Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.63646066
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 . 0.63646066^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.63247239
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 . 0.63247239^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
A novel cytoplasmic substrate for cdk 4 and cdk 6 in normal and malignant epithelial derived cells . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
These events follow the initial signals stimulated through the engagement of the T cell receptor and include activation of the cyclin dependent kinases Cdk 6 , Cdk 4 , and Cdk 2 , as well as a transient phosphorylation of the retinoblastoma gene product ( p110Rb ) by one or several of these proteins . ^^^ A progression signal such as that delivered by interleukin 2 then induces a second phase of Cdk 6 , Cdk 4 , and Cdk 2 activation , along with sustained phosphorylation of p110Rb in the activated T cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
CD 40 signaling mediated induction of Bcl XL , Cdk 4 , and Cdk 6 . ^^^ In this study , using a murine B cell WEHI 231 line that undergoes apoptosis by the cross linking of surface Ag receptors ( sIgM ) , we have demonstrated that CD 40 signalings are linked to induction of the Bcl xL , Cdk 4 , and Cdk 6 proteins whose expression was significantly suppressed by the apoptotic signal through sIgM . ^^^ By CD 40 signalings , both Cdk 4 and Cdk 6 resume their normal expression levels , which are sufficient for passing the restriction point in G 1 even in the presence of the apoptotic signals mediated by sIgM . ^^^ These results suggest that cooperation of Bcl xL , Cdk 4 , and Cdk 6 induced by CD 40 signaling plays a key role in CD 40 mediated selective growth of B cells . . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Induced by growth factor stimulation , D type cyclins assemble with cyclin dependent kinases CDK 4 and CDK 6 to form holoenzymes that facilitate exit from G 1 by phosphorylating key substrates , including the retinoblastoma protein . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Since most hematological malignancies except ALL are infrequently associated with p16INK4A and retinoblastoma ( Rb ) gene alteration it seems worthwhile to explore cdk 4 and cdk 6 expression to determine whether or not the disruption of the p16INK4A / Rb / cdk4 / cdk6 regulatory loop might play a role in their pathogenesis . . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^ Proliferating Mv1Lu mink lung epithelial cells and human keratinocytes contain high levels of the universal Cdk inhibitor p27Kip1 distributed in complexes with Cdk 2 , Cdk 4 , and Cdk 6 . ^^^ Addition of the antimitogenic cytokine transforming growth factor beta ( TGF beta ) elevates expression of the Cdk4 / 6 specific inhibitor p15Ink4B and induces the release of p 27 from Cdk 4 and Cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ In mouse MEL erythroleukemia cells , p16INK4a associates preferentially with cdk 6 under conditions where cdk 4 and cdk 6 are coexpressed at equivalent levels . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The RB+ / + and RB / ME fibroblasts expressed similar protein levels of D type cyclins , cdk 4 , and cdk 6 , showed analogous spectra and abundance of cellular proteins complexed with cdk 4 and / or cyclins D 1 and D 2 , and exhibited comparable associated kinase activities . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Identification of human and mouse p 19 , a novel CDK 4 and CDK 6 inhibitor with homology to p16ink4 . ^^^ 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 . ^^^ In T cell hybridoma DO11 . 10 , p 19 was found in association with CDK 4 and CDK 6 in vivo , although its association with Nur 77 is not clear at this point . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
D type cyclins , in association with the cyclin dependent kinases Cdk 4 or Cdk 6 , promote progression through the G 1 phase of the cell cycle by phosphorylating the retinoblastoma protein ( RB ) . ^^^ The activities of Cdk 4 and Cdk 6 are constrained by inhibitors such as p 16 , the product of the CDKN 2 gene on human chromosome 9p21 ( refs 12 14 ) . ^^^
Interacting proteins: Q00534 and P11802	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 ) . ^^^ However , in cells in which the function of Rb has been compromised , either by naturally arising mutations or through binding to proteins encoded by DNA tumour viruses , Cdk 4 and Cdk 6 are not associated with D cyclins . ^^^ Since Rb negative cells express high levels of p 16 , we suggest that in these cells p 16 competes with D cyclins for binding to Cdk 4 and Cdk 6 and prevents formation of active complexes . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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 ) . ^^^ We have isolated cDNA sequences corresponding to the MTS 2 genomic fragment that encodes the CDK 4 and CDK 6 associated p 14 protein . ^^^ 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 ) . ^^^ Both in vivo and in vitro , p 18 interacts strongly with CDK 6 , weakly with CDK 4 , and exhibits no detectable interaction with the other known CDKs . ^^^ 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: Q00534 and P11802	Pubmed	SVM Score :0.0
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 contrast , Cdk 4 was expressed at high levels in several tumor cell lines and Cdk 6 was ectopically expressed in two sarcoma lines , suggesting a possible involvement of these two Cdks in oncogenesis . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Normal progression through G 1 is promoted by the activity of the cyclin dependent protein kinases CDK 4 and CDK 6 ( ref . 2 ) , which are inhibited by the protein p16INK4 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
This timing suggests that cdk 6 , and by analogy its homolog cdk 4 , links growth factor stimulation with the onset of cell cycle progression . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
All three D type cyclins can be shown to associate with two specific kinases , cdk 4 and cdk 6 , providing at least six possible combinations . ^^^ Although complexes involving cdk 4 or cdk 6 were readily observed in many of the cell lines , no complexes were detectable in human cells harbouring DNA tumour virus oncoproteins or in which the retinblastoma gene product ( pRb ) is mutated or missing . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Second , in Calu 3 cells , a His to Tyr substitution at codon 83 produced a variant with a shortened half life that was unable to form complexes with cdk 4 or cdk 6 . ^^^ Although this variant formed complexes with cdk 4 and cdk 6 , it had a profoundly reduced half life , producing low steady state levels of p16INK4A and abundant levels of free cdks . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Its product inhibits the phosphorylation of the retinoblastoma protein ( pRb ) by CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
DIA / LIF stimulated ES cells are not growth arrested by overexpression of p16Ink4a , a specific inhibitor of CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The growth suppressing activity of the retinoblastoma suspectibility gene product , pRb , is down regulated by cyclin dependent kinases 4 and 6 ( CDK 4 and CDK 6 ) whose kinase activity is negatively regulated by CDK inhibitors of the p 16 family . ^^^ Thus , while they share a very similar biochemical mechanism of inhibiting the kinase activity of CDK 4 and CDK 6 , members of the p 16 gene family play different roles in controlling cell proliferation and suppressing tumor growth . . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Here , we found that Tax binds to a cyclin dependent kinase inhibitor , p16INK4A , which has ankyrin motifs similar to 1 kappa B . p16INK4A binds to the cyclin dependent kinases , CDK 4 and CDK 6 , and inhibits their activity , resulting in suppression of G 1 phase progression . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Both cdk 4 and cdk 6 phosphorylate the retinoblastoma protein ( pRb ) and are thought to be required for cell proliferation . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence . p16CDKN2 specifically binds to and inhibits the cyclin dependent kinases CDK 4 and CDK 6 , which function as regulators of cell cycle progression in G 1 by contributing to the phosphorylation of the retinoblastoma protein ( pRB ) . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Isolation and characterization of p19INK4d , a p 16 related inhibitor specific to CDK 6 and CDK 4 . ^^^ We have isolated cDNA sequences , INK4d , encoding a 19 kDa protein that is associated with CDK 6 in several hematopoietic cell lines . p 19 shares equal similarity and a common ancestor with other identified inhibitors of the p16 / INK4 family . p 19 interacts with and inhibits the activity of both CDK 4 and CDK 6 and exhibits no detectable interaction with the other known CDKs . p 19 protein is present in both cell nuclei and cytoplasm . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
This p 53 mediated growth arrest can be abrogated by overexpression of cdk 4 and cdk 6 but not cdk 2 or cyclins , leading to continuous proliferation of transfected cells in the presence of wild type p 53 and p2l . ^^^ Kinase inactive counterparts of cdk 4 and cdk 6 also rescue these cells from growth arrest , implicating a noncatalytic role for cdk 4 and cdk 6 in this resistance to p 53 mediated growth arrest . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^ The amino acid residues of p 16 important for its interaction with cdk 4 and cdk 6 and for the inhibition of pRb phosphorylation were defined by an alanine substitution series of peptides . ^^^ CONCLUSIONS : These results demonstrate that a p 16 derived peptide can mediate three of the known functions of p 16 : firstly , it interacts with cdk 4 and cdk 6 ; secondly , it inhibits pRb phosphorylation in vitro and in vivo ; and thirdly , it blocks entry into S phase . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In the glioblastomas with no alterations of CDKN2A , CDK 4 or RB 1 , several other genes ( CCND 1 , CCND 2 , CCND 3 , CDK 6 , E2F , CDK 7 , MYC and MYCN ) whose products take part in cell cycle regulation were examined . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ In addition , p 27 associates with three different CDKs : CDK 2 , CDK 4 , and CDK 6 . ^^^ The amount of CDK 4 and CDK 6 associated with p 27 does not change in a cell cycle dependent fashion ; in contrast , the amount of CDK 2 associated with p 27 is lowest in early G 1 cells and increases to a maximum in mid G 1 phase , reaching a steady state level in late G 1 phase cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Moreover , the growth of JKB 2 cells was partially inhibited by TGF beta or IL 7 , accompanied by decreased CDK 4 and CDK 6 expression , increased p2l and p 27 expression , decreased p 27 binding to CDK4 / CDK6 , and increased binding of p 27 to CDK 2 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The p 16 protein has been identified as a tumor suppressor that functions by inhibiting the cyclin dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
This treatment resulted in a slight but detectable reduction in the protein levels of cdk 6 but did not reduce the levels of cdk 2 , cdk 4 , or the D cyclins . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Induction of p18INK4c and its predominant association with CDK 4 and CDK 6 during myogenic differentiation . ^^^ In murine C2C12 myoblast cells , G 1 CDK enzymes ( CDK 2 , CDK 4 , and CDK 6 ) associate with four CDK inhibitors : p18INK4c , p19INK4d , p 21 , and p27Kip1 . ^^^ Induction of p 18 correlated with increased and sequential complex formation first increasing association with CDK 6 and then with CDK 4 over the course of myogenic differentiation . ^^^ All of the CDK 6 and half of the CDK 4 were complexed with p 18 in terminally differentiated C2C12 cells as well as in adult mouse muscle tissue . ^^^ Finally , kinase activity of CDK 2 and CDK 4 decreases as C2C12 cells differentiate , whereas the CDK 6 kinase activity is low in both proliferating myoblasts and differentiated myotubes . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ Downstream targets of Rb , such as the E2F1 transcription factor , can promote cell cycle progression , whereas inhibitors of CDK 4 and CDK 6 , such as p16CDKN2a , can block G 1 progression . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The p16INK4 family of CDK inhibitors specifically prevent the phosphorylation of the retinoblastoma susceptibility gene product , pRb , by inhibiting the kinase activity of CDK 4 and CDK 6 , thereby keeping pRb in its active form as a growth suppressor . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb , we examined the expression levels and interaction of the Rb kinases , CDK 4 and CDK 6 , and the cyclin dependent kinase inhibitors p 21 and p 16 in senescent HDFs . ^^^ In senescent HDFs , p 16 was shown to be complexed to both CDK 4 and CDK 6 . ^^^ Immunodepletion analysis of p 21 and p 16 from the senescent cell extracts revealed that p 16 is the major CDK inhibitor for both CDK 4 and CDK 6 kinases . ^^^ Immunoprecipitation of CDK 4 and CDK 6 and their associated proteins from radiolabeled extracts from senescent HDFs showed no other CDK inhibitors . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Normal melanocytes and all melanoma lines expressed Cdk 4 , Cdk 6 , and cyclins D 1 and D 3 . ^^^ 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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
NMR structural characterization of the CDK inhibitor p19INK4d . p19INK4d is a 165 amino acid protein that belongs to the INK 4 family of CDK 4 and CDK 6 inhibitors . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
After the shift , cdk 4 levels remained constant and cdk 6 levels decreased in all cell types ; cdk 2 minimally increased only in SVLT cells . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Moreover , CDK 6 ( but not CDK 4 ) was detectable in all the populations investigated . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ 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: Q00534 and P11802	Pubmed	SVM Score :0.0
In contrast , cdk 4 and cdk 6 were present at similar levels in the nuclear extracts from both growth and differentiation induced cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Cdc 37 protein specifically interacts with Cdk 4 and Cdk 6 , but not with Cdc 2 , Cdk 2 , Cdk 3 , Cdk 5 and any of a number of cyclins tested . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
IFNgamma inhibits the kinase activities of cdk 2 , cdk 4 and cdk 6 within 24 h of treatment . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Here we report that TGF beta can also cause the inhibition of Cdk 4 and Cdk 6 by increasing their level of tyrosine phosphorylation . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
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: Q00534 and P11802	Pubmed	SVM Score :0.0
The decline in the expression of p27Kip1 and sequestering of the inhibitory protein by cdk 4 and cdk 6 correlated with the increase in cdk 2 kinase activity during the G 1 phase . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Immature 32Dcl3 myeloid cells ( 32D ) proliferating in the presence of interleukin 3 ( IL 3 ) normally express cyclins D 2 and D 3 , which assemble into binary holoenzyme complexes with their catalytic subunits , CDK 4 and CDK 6 . ^^^ We derived 32D cells in which the expression of p19INK4d , a specific polypeptide inhibitor of CDK 4 and CDK 6 , is regulated by the heavy metal inducible sheep metallothionein promoter . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
These alterations in p 21 expression in MM cells were associated with changes in p 21 binding to CDK 2 , CDK 4 , and CDK 6 ; CDK 2 , CDK 4 , and CDK 6 kinase activities ; and phosphorylation of pRB . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Here , we found that Tax binds to a cyclin dependent kinase inhibitor , p16Ink4a . p16Ink4a binds to cyclin dependent kinases , CDK 4 and CDK 6 , and inhibits their activity , resulting in suppression of G 1 phase progression . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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 ) . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
These data show that the functions of Cdk 4 and Cdk 6 are not redundant and that Cdk 6 and Cdk 2 activities are regulated by 1 , 25 dihydroxyvitamin D3 . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In contrast to p 15 , CDK 4 and CDK 6 did not coimmunoprecipitate p 10 in transient expression assays in COS 7 cells . ^^^ Furthermore , overexpression of p 10 together with p 15 in COS 7 cells did not interfere with the complex formation of p 15 with CDK 4 or CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Assay for activity of mammalian cyclin D dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
We also have determined the in vitro kinase activities of cdc 2 , CDK 2 , CDK 4 , CDK 5 and CDK 6 immunocomplexes in fetal , neonatal and adult myocytes . ^^^ There was a consistent and significant loss of cdc 2 , CDK 2 , CDK 4 and CDK 6 kinase activities in adult cardiac cell lysates ( 5 . 3 , 10 . 6 , 1 . 5 and 1 . 9 fold decreases , respectively ) when compared to neonatal samples ( P < 0 . 05 ) ; CDK 5 activity showed a similar trend but failed to reach significance . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The p 16 mutants E120K and R144C formed complexes with CDK 4 and CDK 6 in cells and inhibited cell growth as effectively as wt p 16 ( 20 fold ) while the mutant proteins that did not complex with detectable levels of CDK 4 or CDK 6 only inhibited growth 0 . 25 and five fold ( G101W and D 141 , respectively ) or not at all ( H83Y and DA 4 ) . ^^^ The amino acid substitutions in mutants G101W and H83Y not only disrupted CDK 4 and CDK 6 binding , but decreased the protein half lives by two and three fold , respectively , compared to wt p 16 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In contrast , the same or a larger increase in p 27 levels did not inhibit Cdk 4 or its homologue Cdk 6 , despite extensive binding to these kinases . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Arg24Pro appeared to bind to CDK 6 , but not to CDK 4 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Its product , p 16 , binds specifically to CDK 4 and CDK 6 in vitro and in vivo , inhibiting their kinase activity . ^^^ Immunoprecipitation of p 16 in these lines , followed by Western blotting to detect the coprecipitation of CDK 4 and CDK 6 , revealed that p 16 was functionally compromised in all cell lines but the one that carried a heterozygous CDKN2A mutation . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
However , with lowering of temperature from 40 degrees C to permissive conditions ( 31 degrees C ) , the percentage of JKB p16MT cells in G 1 phase and binding of p 16 to CDK 4 and CDK 6 increased , with associated decreases in CDK 4 and CDK 6 kinase activities , and dephosphorylation of retinoblastoma protein ( pRB ) . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
To test this hypothesis , we used the RNA alphavirus Sindbis to express three known cyclin dependent kinase inhibitors ( CKIs ) , p 16 ( ink 4 ) , p 21 ( waf / cip ) , and p 27 ( kip 1 ) , and dominant negative mutant forms of four known G 1 cyclin dependent kinases ( CDKs ) , Cdk 2 , Cdk 3 , Cdk 4 , and Cdk 6 , in primary cultured rat superior cervical ganglion sympathetic neurons . ^^^ In addition , we show that expression of dominant negative forms of Cdk 4 or Cdk 6 , but not Cdk 2 or Cdk 3 , protects NGF deprived sympathetic neurons from death . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The p19INK4d and p18INK4c proteins formed complexes with either CDK 4 or CDK 6 in a temporal pattern consistent with the results of in situ hybridization . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ Interestingly , upregulation of either cdk 4 or cdk 6 was demonstrated in 85 % of cases . . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Inactivation of p16INK4 , an inhibitor of cyclin dependent kinases 4 ( CDK 4 ) and 6 ( CDK 6 ) , may be essential for oncogenesis in non small cell lung cancer ( NSCLC ) . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ In the presence of Tax , both Cdk 4 and Cdk 6 were activated . ^^^ 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 . ^^^ These data suggest that Tax induces Cdk 4 and Cdk 6 activity in primary human T lymphocytes ; this Cdk activation is likely to account for the mitogenic Tax effect and for the abnormal T cell proliferation of HTLV 1 infected lymphocytes . . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ Substitution of two valine residues corresponding to amino acids 95 and 96 ( V95A and V96A ) of the p 16 peptide reduces the binding to cdk 4 and cdk 6 and increases its IC0 . 5 for kinase inhibition approximately threefold when linked to the Antennapedia homeodomain carrier sequence . ^^^ Substitution of aspartic acid 92 by alanine instead increases the binding of the peptide to cdk 4 and cdk 6 and the kinase inhibitory activity . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
There was no evidence for involvement of CDK 4 or CDK 6 in the blockade . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
D type CDKs , CDK 4 , and CDK 6 , phosphorylate retinoblastoma protein and are believed to regulate through the G 1 phase of the cell cycle . ^^^ CDK inhibitor p16INK4A has been characterized as binding CDK 4 and CDK 6 and as inhibiting phosphorylation of retinoblastoma protein by these CDKs . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The p18INK4c protein , a member of the p16 / INK4 cyclin dependent kinase ( CDK ) inhibitor family , is induced more than 50 fold during myogenic differentiation of mouse C2C12 myoblasts to become the predominant CDK inhibitor complexed with CDK 4 and CDK 6 in terminally differentiated myotubes . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The INK4a ARF locus encodes two unrelated proteins that both function in tumor suppression . p16INK4 binds to and inhibits the activity of CDK 4 and CDK 6 , and ARF arrests the cell cycle in a p 53 dependent manner . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Immunoprecipitation experiments revealed that p27Kip1 protein associates with Cdk 2 and Cdk 4 , but not with Cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In the studies analyzing cell cycle regulatory molecules , silymarin treatment of cells also resulted in a significant induction of cyclin dependent kinase inhibitors ( CDKIs ) Cip1 / p21 and Kip1 / p27 , concomitant with a significant decrease in CDK 4 expression , but no change in the levels of CDK 2 and CDK 6 and their associated cyclins E and D 1 , respectively . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Kinase activities of cdk 4 and cdk 6 were identified to be downregulated by sho saiko to . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The p 21 and p 27 have certain homology and can inhibit the activity of multiple CDKs ; p 16 and p 15 have higher homology and can specifically combine with CDK 4 and CDK 6 ; and the combination specificity of CDI 1 needs further research . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
ET also stimulated the activation of the cyclin dependent kinases Cdk 2 , Cdk 4 , and Cdk 6 , directed against the retinoblastoma protein pRb , and this was inhibited by as much as 80 % by ANP . ^^^
Interacting proteins: Q00534 and P11802	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 ) . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Here , we demonstrate that Cdc 2 cyclin B complex phosphorylates Ser 411 in the KIRSPRR sequence , whereas other Cdk cyclin complexes including those containing Cdk 2 , Cdk 4 , or Cdk 6 do not . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Both drugs inhibit cyclin dependent kinase 1 ( cdk 1 ) and cdk 2 ( required for cell cycle progression into the late G1 / S phase ) and cdk 5 ( inactive in cycling cells ) but not cdk 4 or cdk 6 ( active at early G 1 ) . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
These neuroblastoma cell lines express both CDK 4 and CDK 6 mRNA and protein , but only significant CDK 6 protein kinase activity was detected in this study . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^ Both Cdk 2 and Cdk 6 associated kinase activites are increased in the resistant sublines , but not Cdk 4 kinase activity . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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 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: Q00534 and P11802	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 ) . ^^^ P 16 ( MTS 1 ) , an inhibitor of cdk 4 and cdk 6 , resides within the deleted 9p21 region in these tumors . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Compared with their expression in sham operated controls ( SH ) , expression of cyclins D 2 and D 3 and of CDK 4 and CDK 6 increased significantly from day 3 to day 21 after AC concomitant with increased LV mass . ^^^ In vitro kinase activities of CDK 4 and CDK 6 increased approximately 70 % from day 7 to day 14 in AC myocytes compared with SH myocytes ( P < 0 . 03 ) . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The product of the alpha transcript , p 16 ( INK4a ) , is a recognized tumour suppressor that induces a G 1 cell cycle arrest by inhibiting the phosphorylation of the retinoblastoma protein by the cyclin dependent kinases , CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
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 . ^^^ In contrast , p16Ink4a , which binds monomeric CDK 4 and CDK 6 thereby preventing their binding to cyclin D , is increased dramatically at the time of senescence and remains high for at least 2 mo . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ While the activities of CDK 6 , CDK 2 and cdc 2 decreased markedly , the activity of CDK 4 did not change from the fetal period to the adult period . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The four members of the INK 4 gene family , p 16 ( INK4a ) , p 15 ( INK4b ) , p 18 ( INK4c ) and p 19 ( INK4d ) , are known to bind to and inhibit the closely related cyclin dependent kinases CDK 4 and CDK 6 as part of the regulation of the G1 / S transition in the cell division cycle . ^^^ A possible mode of binding between p 19 ( INK4d ) and CDK 4 and CDK 6 could therefore involve the loop segments of p 19 ( INK4d ) . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
INK4a , a critical element of the retinoblastoma gene pathway , binds to and inhibits the activities of CDK 4 and CDK 6 , while ARF , a critical element of the p 53 pathway , increases the level of functional p 53 via interaction with MDM 2 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Herein we show that RA induced LCL accumulation in the G0 / G1 phases correlated with the loss of the catalytic activity of all three G 1 associated CDKs ( CDK 2 , CDK 4 and CDK 6 ) and with increased levels of underphosphorylated pRb and , in some LCLs , p 130 . ^^^ 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 . ^^^ Overall , these results demonstrate that RA treatment of EBV immortalized B lymphocytes is associated with multiple effects on G 1 regulatory proteins , including p27Kip1 up regulation , decreased levels of cyclins D 2 , D 3 and A , and inhibition of CDK 2 , CDK 4 and CDK 6 activity , which ultimately result in reduced pRb phosphorylation and G0 / G1 growth arrest . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : The four members of the INK 4 gene family ( p 16 ( INK4a ) , p 15 ( INK4b ) , p 18 ( INK4c ) and p 19 ( INK4d ) ) inhibit the closely related cyclin dependent kinases CDK 4 and CDK 6 as part of the regulation of the G 1 > S transition in the cell division cycle . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : D type cyclins , in association with the cyclin dependent kinases CDK 4 and CDK 6 , promote progression through the G 1 phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
No mutations to the p 16 binding site of CDK 4 and CDK 6 nor any mutations to the coding region of p 16 itself were identified in neuroblastoma cell lines . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Members of the INK 4 family of cyclin dependent kinase ( CDK ) inhibitors specifically bind and inhibit the G 1 specific CDK molecules CDK 4 and CDK 6 . ^^^ The effects of these mutations on the ability of p 18 to bind and inhibit CDK 4 and CDK 6 or to inhibit cell growth were determined . ^^^ Our results indicate that the third ankyrin repeat and the NH 2 terminal portion of the fourth repeat constitute the essential element necessary for the ability of p 18 to bind and inhibit CDK 4 and CDK 6 . ^^^ Apart from this core interaction element , p 18 seems to use additional , distinct residues to differentially bind and inhibit CDK 4 and CDK 6 , accounting for the known penchant of p 18 to preferentially interact with CDK6 . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In mammals Cdk 4 ( or Cdk 6 in some cell types ) is required for starting the cell cycle . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The growth inhibition of OVCA 420 cells by mAb C 225 or 4D5 was associated with an increased G 1 cell population ; an increased level of a cyclin dependent kinase ( CDK ) inhibitor p27Kip1 with increased association of p27kip1 with CDK 2 , CDK 4 and CDK 6 ; and decreased activities of these CDKs . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The D type cyclins and their major kinase partners CDK 4 and CDK 6 regulate G 0 G1 S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product , pRB . ^^^ Here we show that although all four INK 4 proteins associate with CDK 4 and CDK 6 in vitro , only p 16 ( INK4a ) can form stable , binary complexes with both CDK 4 and CDK 6 in proliferating cells . ^^^ The other INK 4 family members form stable complexes with CDK 6 but associate only transiently with CDK 4 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
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: Q00534 and P11802	Pubmed	SVM Score :0.0
The concomitant high expression of the oncogenic protein CDK 4 ( and of CDK 6 ) , we observed , may amplify the leukemic advantage of prolonged lifespan blast cells by favoring cell progression through G 1 phase . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
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: Q00534 and P11802	Pubmed	SVM Score :0.0
Following IL 6 treatment of LNCaP , Western blot analysis showed that the protein levels of cyclin dependent kinase 2 ( CDK 2 ) , CDK 4 , and CDK 6 were decreased , while accumulation of CDK inhibitor p 27 ( Kip 1 ) was rapidly and markedly induced . ^^^ In vitro kinase assays revealed that the CDK associated histone H 1 and CDK 4 and CDK 6 associated pRb kinase activities were significantly inhibited in IL 6 treated LNCaP . ^^^ Further , a significant amount of p 27 ( Kip 1 ) was co precipitated with CDK 2 , CDK 4 and CDK 6 , as detected in immunoprecipitation experiments . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
CDK 4 activity was elevated in only 3 of 7 tumor samples ( range 40 160 % ) relative to control samples from the same patients , whereas a significant increase in CDK 6 activity was observed in the same group ( p < 0 . 05 ) . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
A cdk 2 inhibitor , Olomoucine , as well as a dominant negative cdk 2 construct prevented HLA class 1 mediated inactivation of Rb ; in contrast , dominant negative cdk 4 and cdk 6 constructs had no effect . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
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: Q00534 and P11802	Pubmed	SVM Score :0.0
In vitro binding experiments established that the P48L mutant protein does not bind to cdk 4 or cdk 6 and thus is functionally abnormal . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
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: Q00534 and P11802	Pubmed	SVM Score :0.0
The p 16 protein associates exclusively with Cdk 4 and Cdk 6 , inhibiting their complexation with D type cyclins and the consequent phosphorylation of pRb . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
This diminution of function was independent of CDK 4 and CDK 6 binding ability . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
These include mutation and / or deletion of the retinoblastoma ( RB 1 ) gene , homozygous deletion of the CDKN2A and CDKN2B genes , as well as amplification and overexpression of the CDK 4 and CDK 6 genes . ^^^ 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: Q00534 and P11802	Pubmed	SVM Score :0.0
The dissociation of p 21 ( CIP 1 ) and p 27 ( KIP 1 ) from their cdk complexes correlated well with the activation of cdk 2 , cdk 4 , and cdk 6 and the release from cell cycle arrest . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
CDK 4 , CDK 6 , cyclins D 3 and E and , to a minor extent , CDK 2 failed to accumulate at the protein level after mitogenic stimulation in the presence of UV MV . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
In order to address the potential relationship of MCT 1 to cell cycle regulatory molecules , we analyzed the ability of MCT 1 overexpression to modulate cdk 4 and cdk 6 kinase activity in NIH3T3 fibroblasts constitutively overexpressing MCT 1 . ^^^ We observed an increase in the kinase activity of both cdk 4 and cdk 6 in asynchronously growing transformed cells compared with the parent cells . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ Furthermore , cdk 2 , cdk 4 , and cdk 6 kinase activities remain unaffected after CPT treatment . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ We report here the production and characterization of a series of 12 monoclonal antibodies ( MAbs ) that specifically recognize either Cdk 4 or Cdk 6 . ^^^ 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: Q00534 and P11802	Pubmed	SVM Score :0.0
Among the 17 sequence variants analysed , three distinct categories can be distinguished : those that abrogate the binding of p16INK4a to CDK 4 and CDK 6 , those that alter the properties of the protein without preventing it from interacting with CDKs , and those that have no discernible effect on protein function . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
There was no effect on p 21 ( Cip 1 ) , cyclin D 2 , cdk 4 , and cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Deregulated activity of cdk 4 or cdk 6 can lead to inappropriate cellular proliferation and tumorigenesis accompanied by unchecked inactivation of the retinoblastoma tumor suppressor protein . ^^^ Certain tumor types preferentially activate either cdk 4 or cdk 6 , suggesting that these kinases may not be equivalently oncogenic in all cell types . ^^^ Although it is clear that cdk 4 can act as an oncogene at least in part by evading inhibition by p 16 ( INK4a ) , the role of cdk 6 in tumorigenesis is less well understood . ^^^
Interacting proteins: Q00534 and P11802	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 ) . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
However , when stimulated with serum containing oncogenic growth factors , they come to rely on either Cdk 4 or Cdk 6 , and their S phase entry can not be blocked unless both Cdk 4 and Cdk 6 are immunodepleted . ^^^ However , both Cdk 4 and Cdk 6 are activated upon serum stimulation , and neither the amounts of Cdk 6 , Cdk 4 , cyclin D 1 , and cyclin dependent kinase inhibitors nor the activities or subcellular localization of Cdk 6 and Cdk 4 are significantly influenced by oncogenic stimulation . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The p 16 ( INK4a ) tumor suppressor inhibits cyclin dependent kinases ( CDK 4 and CDK 6 ) . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The INK4A gene , a candidate tumor suppressor gene located on chromosome 9p21 , encodes two protein products , p 16 and p 19 ( ARF ) . p 16 is a negative cell cycle regulator capable of arresting cells in the G 1 phase by inhibiting cyclin dependent kinases 4 ( Cdk 4 ) and 6 ( Cdk 6 ) , thus preventing pRB phosphorylation . p 19 ( ARF ) prevents Mdm 2 mediated neutralization of p 53 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
We found that aging led to significant declines in the ability of mouse CD 4 ( + ) T cells to respond to CD 3 and CD 28 stimuli by induction of the cyclin dependent kinases CDK 2 , CDK 4 , and CDK 6 , whether the defect was assessed by protein level or functional activity . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The present study was undertaken to explore the expression and regulation of six additional members of the Cdk family ( Cdk 2 , Cdk 3 , Cdk 4 , Cdk 6 , Cdk 7 and Cdk 8 ) during lens differentiation . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ A different pattern of expression in the two models of hepatocyte proliferation , although less dramatic , was also observed for CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
UCN 01 did not inhibit the CDK 4 and CDK 6 activities in both cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The expressions of CDK 2 and CDK 6 were down regulated during G 1 block of HL 60 cells , and CDK 4 is progressively elevated . ^^^ Immunoprecipitation study demonstrated that p 27 did not bind to CDK 2 , CDK 4 and CDK 6 in EB 1089 treated HL 60 cell extracts . ^^^ In contrast , complexes immunoprecipitated from EB 1089 treated HL 60 cells with antibodies CDK 2 and CDK 6 contained higher amounts of immunodetectable p 21 protein compared to untreated HL 60 cells , whereas no detectable change was noted with anti CDK 4 antibody . ^^^ Furthermore , the kinase activities of CDK 2 and CDK 6 were decreased while little change was observed in CDK 4 activity . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
However , an increase in the expression of the Cdk4 / 6 inhibitor p 18 ( INK4c ) and its extensive association with Cdk 4 and Cdk 6 were apparent following progestin treatment . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Cellular response to oncogenic ras involves induction of the Cdk 4 and Cdk 6 inhibitor p 15 ( INK4b ) . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
We report that the INK 4 proteins share the ability to arrest cells in G 1 , and interact with CDK 4 or CDK 6 with similar avidity . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
While the catalytic activity of all 3 G ( 1 ) associated CDKs ( CDK 2 , CDK 4 and CDK 6 ) was strongly inhibited in RA treated LCLs , only CDK 2 associated kinase activity was reduced in DG 75 cells arrested in G ( 0 ) / G ( 1 ) by RA . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The consequent induction of immediate early response genes , such as cyclins , and subsequent activation of cyclin dependent kinases ( CDK 4 , CDK 6 and CDK 2 ) inactivates the retinoblastoma family of proteins ( pRb , p 107 and p 130 , together termed pocket proteins ) , and releases their suppressive association with E2F transcription factors . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Both p15INK4B and p15 . 5INK4B bound to CDK 4 and CDK 6 , inhibited DNA synthesis , and caused replicative senescence of a human glioma cell line . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Despite the significant amounts of CDK 4 and CDK 6 , only nonphosphorylated forms of retinoblastoma protein were detectable in fully luteinized cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Most commonly , such mutations involve CDKN2A , a cyclin dependent kinase inhibitor of two kinases , CDK 4 and CDK 6 , which phosphorylate the retinoblastoma protein ( pRB ) and thereby promote passage through the G1 / S cell cycle restriction point . ^^^ Despite the sequence and functional homology between CDK 4 and CDK 6 , the role of germline mutations in CDK 6 in melanoma predisposition is unknown . ^^^ We detected no CDK 6 mutations within the p 16 ( CDKN2A ) binding domain in index cases from 60 melanoma prone kindreds that lacked germline mutations in the coding regions of either CDKN2A or within the entire CDK 4 coding region . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
METHODS : Sixteen cancer associated p 16 mutant proteins , resulting from missense mutations , were characterized for their ability to bind and inhibit the cyclin dependent kinases ( CDK 4 and CDK 6 ) and to induce cell cycle arrest in G ( 1 ) phase . ^^^ Thus , p 16 mutant proteins that retain CDK 4 and CDK 6 binding may have more subtle functional defects . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Progression to senescence was accompanied by a progressive increase in both the level of p 16 ( INK4A ) and in its association with cdk 4 and cdk 6 . ^^^ As HPECs approached senescence , cdk 4 and cdk 6 bound p 16 ( INK4A ) showed a shift to a slower mobility due to a change in its phosphorylation profile . ^^^ As p 16 ( INK4A ) increased in cdk 4 and cdk 6 complexes , there was a loss of cyclin D 1 binding . ^^^ The altered phosphorylation of p 16 ( INK4A ) in senescent prostatic epithelial cells may facilitate its association with cdk 4 and cdk 6 and play a role in the inactivation of these kinases . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In the same cells , a decrease in the phosphorylated form of Rb protein and an increase in the p 130 protein were observed without changes in the protein level of cell cycle dependent kinase 2 ( Cdk 2 ) , Cdk 4 , and Cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Glucocorticoids induced a significant decrease in the percentage of cells in S phase and in CDK 1 , CDK 4 and CDK 6 expression and an increase in the percentage of cells in subG 1 peak . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
In contrast , we were not able to observe a similar effect on the kinase activity of either cdk 6 or cdk 2 , indicating that the phosphatase activity of calcineurin was specific for cdk 4 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Expression of p19INK4d , CDK 4 , CDK 6 in glioblastoma multiforme . ^^^ No gene rearrangement or deletion was observed in the p19INK4d gene in these cell lines ; however , expression of CDK 4 and CDK 6 was elevated relative to matched normal brain tissue in eight of 18 GBM tumours ( 44 % ) . ^^^ These data attest to the functional importance of both CDK 4 and CDK 6 in astrocytic tumourigenesis , particularly during the later stages of tumour progression . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
However , RA had no effect on the levels of cyclins A , D 1 , D 3 , E , or H , or on Cdk 2 , Cdk 4 , Cdk 5 , CDk 6 , Cdk 7 , p 16 ( Ink4A ) , p 15 ( Ink4B ) , p 53 , or pRb proteins in CH 27 cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
This phosphorylation is thought to contribute to the derepression of E2F responsive genes and to be mediated , in part , by Cdk 4 and Cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Both inhibitors were found in complex with CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
CDK 4 and CDK 6 , which are activated by D type cyclins during the G ( 1 ) phase of the cell cycle , are thought to be responsible for phosphorylation of the retinoblastoma gene product ( pRb ) . ^^^ The tumor suppressor p 16 ( INK4A ) inhibits phosphorylation of pRb by CDK 4 and CDK 6 and can thereby block cell cycle progression at the G ( 1 ) / S boundary . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Both p 21 ( Cip 1 ) and p 27 ( Kip 1 ) proteins were induced during erythroid differentiation , but only p 27 ( Kip 1 ) associated with the principal G ( 1 ) CDKs cdk 4 , cdk 6 , and cdk 2 . ^^^ The kinetics of binding of p 27 ( Kip 1 ) to CDK complexes was distinct in that p 27 ( Kip 1 ) associated primarily with cdk 4 ( and , to a lesser extent , cdk 6 ) early in differentiation , followed by subsequent association with cdk 2 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
In mammalian cells , Cdk 2 , Cdk 4 , Cdk 6 and associated cyclins control the G ( 1 ) to S phase transition . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The results also indicate that CDK 4 and CDK 6 are functionally distinct and support our hypothesis that the two CDKs regulate cell division at different stages of erythroid maturation . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The 113insArg mutant p 16 ( INK4a ) was unable to bind cdk 4 and cdk 6 in an in vitro binding assay . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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 ) . ^^^ Chemical modification resulted in the identification of PD 0183812 as a potent and highly selective inhibitor of both CDK 4 and CDK 6 kinase activity , which is competitive with ATP . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^ Analysis of normal B cell precursors by Western blotting indicated that CDK 4 , CDK 6 , p 19 ( INK4d ) , and p 57 ( KIP 2 ) were expressed , whereas p 16 ( INK4a ) was not detected . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Rb phosphorylation is mediated by cyclin dependent kinases ( CDKs ) , whose activity is enhanced by cyclins and inhibited by CDK inhibitors . p 16 ( INK4A ) is a member of a family of inhibitors specific for CDK 4 and CDK 6 . p 16 ( INK4A ) is deleted and inactivated in a wide variety of human malignancies , including familial melanomas and pancreatic carcinoma syndromes , indicating that it is an authentic human tumor suppressor . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
While members of the INK 4 family ( p16INK4A , p15INK4B , p18INK4C , p19INK4D ) interact specifically with CDK 4 and CDK 6 , the CIP / KIP inhibitors p21CIP1 / WAF1 , p27KIP1 and p57KIP2 inhibit a broader spectrum of CDK . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Therefore , testicular GCTs were analyzed as to the expression of CDK 2 , CDK 4 , CDK 6 , and the expression of their catalytic partners cyclins D 1 , D 2 and E by semiquantitative reverse transcription PCR . ^^^ 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 ) . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
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: Q00534 and P11802	Pubmed	SVM Score :0.0
Ras and Protein kinase C ( PKC ) ) , and cell cycle regulatory molecules ( e . g . mouse double minute 2 ( Mdm 2 ) , cyclin dependent kinase 4 ( CDK 4 ) , and CDK 6 ) , that positively regulate proliferation and cell cycle progression . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
In activated T cells , p 18 ( INK4c ) remained constant , and preferentially associated with and inhibited CDK 6 but not CDK 4 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Whilst CDK 2 and cdc 2 may be pivotal in the withdrawal of cardiac myocytes from the cell cycle , CDK 4 and CDK 6 may be critical for maintaining hypertrophic growth of the myocyte during development . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In contrast , ATRA strongly suppressed the pRb kinase activities of the cyclin dependent kinases ( Cdks ) Cdk 4 , Cdk 6 , and Cdk 2 . ^^^ ATRA did not influence the expressions of Cip / Kip family Cdk inhibitors or those of cyclins D 1 and D 2 , whereas it strongly inhibited the expressions of cyclins D 3 and E , Cdk 4 , Cdk 6 , and Cdk 2 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Inactivation of the tumor suppressor gene p 16 ( INK4a / CDKN2 ) , a specific inhibitor of the cyclin dependent kinases CDK 4 and CDK 6 , is the most common genetic alteration in human pancreatic cancer , making it an ideal target for gene replacement . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Additionally , VEGI treatment led to inhibition of the activities of cyclin dependent kinases CDK 2 , CDK 4 , and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Also , RA treatment increased expression of the cdk inhibitor p 27 and decreased activity of cdk 2 , cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
This phenomenon shows an increased expression of growth cell inhibitors : p21Waf1 described as an universal CDK inhibitor and p16INK4a as a specific inhibitor for both G 1 phase kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Both cyclins were associated with cdk 4 but not with cdk 6 , which is the catalytic partner of D type cyclins in normal B cells . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Tax stimulates the cell cycle in the G ( 1 ) phase by activating the cyclin dependent kinase ( CDK ) CDK 4 and CDK 6 holoenzyme complexes . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
To avoid the confounding pleiotropic effects of HPVE 7 frequently used in such studies , here we have employed retroviral vectors over expressing CDK 4 or CDK 6 as a more representative model of naturally occurring mutations targeting the Rb pathway . ^^^ Surprisingly however , this could not explain arrest , since expression of mutant CDK 4 and / or CDK 6 , incapable of binding p 16 ( Ink4a ) , did not confer any greater lifespan extension than the wild type CDKs . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Cyclin D 3 bound to both cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The amounts of cdk 4 , cdk 6 , and the D type cyclins are not affected by 18 h of hypoxia . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Significant down regulation of expression in patients was detected in genes CDK 4 inhibitor A , PURA , notch 1 in mononuclears ; STAT 2 , STAT 5 , RAR alpha , MCL 1 , junB , caspase 4 in granulocytes ; CDK 6 , GADD 153 , ERBB 3 , cadherin 5 in both fractions . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Biochemical studies in mouse epidermis showed that cdk 6 activity increased twofold in cdk 4 deficient mice compared to wild type siblings . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Structural analysis of the inhibition of Cdk 4 and Cdk 6 by p 16 ( INK4a ) through molecular dynamics simulations . ^^^ In order to get some insight into the key interactions governing recognition between different cyclin dependent kinases and the p 16 ( INK4a ) tumor suppressor , the present work reports the results of molecular dynamics simulations of both , the Cdk 6 p16 ( INK4a ) complex and the Cdk 4 p16 ( INK4a ) complex , respectively at 300 K . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
On the other hand , cycling Cdks such as Cdk 2 , Cdk 4 and Cdk 6 , initiate death pathways by derepressing E2F 1 / Rb dependent transcription at the neuronal G1 / S checkpoint . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The kinase activity of cdk 2 , cdk 4 , and cdk 6 was significantly reduced and hypophosphorylation of pRb on serine 795 ( S 795 ) and threonine 373 ( T 373 ) was observed . ^^^ 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 . ^^^ TGFbeta 1 induced growth arrest was associated with notably increased binding of p 21 ( WAF 1 ) to cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ In addition , monensin markedly enhanced the binding of p 27 with CDK 2 , CDK 4 and CDK 6 . ^^^ Furthermore , the activities of CDK 2 , CDK 4 and CDK 6 associated kinase were reduced in association with hypophosphorylation of Rb protein . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^ We recently found two novel functions for Cdk 6 executed in fibroblasts although unlike Cdk 4 it is dispensable for their proliferation . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Molecular expression of the Cdk inhibitors p 16 or p 27 , or of dominant negative Cdk 2 , Cdk 4 , or Cdk 6 was also protective against lactacystin induced death . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ The enzymatic activities of cyclins D 1 , E , A , Cdk 1 , Cdk 4 , Cdk 6 , Cdk 7 , and Wee 1 were measured using in vitro kinase assays . ^^^ 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 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ Furthermore , the activities of CDK 2 , CDK 4 and CDK 6 associated kinase were reduced and the lack of the CDK activity was paralleled by increased hypophosphorylation of Rb protein . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
We found that CDK 6 ( but not CDK 4 ) is rapidly downregulated as MEL cells are induced to re enter erythroid differentiation and that maintenance of CDK 6 ( but not CDK 4 ) activity by transfection blocks differentiation . ^^^ Our findings suggest that studying the relative roles of CDK 6 and CDK 4 in other types of malignant cells will be important in designing approaches for cell cycle inhibition and differentiation therapy in cancer . . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
These multipolar tissue culture astrocytes were infected with viruses expressing either cdk 4 or cdk 6 . ^^^ Several other differences in cdk 4 and cdk 6 infected cells were noted , including differential binding to a subset of cell cycle inhibitor proteins and a distinct pattern of subcellular localization of these kinases . ^^^ Together , these data indicate several important differences between cdk 4 and cdk 6 that highlight unique functional roles for these cyclin dependent kinases . . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Contrarily to CDK 6 , the level of CDK 4 , the other kinase involved in the G ( 1 ) phase of the cell cycle , remains unchanged . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
CDK 2 , CDK 4 , CDK 6 and their associated cyclins control the G 1 to S phase transition . ^^^ The association of CDK 4 or CDK 6 with D type cyclins is critical for G 1 phase progression , whereas the CDK 2 cyclin E complex is important for initiation of the S phase . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The protein levels of cdk 2 , cdk 4 , and cdk 6 were not altered in HL60AR cells , whereas the activities of both ckd 2 and cdk 6 were higher in AR than in PT cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Temporal distribution of CDK 4 , CDK 6 , D type cyclins , and p 27 in developing mouse oocytes . ^^^ This study seeks to initiate analyses of the potential oocyte specific functions of regulators of G1 / S progression CDK 4 , CDK 6 , D type cyclins , and p 27 by first determining their expression patterns in growing and maturing mouse oocytes and in mouse embryos early after fertilization . ^^^ 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: Q00534 and P11802	Pubmed	SVM Score :0.0
D type cyclins interact with CDK 4 and CDK 6 to drive the progression of a cell through early / mid G ( 1 ) in response to mitogen stimulation . ^^^ 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: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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 . ^^^ 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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
End stage differentiation of neutrophil granulocytes in vivo is accompanied by up regulation of p27kip1 and down regulation of CDK 2 , CDK 4 , and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Wild type p16INK4a suppresses cell growth , telomerase activity and DNA repair in human breast cancer MCF 7 cells . p16INK4a , a cell cycle inhibitor that inhibits cyclin dependent kinase 4 ( cdk 4 ) and cdk 6 , has been found as the tumor suppressor gene and is frequently deleted , methylated or mutated in many malignancies . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Mammalian cells cycle without the D type cyclin dependent kinases Cdk 4 and Cdk 6 . ^^^ Cdk 4 and Cdk 6 are thought to be essential for initiation of the cell cycle in response to mitogenic stimuli . ^^^ Previous studies have shown that Cdk 4 is dispensable for proliferation in most cell types , an observation attributed to a putative compensatory role by Cdk 6 . ^^^ Embryos defective for Cdk 4 and Cdk 6 die during the late stages of embryonic development due to severe anemia . ^^^ In vitro , embryonic fibroblasts lacking Cdk 4 and Cdk 6 proliferate and become immortal upon serial passage . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Moreover , ZD 1839 increased the protein levels of p 27 ( KIP 1 ) and retinoblastoma related Rb2 / p130 while decreased the expression of cyclin dependent kinase 2 ( CDK 2 ) , CDK 4 , CDK 6 and cyclin D 1 , cyclin D 3 . ^^^ Our results indicate that downregulation of the expression and function of CDK 2 , CDK 4 , CDK 6 , cyclin D 1 and cyclin D 3 , as well as upregulation of p 27 ( KIP 1 ) and pRb2 / p130 , are strong candidates for the cell cycle regulator that arrests ZD 1839 treated A 549 cells at G 1 phase . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The CDKN2A gene , located on chromosome 9p21 , encodes the tumour suppressor protein , p16INK4A , which decelerates the cell cycle by inactivating CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ All cell lines expressed Cdk 4 and Cdk 6 protein . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The p16INK4a tumor suppressor protein functions as an inhibitor of CDK 4 and CDK 6 , the D type cyclin dependent kinases that initiate the phosphorylation of the retinoblastoma tumor suppressor protein , RB . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
PD 0332991 is a highly specific inhibitor of cyclin dependent kinase 4 ( Cdk 4 ) ( IC 50 , 0 . 011 micromol / L ) and Cdk 6 ( IC 50 , 0 . 016 micromol / L ) , having no activity against a panel of 36 additional protein kinases . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
We show that all RINGO family members can bind to and activate CDK 1 and CDK 2 , albeit with different efficiencies , but they do not bind to CDK 4 or CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
ATRA inhibited the mRNA expression of CDK 6 , CDK 4 , cyclinD 3 and cyclinD 1 . ^^^ ATRA and sodium butyrate inhibited the mRNA expression of CDK 6 , CDK 4 , CDK 2 , cyclinD 1 , cyclinD 2 and cyclinD 3 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Of particular importance is our finding that CIP did not inhibit endogenous or transfected p35 / Cdk5 activity , nor did it inhibit the other cyclin dependent kinases such as Cdc 2 , Cdk 2 , Cdk 4 and Cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
G 1 arrest was associated with an increase in Cip1 / p21 and a decrease in CDK 2 , CDK 4 and CDK 6 protein levels . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
To that end , we examined the expression of p18INK4C by immunohistochemistry in various liver diseases , including 51 HCCs , and also studied the relationship between p18INK4C expression , the phosphorylation of retinoblastoma protein ( pRb ) , and the activity level of Cdk 4 and Cdk 6 . ^^^ In p18INK4C positive HCCs , p18INK4C dominantly interacted with Cdk 4 rather than with Cdk 6 . pRb phosphorylated at serine ( Ser ) 780 was detected more frequently in p18INK4C negative than in p18INK4C positive HCCs . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Functionally , co immunoprecipitation assays using antibodies against cdk 4 and / or cdk 6 revealed that only the two most acidic p 16 variants associated with cdk4 / 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The most well understood function of the D type cyclins is to activate the G ( 1 ) kinases , cdk 4 and cdk 6 , and target the retinoblastoma gene product ( pRb ) for phosphorylation and inactivation . pRb can suppress S phase entry , cause a transient G ( 1 ) arrest following DNA damage , and is critical in establishing terminal cell cycle withdrawal in cells exposed to differentiation or senescence inducing signals . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The cyclin dependent kinases ( CDK ) CDK 1 , CDK 2 , CDK 4 , and CDK 6 are serine / threonine protein kinases targeted in cancer therapy due to their role in cell cycle progression . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
CDK 4 and CDK 6 form a subfamily among the CDKs in mammalian cells , as defined by sequence similarities . ^^^ Compared to CDK 2 and CDK 5 , structural information on CDK 4 and CDK 6 is sparse . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
In pull down assays GST Puralpha efficiently binds Cdk 2 and Cdk 1 , binds Cdk 4 less efficiently , and does not display binding to Cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ However , recent analyses of mice lacking D cyclins , or CDK 4 and CDK 6 reveal that these proteins are critically required for proliferation only in the selected cell types . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Indeed , this phosphorylation was observed 6 hours after p 25 induction and was abolished in the presence of a Cdk 5 inhibitor , roscovitine , which does not inhibit the usual Rb cyclin D kinases Cdk 4 and Cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	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 . ^^^ We showed predominant overexpression of CCND 2 and CDK 4 compared to CCND1 / D3 and CDK 6 respectively . ^^^ We found a specific correlation between relapse and CDK 4 overexpression , but not CDK 6 overexpression . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
In contrast , cyclins D 2 and D 3 predominated in fetal liver and were complexed with both CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Preferences for phosphorylation sites in the retinoblastoma protein of D type cyclin dependent kinases , Cdk 4 and Cdk 6 , in vitro . ^^^ D type cyclin dependent kinases ( Cdk 4 and Cdk 6 ) regulate the G 1 to S phase progression of the mammalian cell cycle . ^^^ It has been suggested that Cdk 4 and Cdk 6 may have distinct functions in vivo , even though they are indistinguishable biochemically . ^^^ Here we show that although these Cdks phosphorylate multiple residues in pRB , they do so with different residue selectivities in vitro ; Thr 821 and Thr 826 are preferentially phosphorylated by Cdk 6 and Cdk 4 , respectively . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Among them , compound 20 displayed high inhibitory potency at CDK 1 ( IC ( 50 ) = 0 . 021 microM ) , CDK 2 , and CDK 5 and submicromolar potency at CDK 4 , CDK 6 , and CDK 7 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Recent genetic evidence obtained with gene targeted mice has shown that Cdk 4 and Cdk 6 are not needed for entry into the cell cycle after mitogenic stimuli and organogenesis ; however , they are essential for the proliferation of some endocrine and hematopoietic cells . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Since exit from the cell cycle is a necessary step in terminal differentiation , down regulation of a mitogenic factor may be expected in this process , however it is surprising that this association has not been previously uncovered and that it is apparently not shared with cdk 4 , long understood to be a functional homolog of cdk 6 . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
First , Hoxa 10 deficiency results in the aberrant region specific expression of cyclin dependent kinase 4 ( cdk 4 ) and 6 ( cdk 6 ) , growth differentiation factor 10 ( Gdf 10 ) , hepatocyte growth factor ( Hgf ) and Snail 2 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
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 ) . ^^^ By contrast , cyclin D 2 and cdk 6 are coordinately increased , thereby overriding the inhibition by cdk inhibitors p 18 ( INK4c ) and p 27 ( Kip 1 ) and phosphorylating Rb in conjunction with the existing cdk 4 . ^^^ Thus , cyclin D 1 pairs exclusively with cdk 4 and cdk 6 pairs only with cyclin D 2 , although cyclin D 2 can also pair with cdk 4 in multiple myeloma cells . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
The berberine induced inhibition of proliferation of DU 145 , PC 3 , and LNCaP cells was associated with G 1 phase arrest , which in DU 145 cells was associated with inhibition of expression of cyclins D 1 , D 2 , and E and cyclin dependent kinase ( Cdk ) 2 , Cdk 4 , and Cdk 6 proteins , increased expression of the Cdk inhibitory proteins ( Cip1 / p21 and Kip1 / p27 ) , and enhanced binding of Cdk inhibitors to Cdk . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
The encoded protein arrests cell cycle in G 1 phase by binding to CDK 4 and CDK 6 , inhibiting their kinase function . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Cells exposed to 17 AAG and ZD 1839 displayed a significant reduction in cell cycle regulatory proteins , such as CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
Our western blot analysis showed that berberine induced G ( 1 ) cell cycle arrest was mediated through the increased expression of Cdki proteins ( Cip1 / p21 and Kip1 / p27 ) , a simultaneous decrease in Cdk 2 , Cdk 4 , Cdk 6 and cyclins D 1 , D 2 and E and enhanced binding of Cdki Cdk . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
Within cyclin D 3 complexes , T loop phosphorylation of CDK 4 , but not of CDK 6 , was directly regulated , identifying it as a determining target for cell cycle control by extracellular factors . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
CDK 4 and CDK 6 , however , may be at least as important as enzymes for cell cycle regulation and could provide alternative treatment options . ^^^
Interacting proteins: Q00534 and P11802	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: Q00534 and P11802	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: Q00534 and P11802	Pubmed	SVM Score :0.0
For instance , they have illustrated that Cdk 4 and Cdk 6 are not essential for cell division during embryonic development except in the hematopoietic system . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
MG 132 caused a significant increase in p 21 and p 27 protein and decrease in CDK 2 , but no change in p 53 , p 57 , CDK 4 , or CDK 6 protein . ^^^
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P11802	Pubmed	SVM Score :0.0
NA