetics of ulcerative colitis ( UC ) associated dysplasia , cyclin A , cyclin D 1 , cyclin E , cdk 2 , cdk 4 , p 21 ( Waf 1 ) , and p 27 ( Kip 1 ) were immunohistochemically examined , in comparison with sporadic tubular adenomas . ^^^ In tubular adenomas , cyclin A , cdk 4 , p 27 ( Kip 1 ) , and p 21 ( Waf 1 ) were all expressed in the upper parts of the crypts . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Study of the key regulators of cell cycle progression by Western blot analysis showed that the expression of the cyclin dependent kinase inhibitor ( CDKI ) p 27 ( kip 1 ) , but not that of p 21 ( cip 1 ) , was enhanced , whereas that of c Myc , cyclin E , cyclin D 2 , and cyclin dependent kinases 2 and 4 ( CDK 2 and CDK 4 ) was decreased when these cells were treated with TZD 18 ( 10 or 20 microM ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In a further study , we stably transfected antisense cyclin D 1 and antisense CDK 4 plasmid into HELF . ^^^ The inhibition of cyclin D 1 expression and the inhibition of CDK 4 expression significantly impaired the B ( a ) P induced overexpression of E2F 1 respectively . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 is a multifunctional protein that activates CDK 4 and CDK 6 , titrates Cip / Kip CDK inhibitors to increase CDK 2 activity , and modulates the function of certain transcription factors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
ATP increased expression levels of cyclin dependent kinase ( CDK ) 2 , CDK 4 , and cyclin E , which were blocked by suramin , reactive blue 2 , MRS 2179 , MRS 2159 , and nifedipine . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Whereas N protein could directly bind to cyclin D and inhibit the activity of CDK 4 cyclin D complex ; inhibition of CDK 2 activity appeared to be achieved in two different ways : indirectly by down regulation of protein levels of CDK 2 , cyclin E , and cyclin A and by direct binding of N protein to CDK 2 cyclin complex . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This was supported by down regulation of cyclin D 1 , cdk 4 , and cdk 6 in rap1GAP transfected SCC cells . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunohistochemical staining for GAS , SS , cyclin D 1 , cyclin E , cyclin A , cyclin B 1 , CDK 2 and CDK 4 was performed according to the standard streptavidin biotin peroxidase ( S P ) method . ^^^ Cyclin D 1 , cyclin E , cyclin A , cyclin B 1 , CDK 2 , CDK 4 expressions in the three GAS and SS groups were assessed . ^^^ There was a significant positive correlation between the integral ratio of GAS to SS and the semi quantitative integral of cyclin D 1 , cyclin E , cyclin A , CDK 2 , CDK 4 ( P < 0 . 05 , ( D 1 ) r ( s ) = 0 . 252 ; P < 0 . 01 , ( E ) r ( s ) = 0 . 387 ; P < 0 . 01 , ( A ) r ( s ) = 0 . 466 ; P < 0 . 01 , ( K 2 ) r ( s ) = 0 . 519 ; P < 0 . 01 , ( K 4 ) r ( s ) = 0 . 434 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The sodium butyrate induce cell cycle arrest was associated with the decrease of Cdc 2 , Cdk 4 and cyclin A in BCBL 1 cells without altering the protein levels of p 21 ( CIP1 / WAF1 ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Our aim was to analyse 18 MCL cases including four BV MCL for their clinicopathological features , proliferation index , cyclin D 1 and CDK 4 expression and interphase fluorescence in situ hybridization ( FISH ) pattern . ^^^ Moreover , the BV MCL cases were characterized by a combined high percentage of cells expressing cyclin D 1 and / or CDK 4 with a proliferation ( MIB 1 Ki 67 ) index above 50 % . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
RESULTS : After hepatectomy , the cirrhotic remnant expressed significantly lower levels of cyclin D 1 , its kinase partner , cdk 4 , and cyclin E as compared to the controls up to 72 h post hepatectomy . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of total cell lysates revealed no alteration in the protein expression of cyclin A , cyclin D , cyclin E , cyclin dependent kinase ( CDK ) 2 , or CDK 4 due to t10c12 treatment . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cell cycle analysis revealed that the fraction induced cell cycle arrest by significant decrease of S phase , which was associated with the induction of cdk inhibitors p 21 and the suppression of cdk 4 and cyclin D 1 activity . ^^^ Compared to malignant tumor cells , nonmalignant cells were less sensitive to the fraction for the suppression of cell growth and regulation of bax , p 21 , cyclin D 1 , and cdk 4 expression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , the down regulation of the cyclin E and CDK 2 was clearly observed in GM 3 treated HCT 116 cells , but the down regulation of cyclin D 1 and CDK 4 was not . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
AG 490 inhibited the growth of HTLV 1 infected T cell lines and primary ATL cells by inducing G 1 cell cycle arrest mediated by altering the expression of cyclin D 2 , Cdk 4 , p 53 , p 21 , Pim 1 and c Myc , and by apoptosis mediated by the reduced expression of c IAP 2 , XIAP , survivin and Bcl 2 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Many mechanisms may be responsible for activating the RB Cyclin D 1 pathway , including activating ( CDK 4 ) and inactivating mutations ( p16INK4A ) , deletions ( RB and p16INK4A ) , amplifications ( CCND 1 and CDK 4 ) , silencing methylation ( p16INK4A and RB ) , and hyper phosphorylation ( RB ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Oral intake of apigenin resulted in dose dependent ( a ) increase in the protein expression of WAF1 / p21 , KIP1 / p27 , INK4a / p16 , and INK4c / p18 ; ( b ) down modulation of the protein expression of cyclins D 1 , D 2 , and E ; and cyclin dependent kinases ( cdk ) , cdk 2 , cdk 4 , and cdk 6 ; ( c ) decrease in retinoblastoma phosphorylation at serine 780 ; ( d ) increase in the binding of cyclin D 1 toward WAF1 / p21 and KIP1 / p27 ; and ( e ) decrease in the binding of cyclin E toward cdk 2 in both types of tumors . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Furthermore , down regulation of CDK 2 , CDK 4 , and cyclin D 1 was observed in PC 3 cells treated with 1 , 000 nmol / L of MONCPT , whereas overexpression of CDK 7 , CDK 1 , and cyclin B 1 was seen in PC 3 cells treated with 10 and 100 nmol / L of MONCPT . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The dopamine induced decrease in cyclin E , cyclin dependent protein kinase 2 ( CDK 2 ) , and cyclin D 1 , CDK 4 were blocked by pertussis toxin ( G protein inhibitor ) , SQ 22536 , neomycin , bisindolylmaleimide 1 ( PKC inhibitor ) , SB 203580 ( p 38 MAPK inhibitor ) , PD 98059 ( p44 / 42 inhibitor ) , and SP 600125 ( SAPK / JNK inhibitor ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK 4 kinase activity . ^^^ Cell lines and tissue samples displayed constitutive activation of the cyclin D 1 signaling cascade , as evidenced by strong expression of CDK 4 , Rb phosphorylation , and cyclin D1 / CDK4 coassociation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
The expressing levels of cyclin D 1 , CDK 4 , Fas , beta catenin and gankyrin in various cell lines were determined with Western blotting . ^^^ RESULTS : Sirpalpha 1 could significantly decrease the expression of cyclin D 1 , beta catenin and gankyrin , but it could n ' t affect the expression level of CDK 4 and Fas . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
We have shown that the G 1 cell cycle regulatory proteins cyclin D 1 and Cdk 4 play important roles in cardiomyocyte hypertrophy . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
More importantly , we demonstrate that BARA / LIN 9 also acts downstream of cyclin D / CDK4 in mammalian cells since ( 1 ) its antiproliferative effect is partially blocked by coexpression of cyclin D 1 , and ( 2 ) a mutant form that lacks the first 84 amino acids rescues several phenotypic alterations observed in mice null for cdk 4 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Cyclin D dependent Cdk 4 and Cdk 6 were expressed in most of a panel of six human rhabdomyosarcoma derived cell lines . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G ( 1 ) S transition and proteins that regulate apoptosis including Rb , E2F1 , cyclin D 1 , CDK 4 , CDK 6 , p 27 ( KIP 1 ) , p 21 ( WAF1 / CIP1 ) , p 53 , Mdm 2 , Bcl 2 , and Bax . ^^^ The positive phenotypes identified were as follows : Rb , 39 . 1 % ; E2F1 , 69 . 6 % ; cyclin D 1 , 30 . 4 % ; CDK 4 , 100 % ; CDK 6 , 30 . 4 % ; 39 . 1 % ; p 27 ( KIP 1 ) , 47 . 8 % ; p 21 ( WAF1 / CIP1 ) , 39 . 1 % ; p 53 , 43 . 5 % ; Mdm 2 , 17 . 4 % ; Bcl 2 , 91 . 3 % ; and Bax , 100 % . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Fraction induced apoptosis ( P < 0 . 05 ) was detected in all cell lines , and this was associated with the induction of proapoptotic bax protein and cdk inhibitors ( p 21 ) and the suppression of cdk 4 and cyclin D 1 activity . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
High glucose level also increased cyclin D 1 , cyclin E , cyclin dependent kinase ( CDK ) 2 , and CDK 4 protein levels , which is cell cycle regulatory proteins acting in G 1 S phase of cell cycle . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Inhibition of either MLCK or Rho kinase blocked sustained ERK signaling , but only Rho kinase inhibition allowed for the induction of cyclin D 1 and activation of cdk 4 via Rac / Cdc42 . ^^^ Overall , our results indicate that Rho kinase dependent stress fiber formation is required for sustained activation of the MEK / ERK pathway and the mid G ( 1 ) phase induction of cyclin D 1 , but not for other aspects of cdk 4 or cdk 2 activation . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
METHODS : Genes for the CDKIs p 16 ( INK4a ) and p 18 ( INK4c ) , a constitutively active form of retinoblastoma ( RB ) gene product , cyclin D 1 , and CDK 4 , were transferred into RA synovial fibroblasts ( RASFs ) . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Finally , immunoprecipitation studies showed that CDK 6 is a major binding partner for cyclin D 3 , whereas CDK 4 preferentially associated with cyclin D 1 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Membrane depolarization induced by 50 mM KCl for 5 min significantly increased SH SY5Y cell numbers and thymidine incorporation at 24 h after depolarization , and increased the phosphorylation and expression of retinoblastoma protein ( RB ) , the activity of Cdk 2 ( without changing the activities of Cdk 4 and Cdk 6 ) , and the expressions of cyclin A and cyclin E . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This survival advantage was associated to a BCR dependent activation profile leading to induction of cyclin D2 / cyclin dependent kinase 4 ( cdk 4 ) expression and G 1 cell cycle progression . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
Restoration of Fhit expression led to down regulated cyclophilin A protein expression and subsequently prevented cyclophilin A induced up regulation of cyclin D 1 , Cdk 4 , and resultant cell cycle progression ( G ( 1 ) S transition ) , which was independent of Ca ( 2+ ) / calmodulin dependent kinase inhibitor , KN 93 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
In rats , treatment with 2 ME abrogated injury induced neointima formation ; decreased proliferating SMCs ; downregulated expression of proliferating cell nuclear antigen ( PCNA ) , c myc , cyclin D ( 1 ) , cyclin B ( 1 ) , phosphorylated Akt , phosphorylated ERK1 / 2 , p 21 , and pRb ; inhibited cdk 1 and cdk 4 activity ; and upregulated expression of cyclooxygenase ( COX ) 2 and p 27 . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
This effect was associated with the downregulation of cyclin D 1 , cdk 4 and Akt , depletion of Bid , and activation of the intrinsic / mitochondrial caspase pathway . ^^^
Interacting proteins: P11802 and P12004	Pubmed	SVM Score :0.0
However , t10c12 did not affect the expression of cyclin dependent kinase ( CDK ) 2 , CDK 4 , or cyclin E . t10c12 increased p 21 ( CIP1 / WAF1 ) bound to CDK 2 and attenuated CDK 2 activity . ^^^