Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.94988337
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 . 0.94988337^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.64690188
These results suggest : ( a ) the involvement of P16INK4 in glioma progression ; ( b ) that mechanisms other than mutation or deletion can down regulate expression of the p16 / CDKN2 gene ; and ( c ) that the balance between CDK 4 and its cognate inhibitor , P16INK4 , may confer a cell growth advantage and facilitate tumor progression . . 0.64690188^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.59053345
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 . 0.59053345^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.51136019
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 . 0.51136019^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.59881952
Analysis of p16INK4a and its interaction with CDK 4 . 0.59881952^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.57925374
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 . 0.57925374^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.54141898
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 . 0.54141898^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.545559
Surprisingly , using two different mutants we show that CDK 4 ' s ability to bind to p16INK4a and not its kinase activity is important for its transforming potential . 0.545559^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.59117307
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 . 0.59117307^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.79427541
EPC 2 hTERT cells overcame senescence and were immortalized without p16INK4a genetic or epigenetic alterations . p16INK4a was expressed at moderate levels and remained functional as evidenced by induction with UV treatment and binding to cyclin dependent kinase 4 and 6 . 0.79427541^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Loss of p16INK4a expression would disrupt the retinoblastoma ( Rb ) / p16INK4a / cyclin D dependent kinase ( CDK 4 ) pathway , whereas loss of p14ARF expression would inactivate both the Rb and p53 / MDM2 / p14ARF pathways through MDM 2 , which can complex with either Rb or p 53 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Individuals with presumably hereditary uveal melanoma do not harbour germline mutations in the coding regions of either the P16INK4A , P14ARF or cdk 4 genes . ^^^ We hypothesized that germline mutations in the p16INK4A , p14ARF or CDK 4 genes might contribute to some cases of familial UMM , or to some cases of UMM associated with another melanoma . ^^^ We screened by polymerase chain reaction single strand conformation polymorphism the entire coding sequence of the INK4A ARF locus ( exon 1alpha from p16INK4A , exon 1beta from p14ARF , and exons 2 and 3 , common to both genes ) , as well as the exons 2 , 5 and 8 of the CDK 4 gene , coding for the functional domains involved in p 16 and / or cyclin D 1 binding . ^^^ A previously reported polymorphism in exon 3 of the INK4A ARF locus was found in one patient affected with bilateral UMM , but no germline mutations were detected , either in the p16INK4A , p14ARF or CDK 4 genes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutational analysis of N ras , p 53 , p16INK4a , p14ARF and CDK 4 genes in primary human malignant mesotheliomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In Ewing cell lines , cyclin D 1 , CDK 4 , Rb , p27KIP1 and c Myc were consistently highly expressed whereas p57KIP2 , p15INK4B and p14ARF demonstrated undetectable or low expression levels . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The INK4a ARF locus , localized on 9p21 , encodes two tumor suppressor proteins , p16INK4a and p14ARF , acting respectively through the CDK 4 pRb and the p 53 pathways . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Analysis of mRNA and protein levels in melanomas with 12q14 amplification demonstrated overexpression of target genes CDK 4 and MDM 2 without loss of CDKN2A P 16 ( P16INK4A ) or CDKN2A P14ARF ( P14ARF ) expression , important regulators of the RB 1 and TP 53 pathways , which are commonly lost or mutated in melanoma . ^^^ These results suggest that coamplification of CDK 4 and MDM 2 may substitute for loss of P16INK4A and P14ARF function in a subset of melanomas . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Prevalence of germ line mutations in p 16 , p19ARF , and CDK 4 in familial melanoma : analysis of a clinic based population . ^^^ We screened for germ line mutations in p 16 and in two other candidate melanoma genes , p19ARF and CDK 4 , in 33 consecutive patients treated for melanoma ; these patients had at least one affected first or second degree relative ( 28 independent families ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Cells arrested in G 1 by ectopically expressed p19ARF contained considerably reduced G 1 cyclin dependent kinase ( cdk 2 and cdk 4 ) activities . ^^^ 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: Q8N726 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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p16 / multiple tumor suppressor ( MTS ) 1 / inhibitor of CDK 4 ( INK 4 ) a / CDKN2 gene , a CDKI , is frequently deleted in a variety of human cancers . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Moreover , employing the human native partially purified p 16 ( INK 4 ) or the pure recombinant protein , we have been able to demonstrate in vitro the dissociation of CDK 4 cyclin D 1 complex and the formation of CDK 4 p16 ( INK 4 ) bimolecular complex . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 inhibitor genes ( INK 4 ) regulate the cell cycle and are candidate tumor suppressor genes . ^^^
Interacting proteins: Q8N726 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: Q8N726 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 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Members of the INK 4 protein family specifically inhibit cyclin dependent kinase 4 ( cdk 4 ) and cdk 6 mediated phosphorylation of the retinoblastoma susceptibility gene product ( Rb ) . p16INK4A , a prototypic INK 4 protein , has been identified as a tumor suppressor in many human cancers . ^^^
Interacting proteins: Q8N726 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 . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
We show that Sindbis virus induced expression of CKIs p 16 ( ink 4 ) , p 21 ( waf / cip1 ) , and p 27 ( kip 1 ) , as well as DN Cdk 4 and 6 , but not DN Cdk 2 or 3 , protect sympathetic neurons against UV irradiation and AraC induced death . ^^^
Interacting proteins: Q8N726 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: Q8N726 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 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Since the structures of several ankyrin repeat proteins including the INK 4 ( inhibitor of cyclin dependent kinase 4 ) family have been reported recently , the detailed structures and the functional roles of the loops have drawn considerable interest . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Components of the pRb pathway which are often altered in tumour progression include the INK 4 cyclin dependent kinase ( CDK ) inhibitors p16INK4a / CDKN2A and p15INK4b / CDKN2B , CDK 4 , D type cyclins and pRb . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Here we report that a family of proteins containing ankyrin repeats , the inhibitors of Cdk 4 ( INK 4 ) is able to bind NF kappaBp 65 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The INK 4 ( inhibitor of cyclin dependent kinase 4 ) family consists of four tumor suppressor proteins : p 15 ( INK4B ) , p 16 ( INK4A ) , p 18 ( INK4C ) , and p 19 ( INK4D ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Here we present evidence that activation of a cAMP pathway correlates with multiple cellular changes in these cells : ( 1 ) increased expression of the transcription factor microphthalmia ; ( 2 ) increased melanogenesis ; ( 3 ) increased association of the cyclin dependent kinase inhibitors ( CDK Is ) p 27 ( KIP 1 ) and p 16 ( INK 4 ) with CDK 2 and CDK 4 , respectively ; ( 4 ) failure to phosphorylate the retinoblastoma protein ( pRB ) ; ( 5 ) decreased expression of E2F1 , E2F2 , and E2F4 proteins ; ( 6 ) loss of E2F DNA binding activity ; and ( 7 ) phenotypic changes characteristic of senescent cells . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Taken together , it is suggested that p 21 and cyclin D 1 act cooperatively as activators of Cdk 4 through the release of CKIs of the INK 4 family . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Tumor suppressor INK 4 : quantitative structure function analyses of p18INK4C as an inhibitor of cyclin dependent kinase 4 . ^^^
Interacting proteins: Q8N726 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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
We hypothesized that a variation in the inactivation of cdk 2 and cdk 4 during the G ( 1 ) phase of the cell cycle by p 27 ( Kip 1 ) , p 21 ( Cip 1 ) , and p 16 ( Ink 4 ) leads to different effects on VSMC growth in vitro and in vivo . ^^^ METHODS AND RESULTS : The expression of p 27 ( Kip 1 ) and p 21 ( Cip 1 ) in serum stimulated VSMCs inactivated cdk 2 and cdk 4 , leading to G ( 1 ) growth arrest . p 16 ( Ink 4 ) inhibited cdk 4 , but not cdk 2 , kinase activity , producing partial inhibition of VSMC growth in vitro . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Within the INK 4 family , this regulatory mode appears restricted to p19INK4d whose ubiquitination was dependent on the integrity of lysine 62 , and binding to CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Within the tumor suppressor protein INK 4 ( inhibitor of cyclin dependent kinase 4 ) family , p15INK4B is the smallest and the only one whose structure has not been determined previously , probably due to the protein ' s conformational flexibility and instability . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Frequent deletions or mutations of the INK 4 gene , which encodes the cyclin dependent kinase 4 inhibitor p16INK4a , have been documented in various human cancers , but little is known about the role of this tumor suppressor gene in primary breast cancer . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The activity of cdk complexes is regulated in part by the association of a cyclin partner that acts as a positive effector and by two families of cdk inhibitors , the kinase inhibitor proteins ( KIP ) and the inhibitors of cdk 4 ( INK 4 ) , which act as negative effectors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Treatment with salicylate prevented PDGF induced downregulation of p 21 ( Waf 1 ) and p 27 ( Kip 1 ) but not of the Cdk 4 / 6 inhibitor p 16 ( Ink 4 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Time dependent change of G 1 cyclins , cdk 2 and cdk 4 after addition of AP showed that expression level of cdk inhibitors , INK 4 family , and p27KIP1 did not altered , while that of p21WAF1 was downregulated . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Second , to sequester p 16 ( INK4a ) and related INK 4 proteins , cyclin dependent kinase 4 ( CDK 4 ) was retrovirally transduced into normal human CD 34 ( + ) bone marrow cells and then cultured in myeloid colony forming cell ( CFC ) assays . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
RESULTS : The results of these experiments confirm that the levels of wild type tumor suppressor proteins , such as p 53 , pRB , PTEN , p 14 ( ARF ) , and p 16 ( INK 4 ) , are lost or severely reduced in most gliomas , and that epidermal growth factor receptor , 2human telomerase reverse transcriptase , and cyclin dependent kinase 4 are overexpressed frequently and with a few exceptions , almost exclusively , in glioblastomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
This mutation , R24C , renders the Cdk 4 protein insensitive to inhibition by INK 4 proteins including p 16 ( INK4a ) , a major candidate for the melanoma susceptibility locus . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Wide spectrum of tumors in knock in mice carrying a Cdk 4 protein insensitive to INK 4 inhibitors . ^^^ This mutation ( replacement of Arg 24 by Cys ) was first found in patients with hereditary melanoma and renders Cdk 4 insensitive to INK 4 inhibitors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Furthermore , induction of apoptosis by cdk 4 was abrogated by co transfection of p 16 ( INK 4 ) , or dominant negative cdk 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Novel insights into the INK 4 CDK4 / 6 Rb pathway : counter action of gankyrin against INK 4 proteins regulates the CDK 4 mediated phosphorylation of Rb . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We found that the mRNA expression of the cell cycle kinase ( CDK ) inhibitor inhibitor kinase ( INK ) p 18 ( INK 4 ) , a specific inhibitor of CDK 4 , 6 , which controls the activation of the retinoblastoma ( Rb ) tumor suppressor protein phosphorylation , was decreased in the brain of adult hCOX 2 homozygous transgenics . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Overexpression of D type cyclins or cdk 4 and inactivation of Ink 4 inhibitors are common in human tumors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We tested the hypothesis that cyclin dependent kinase inhibitors , specifically the inhibitors of the cyclin dependent kinase 4 ( INK 4 ) family , are targets for altered gene expression in GCTs . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In facilitating escape from G 1 growth restraints , Ras and CDK 4 alter the composition of cyclin D and cyclin E complexes and promote resistance to growth inhibition by INK 4 cyclin dependent kinase inhibitors . ^^^
Interacting proteins: Q8N726 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 . ^^^ Mutations in the CDK 4 gene conferring INK 4 resistance are associated with familial and sporadic melanoma in humans and result in a wide spectrum of tumors in mice . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Sequence analysis and in vitro kinase assays showed that most of the mutations that disrupted interactions with p 16 ( INK 4 ) also knocked out the activity of CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In the presence of INK 4 proteins , binding of Tax and Tax40N to CDK 4 counteracts against the inhibition of p 16 and p 18 and acts as the major path to regulate Tax mediated activation of CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Dominant activating mutations affecting codon 24 of the CDK 4 gene ( replacement of Arg 24 by Cys or His ) render CDK 4 insensitive to p 16 ( INK 4 ) inhibition and are responsible for melanoma susceptibility in some kindreds . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The potencies of binding and inhibition of IkappaBalpha are comparable to those of INK 4 proteins , the specific CDK 4 inhibitors that also contain ankyrin repeats . ^^^ Furthermore , we showed that INK 4 proteins and IkappaBalpha compete with each other for binding to CDK 4 . ^^^ To further understand the structural basis of IkappaBalpha CDK binding , we used different mutants of CDK 4 to show that there are notable differences between IkappaBalpha and INK 4 proteins in CDK 4 binding since the binding is affected differently by different CDK 4 mutations . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
A mutation in the gene encoding for Cdk 4 , Cdk4R24C , causes this kinase to be insensitive to INK 4 cell cycle inhibitors and induces beta cell hyperplasia in Cdk4R24C knockin mice . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : The p 16 ( INK 4 ) protein has been identified as a potent inhibitor of cyclin dependent kinase ( cdk ) 4 by blocking cdk 4 mediated phosphorylation of the tumor suppressor retinoblastoma ( Rb ) protein , thus allowing Rb mediated growth suppression . ^^^ METHODS : We examined immunohistochemical expression of p 16 ( INK 4 ) , cdk 4 , and Rb proteins in 38 BACs and correlated their expression levels with known clinicopathological features of the disease . ^^^ RESULTS : All BACs expressed cdk 4 , while 89 and 82 % expressed p 16 ( INK 4 ) and Rb proteins , respectively . ^^^ None of the clinicopathological factors correlated with p 16 ( INK 4 ) , cdk 4 , or Rb expression separately . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Using gene targeted mouse models , we report in this article that Cdk 4 resistance to INK 4 inhibitors , due to the Cdk 4 R24C mutation , strongly cooperates with p 27 ( Kip 1 ) deficiency in tumor development . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Cyclin D 1 was much more abundant in the infant than adult cells , but there was no difference according to the expression of cdk 4 , cdk 2 , cyclin E and cdk inhibitors ( p 16 ( Ink 4 ) ( p 16 ) , p 21 ( Cip1 / Waf1 ) ( p 21 ) and p 27 ( Kip 1 ) ( p 27 ) ) . 8 OHdG became high soon after cultivation , while it rapidly went down after day 2 both in the infant and adult cells . ^^^
Interacting proteins: Q8N726 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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
The expression of cyclins ( A , B 1 , D 1 , D 3 , E ) , cyclin dependent kinases ( CDK 2 ( 3 ) , CDK 4 ) , and the cyclin dependent kinase inhibitors ( CDKIs ) p 16 ( INK4A ) and p 21 ( CIP 1 ) was studied in 9 malignant human astrocytoma cell lines using northern blot analysis , immunocytochemistry , and immunoblotting to see if their altered expression contributed to astrocytoma proliferation . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Conversely , CDK 4 activity is inhibited when it is bound to the cyclin dependent kinase inhibitor , p 16 ( INK4A ) . ^^^ To investigate the molecular basis of the interactions between CDK 4 and cyclin D 1 or p 16 ( INK4A ) we performed site directed mutagenesis of CDK 4 . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Tumour derived mutations in INK4a and Cdk 4 map to interface contacts , solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a . . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p 16 ( INK4A ) protein and flavopiridol restore yeast cell growth inhibited by Cdk 4 . ^^^ Loss of Cdk 4 regulation can occur through overexpression of Cdk 4 catalytic subunit or its regulatory partner cyclin D 1 , or if the Cdk 4 specific inhibitory protein p 16 ( INK4A ) is inactive . ^^^ The fact that p 16 ( INK4A ) and flavopiridol negate Cdk 4 mediated suppression of yeast cell growth implies that this simple system can be used as a screen for identifying Cdk 4 specific antagonists which may mimic p 16 ( INK4A ) in the cancer cell cycle . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Lack of germ line mutations of CDK 4 , p 16 ( INK4A ) , and p 15 ( INK4B ) in families with glioma . ^^^ We hypothesized that germ line mutations in the p 16 ( INK4A ) , p 15 ( INK4B ) , or CDK 4 genes might contribute to some cases of familial gliomas . ^^^ We did not detect any functional mutations in the p 16 ( INK4A ) , p 15 ( INK4B ) , or CDK 4 genes , although two individuals did have a previously described A140T polymorphism in p 16 ( INK4A ) . ^^^ Thus , despite the association between the sporadic forms of high grade glioma and abnormalities of p 16 ( INK4A ) , p 15 ( INK4B ) , or CDK 4 , we found no evidence that germ line mutations in the coding region of these three genes predispose to inherited glial tumors . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Modeling mutations in the G 1 arrest pathway in human gliomas : overexpression of CDK 4 but not loss of INK4a ARF induces hyperploidy in cultured mouse astrocytes . ^^^ Nearly all human gliomas exhibit alterations in one of three genetic loci governing G 1 arrest : INK4a ARF , CDK 4 , or RB . ^^^ To discern the roles of CDK 4 amplification and INK4a ARF loss in gliomagenesis , we compared the behavior of astrocytes lacking a functional INK4a ARF locus with astrocytes overexpressing CDK 4 . ^^^ Either a deficiency of p 16 ( INK4a ) and p 19 ( ARF ) or an increase in Cdk 4 allows cultured astrocytes to grow without senescence . ^^^ Astrocytes overexpressing CDK 4 grow more slowly than INK4a ARF deficient astrocytes and convert to a tetraploid state at high efficiency ; in contrast , INK4a ARF deficient cells remain pseudodiploid , consistent with properties observed in human gliomas with corresponding lesions in these genes . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We have produced these combinations by simultaneously infecting tv a transgenic mice with vectors carrying cdk 4 and EGFR or by infecting tv a transgenic mice bearing a disrupted INK4a ARF locus with the EGFR carrying vector alone . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDK 4 gene amplification in osteosarcoma : reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons . ^^^ The INK4A gene , localized to human chromosome 9p21 , encodes p16INK4A , a tumor suppressor that functions at least in part through the inhibition of CDK 4 , a cyclin dependent kinase encoded by a gene at 12q13 . ^^^ To examine INK4A gene alterations in uncultured samples of osteosarcoma and the relationship between INK4A and CDK 4 alterations , we analyzed the INK4A and CDK 4 genes in 87 specimens from 79 patients . ^^^ INK4A deletion and CDK 4 gene amplification were determined by quantitative Southern blot analysis . ^^^ CDK 4 gene amplification was found in 6 of 67 samples , but not in tumors with INK4A alteration . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Induced expression of p 16 ( INK4a ) inhibits both CDK 4 and CDK 2 associated kinase activity by reassortment of cyclin CDK inhibitor complexes . ^^^ As expected , induction of p 16 ( INK4a ) results in a G 1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein ( pRb ) by the cyclin dependent kinases CDK 4 and CDK 6 . ^^^ Upon induction of p 16 ( INK4a ) , this complex is partly dissociated , and the majority of CDK 4 is found in lower molecular weight fractions consistent with the formation of a binary complex with p 16 ( INK4a ) . ^^^ Sequestration of CDK 4 by p 16 ( INK4a ) allows cyclin D 1 to associate increasingly with CDK 2 , without affecting its interactions with the CIP / KIP inhibitors . ^^^ Thus , upon the induction of p 16 ( INK4a ) , p 27 ( KIP 1 ) appears to switch its allegiance from CDK 4 to CDK 2 , and the accompanying reassortment of components leads to the inhibition of cyclin E CDK 2 by p 27 ( KIP 1 ) and p 21 ( CIP 1 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
To identify the possible genes included in the abnormal chromosome regions , selected cases were analyzed for P 53 , P 16 ( INK4a ) , RB , C MYC , N MYC , BCL 2 , BCL 6 , CDK 4 , and BMI 1 gene alterations . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutation testing in melanoma families : INK4A , CDK 4 and INK4D . ^^^ We report mutation screening of the INK4A and CDK 4 genes in 42 UK families . ^^^ A total of nine families were identified with INK4A mutations and none with CDK 4 exon 2 mutations . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDKN2A ( P 16 ( INK4a ) ) and CDK 4 mutation analysis in 131 Australian melanoma probands : effect of family history and multiple primary melanomas . ^^^ Mutation analysis of two genes involved in melanoma susceptibility ( CDKN2A / p16 ( INK4a ) and CDK 4 ) was undertaken in 131 probands with a family history of melanoma . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 and P11802	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p 53 , p 21 ( WAF / CIP1 ) , Rb , p 16 ( INK4A ) , CDK 4 and Cyclin D 1 , MIB 1 ( Ki 67 ) and BCL 2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx ( n = 26 ) , hypopharynx ( n = 10 ) and larynx ( n = 7 ) by applying immunohistochemistry to paraffin sections of tumor specimens . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p 16 ( INK4a ) tumor suppressor inhibits cyclin dependent kinases ( CDK 4 and CDK 6 ) . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
In addition to the INK4a locus , other genes involved in melanoma development are discussed here , in particular those genes that participate in the same functional pathway , such as CDK 4 and Rb , and p 53 , which is regulated by the alternative product of INK4a . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The prognoses of pancreatic cancer patients have been miserable even after radical surgery , and adjuvant therapy is necessary to improve the surgical results . p 16 ( INK4a ) ( p 16 ) is tight binding and inhibitory protein for cyclin dependent kinase 4 to induce G 1 arrest of the cell cycle . p 16 gene deletion is frequently identified in human pancreas cancer . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Moreover , ectopic expression of cyclin D 1 and Cdk 4 can stimulate the Brca 1 promoter in an E2F dependent manner , and this is inhibited by coexpression of the p 16 ( INK4a ) cyclin dependent kinase inhibitor . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
D cyclin cdk activity is required for Rb phosphorylation in 5 Jun transformed cells , since ectopic expression of the cdk 4 and cdk 6 specific inhibitor p 16 ( INK4A ) inhibits both DNA synthesis and cell proliferation . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Investigation of germline PTEN , p 53 , p 16 ( INK4A ) / p14 ( ARF ) , and CDK 4 alterations in familial glioma . ^^^ Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction ( PCR ) and direct sequencing of the PTEN , p 53 , p 16 ( INK4A ) / p14 ( ARF ) , and CDK 4 genes . ^^^ Thus , whereas germ line mutations of PTEN , p 53 , p 16 ( INK4A ) / p14 ( ARF ) , and CDK 4 are not common events in familial glioma , outside of familial cancer syndromes , point mutations of p 53 and hemizygous deletions and other rearrangements of the p 16 ( INK4A ) / p14 ( ARF ) tumor suppressor region may account for a subset of familial glioma cases . ^^^
Interacting proteins: Q8N726 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 . . ^^^ INK4A mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
To better understand these mechanisms in long term cultured lymphocytes we have characterized two human long term cultured IL 2 dependent T cell lines regarding telomere length , telomerase activity , and the expression of selected cell cycle regulators ( pRb , p 53 , cyclin E , cyclin D 1 , cyclin D 2 , cyclin D 3 , cdk 4 , p 16 ( INK4a ) , p 21 ( WAF 1 ) , p 27 ( KIP 1 ) , c myc , bcl 2 , and NPAT ) . ^^^ The growth inhibitory activity of p 16 ( INK4a ) seemed to be abrogated by enhanced expression of cyclin D 2 , cdk 4 , and c myc in one T cell line and overexpression of cyclin E in the second T cell line . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Although E2F 1 blocked IL 6 mediated terminal differentiation and its associated growth arrest , it did not prevent the rapid induction of both p 15 ( INK4B ) and p 16 ( INK4A ) , inhibition of cdk 4 kinase activity , and subsequent hypophosphorylation of pRb . ^^^
Interacting proteins: Q8N726 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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
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 . ^^^ These results suggest that p 16 ( INK4A ) may regulate cell cycle progression by inhibiting not only CDK 4 pRb kinase activity but also by modulating CDK 7 CTD kinase activity . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : The INK4a ARF locus encodes two tumor suppressor proteins , p 16 ( INK4a ) and p 14 ( ARF ) , that act through the Rb CDK 4 and p 53 pathways , respectively . ^^^ We examined the frequency of INK4a ARF , p 53 , and CDK 4 mutations in skin carcinomas from patients with xeroderma pigmentosum ( XP ) , a rare autosomal disease that is associated with a defect in DNA repair and that predisposes patients to skin cancer . ^^^ METHODS : DNA from skin cancers of 28 unrelated XP patients was screened for mutations in p 53 , INK4a ARF , and CDK 4 coding exons by single strand conformation polymorphism analysis and automated sequencing . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Expression of p 16 ( INK4a ) inhibited G ( 1 ) / S transition induced in MCF 7 cells by 17 beta estradiol ( E ( 2 ) ) with associated inhibition of both Cdk 4 and Cdk 2 associated kinase activities . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : : Inherited mutations in the CDKN2A tumor suppressor gene , which encodes the p 16 ( INK4a ) protein , and in the cyclin dependent kinase 4 ( CDK 4 ) gene confer susceptibility to cutaneous malignant melanoma . ^^^ The 113insArg mutant p 16 ( INK4a ) was unable to bind cdk 4 and cdk 6 in an in vitro binding assay . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Progression through the G 1 phase of the cell cycle requires phosphorylation of the retinoblastoma gene product ( pRb ) by the cyclin D dependent kinases CDK 4 and CDK 6 , whose activity can specifically be blocked by the CDK inhibitor p 16 ( INK4A ) . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
TRIP Br 1 is identical to the cyclin dependent kinase 4 ( cdk 4 ) binding protein p 34 ( SEI 1 ) , which renders the activity of cyclin D / cdk4 resistant to the inhibitory effect of p 16 ( INK4a ) during late G ( 1 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Genetic alteration of one or more components of the p 16 ( INK4A ) CDK 4 , 6 / cyclin D retinoblastoma pathway is found in more than half of all human cancers . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Semi quantitative RT PCR and Western blot analysis showed no change in the expression level of cyclin dependent kinase 4 ( CDK 4 ) , p 16 ( Ink4a ) or p 21 ( Cip 1 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
METHODS : We performed Western blot analysis of five cell cycle stimulating ( cyclins D 1 , E , B 1 , cdk 2 , cdk 4 ) and three cell cycle inhibiting ( p 16 ( INK4a ) , p 21 ( WAF 1 ) , Rb ) proteins in 41 endometrial carcinoma specimens . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : The cellular activities of four melanoma associated p 16 ( INK4a ) mutations ( Arg24Pro , Ala36Pro , Met53Ile , and Val126Asp ) were compared by use of inducible expression in stably transfected melanoma cells , deficient in expression of the endogenous protein , and compared with their ability to bind CDK 4 . ^^^ Functional impairment of melanoma associated p 16 ( INK4a ) mutants in melanoma cells despite retention of cyclin dependent kinase 4 binding . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In addition , senescence is associated with increased binding of the cyclin dependent kinase inhibitor ( CDK 1 ) p 16 ( INK4a ) to CDK 4 , down regulation of cyclin E protein levels ( and consequent loss of cyclin E / CDK2 activity ) , underphosphorylation of the retinoblastoma protein RB and subsequent increased levels of E2F4 RB repressive complexes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Senescence delay of human diploid fibroblast induced by anti sense p16INK4a expression . p 16 ( INK4a ) , a tumor suppressor gene that inhibits cyclin dependent kinase 4 and cyclin dependent kinase 6 , is also implicated in the mechanisms underlying replicative senescence , because its RNA and protein accumulate as cells approach their finite number of population doublings in tissue culture . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
RESULTS : Overexpressed p 16 ( INK4A ) protein was active as judged by its ability to bind to CDK 4 in a coimmunoprecipitation assay . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutations in CDK 4 and its key kinase inhibitor p 16 ( INK4a ) have been implicated in the genesis and progression of familial human melanoma . ^^^ The importance of the CDK 4 locus in human cancer first became evident following the identification of a germ line CDK 4 Arg24Cys ( R24C ) mutation , which abolishes the ability of CDK 4 to bind to p 16 ( INK4a ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Alterations of regulatory G ( 1 ) / S phase proteins like the retinoblastoma protein , cyclins D and E , cdk 4 and 6 , cdk inhibitors p 16 ( INK4A ) and p 15 ( INK4B ) , and p 53 are among the most frequent aberrations observed in human malignancies . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D 1 , Cdk 4 , INK4a and INK4b , pRb etc . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
One tumour with a single base deletion in the N terminus ( codon 8 ) of the CDKN2A / p16 ( INK4a ) gene carried a novel germ line mutation or a rare polymorphism ( Ile51Met ) in exon 2 of the CDK 4 gene . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Expression of Cdk 4 , Cdk 2 , p 16 ( INK4A ) , and p 27 ( KIP 1 ) did not change . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 and P11802	Pubmed	SVM Score :0.0
The three genes so far associated with familial melanoma susceptibility INK4A , CDK 4 and ARF , are all implicated in the molecular pathways controlling cell senescence . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Overexpression of the Cdk4 / 6 specific Cdk inhibitor of Cdk 4 p16 ( INK4A ) was associated with increased association of p 27 ( KIP 1 ) with Cdk 2 , concomitant with disruption of D cyclin / Cdk4 complexes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
While expression of the genes for cyclin D 1 , CDK 4 , and E2F1 increased in lung adenocarcinomas relative to normal lung , expression of p 15 ( Ink4b ) , p 16 ( Ink4a ) , p 21 ( Cip 1 ) , p 27 ( Kip 1 ) , p 57 ( Kip 2 ) , and pRb genes decreased in comparison . ^^^ Competitive RT PCR showed that the levels of cyclin D 1 and CDK 4 mRNAs were 2 and 3 fold higher , respectively , in lung adenocarcinomas than in normal lung , while the mRNAs for p 15 ( Ink4b ) , p 16 ( Ink4a ) , p 21 ( Cip 1 ) , p 27 ( Kip 1 ) , and pRb were 3 to 4 fold lower in adenocarcinomas than in normal lung , thus validating the macroarray findings . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In HepG 2 cells , this inhibition was associated with an arrest of the cell cycle in G ( 0 ) G ( 1 ) , increased cellular levels of p 21 ( CIP 1 ) , decreased levels of the hyperphosphorylated form of the retinoblastoma protein , and decreased levels of cyclin D 1 , but no significant changes were seen in the levels of the p 16 ( INK4a ) , p 27 ( KIP 1 ) , cyclin dependent kinase 4 , cyclin dependent kinase 6 , glycogen synthase kinase 3beta , or beta catenin proteins . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Cdk 4 activity was not required for cell cycle progression in these cells , and was constitutively inhibited through its association with p 16 ( INK4A ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The regulatory role of p 16 ( Ink4a ) , a potent Cdk 4 kinase inhibitor , on the kinase activity of Cdk 2 and Cdk 4 was also examined . ^^^ Raf induced p 16 ( Ink4a ) suppressor but this did not eliminate Cdk 4 kinase activity . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
TP 53 , CDKN2A ( p 16 ( INK4a ) ) , CDK 4 , MDM 2 , and EGFR . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The tumor suppressor protein p 16 ( INK4A ) ( p 16 ) forms a complex with Cdk 4 and inhibits kinase activity . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In an attempt to model oral cancer in a human cell based system , we analyzed normal oral epithelial keratinocytes with the pRB pathway dysregulated by loss of expression of the cyclin dependent kinase ( cdk ) 4 / cdk6 inhibitor p 16 ( INK4A ) and / or ectopic expression of cdk 4 or expression of the human papillomavirus ( HPV ) type 16 E 7 oncoprotein . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Overexpressing cyclin dependent kinase 4 ( Cdk 4 ) in human epidermal keratinocytes and human mammary epithelial cells not only prevents the p 16 ( INK4a ) associated premature growth arrest due to telomere independent stress ( e . g . , inadequate culture conditions ) , but also bypasses the ensuing telomere dependent senescence ( M 1 ) . ^^^ Overexpressed Cdk 4 in epithelial cells induces a dramatic upregulation of p 16 ( INK4a ) and milder upregulation of p 53 and p 21 ( WAF 1 ) , which become unresponsive to UV irradiation . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Moreover , the cells that overexpress p 16 ( ink4a ) or Cdk 4 ( N 158 ) show a delay in G ( 1 ) when made quiescent and restimulated to proliferate . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutational analysis of N ras , p 53 , CDKN2A ( p 16 ( INK4a ) ) , p 14 ( ARF ) , CDK 4 , and MC1R genes in human dysplastic melanocytic naevi . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We report here the use of multiple stabilizing substitutions to increase the stability of p 16 ( INK4a ) and furthermore , to restore Cdk 4 binding activity of several defective , cancer related mutant proteins . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Special reference is made to the fact that the known melanoma susceptibility genes in the human , Inhibitor A of [ cyclin dependent ] kinase 4 alternative reading frame ( INK4A ARF ) and cyclin dependent kinase 4 , are involved in the regulation of cellular senescence , and possible reasons why this should be so . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In our study , we screened HCCs resulting from HCV infection ( 51 cases ) , HBV infection ( 26 cases ) or excess alcohol intake ( 23 cases ) for alterations in genes involved in the RB 1 pathway ( p 16 ( INK4a ) , p 15 ( INK4b ) , RB 1 , CDK 4 and cyclin D 1 ) , the p 53 pathway ( p 53 , p 14 ( ARF ) and MDM 2 ) and the Wnt pathway ( beta catenin , APC ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The expression patterns of the proteins p 53 , pRb , cyclinD 1 , cdk 4 , p 21 ( CIP1 / WAF1 ) , p 16 ( INK4a ) , bcl 2 , and mib 1 / ki 67 were analyzed in pretreatment tumor biopsies of 53 patients with advanced nonresectable head and neck squamous cell carcinomas ( mainly UICC 4 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Three lines of evidence established that p 16 ( INK4a ) is an essential effector of hSNF 5 induced cell cycle arrest . 1 ) Overexpression of p 16 ( INK4a ) mimics the effect of hSNF 5 induction and leads to cellular senescence . 2 ) Expression of a p 16 ( INK4a ) insensitive form of CDK 4 obstructs hSNF 5 induced cell cycle arrest . 3 ) Inhibition of p 16 ( INK4a ) activation by siRNA blocks hSNF 5 mediated cellular senescence . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In contrast , inheritance of the p 16 ( Ink4a ) insensitive Cdk 4 ( R24C ) mutation leads to spontaneous transformation of MEF cultures in vitro and , in vivo , hyperproliferative disorders that progress to cancer . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Currently , we assessed the expression of cell cycle regulatory proteins ( pRb , cyclin D 1 , p 16 ( INK4A ) and cdk 4 ) in 48 sporadic endometrial cancers , and investigated these tumors for a possible relationship between aberrant protein staining and clinicopathological variables of cancer and RB LOH . ^^^ There was abnormal pRb , cyclin D 1 , p 16 ( INK4A ) and cdk 4 immunoreactivity in 2 % , 50 % , 6 % and 25 % of cases , respectively . ^^^ However , there was significant correlation neither between the cell cycle regulators nor between the frequency of pRb , p 16 ( INK4A ) and cyclin D 1 abnormalities and clinicopathological variables of cancer , but a significant correlation did exist between cdk 4 staining and the clinical stage of disease ( P < 0 . 05 , Fisher ' s exact test ) . ^^^
Interacting proteins: Q8N726 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: Q8N726 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 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Based on the concept that tumor suppressor genes are involved in the pathogenesis of urinary bladder carcinogenesis , we analysed the mRNA expression of the retinoblastoma ( Rb ) and p 16 ( CDKN 2 , INK4A , MTS 1 ) genes as well as of the proto oncogene cyclin D dependent kinase 4 ( CDK 4 ) in 71 transitional cell carcinomas ( TCC ) of the urinary bladder in relation to the tumor grades and stages , and with reference to certain lifestyle and occupational risk factors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Furthermore , Ha Ras ( G12V ) upregulated p 16 ( INK4a ) and downregulated cyclin dependent kinase Cdk 4 in human esophageal keratinocytes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Structural comparison with p 16 ( INK4A ) identified several residues of gankyrin that are potentially important for CDK 4 binding , whereas observation of the thiol proton of C 180 indicated a well structured Rb binding site in the helical region of the sixth ankyrin repeat . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The following genes exhibited moderate changes in methylation : O 6 methylguanine DNA methyltransferase ( MGMT ) ( 20 % , 13 / 65 ) , mutL homolog 1 , colon cancer , nonpolyposis type 2 ( E . coli ) ( hMLH 1 ) ( 18 % , 12 / 65 ) , cyclin dependent kinase inhibitor 2A ( melanoma , p 16 , inhibits CDK 4 ) ( p 16 ( INK4a ) ) ( 10 % , 10 / 65 ) , methylated in tumor 1 ( MINT 1 ) ( 15 % , 10 / 65 ) , methylated in tumor 31 ( MINT 31 ) ( 11 % , 7 / 65 ) . ^^^
Interacting proteins: Q8N726 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: Q8N726 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 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
RB pathway mutations , especially at the CDK 4 and INK4A loci , are hallmarks of melanomagenesis . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Melanomas also commonly show impairment of the p 16 ( INK4A ) CDK 4 Rb and ARF HDM 2 p53 tumor suppressor pathways . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : We determined the mRNA expression of p 1 ( INK4A ) , p 14 ( ARF ) , CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 by quantitative reverse transcription PCR in 38 cases of GISTs and correlated the findings with clinicopathologic factors , including mutation analysis of KIT and PDGFRA . ^^^ GISTs with low mRNA expression of the CDKN2A transcripts p 16 ( INK4A ) and p 14 ( ARF ) but high mRNA expression of CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 were associated with aggressive clinical behavior and unfavorable prognosis , whereas GISTs with a low mRNA expression of CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 were not . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The tumour suppressor ARF ( alternative reading frame ) is encoded by the INK4a ( inhibitor of cyclin dependent kinase 4 ) / ARF locus , which is frequently altered in human tumours . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Dissection of CDK 4 binding and transactivation activities of p 34 ( SEI 1 ) and comparison between functions of p 34 ( SEI 1 ) and p 16 ( INK4A ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Upregulation of p 16 ( INK4A ) , Hsp 90 , and Cdc 37 genes ; an increase in Cdc 37 Cdk4 complexes ; and a decrease in p 16 ( INK4A ) Cdk 4 complexes occurred in preneoplastic liver , nodules , and hepatocellular carcinoma of F 344 rats . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Human melanoma susceptibility is often characterized by germ line inactivating CDKN2A ( INK4A / ARF ) mutations , or mutations that activate CDK 4 by preventing its binding to and inhibition by INK4A . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
METHODS : Genes for the CDKIs p 16 ( INK4a ) and p 18 ( INK4c ) , a constitutively active form of retinoblastoma ( RB ) gene product , cyclin D 1 , and CDK 4 , were transferred into RA synovial fibroblasts ( RASFs ) . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Lesions in the p 16 cyclin D CDK 4 Rb and ARF Mdm 2 p 53 pathways occur so frequently in cancer , regardless of patient age or tumor type , that they appear to be part of the life history of most , if not all , cancer cells . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In this report we present the results of mutational analysis of the CDKN2B , CDKN2C , CDK 4 , p 53 genes and 5 ' UTR of the CDKN2A gene in a set of 44 sporadic primary melanomas , which had been earlier analysed for mutations in the CDKN2A ( p16 / p14 ( ARF ) ) gene . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
These included 3 genes coding for proteins in the p 53 pathway ( i . e . , TP 53 , p 14 ( ARF ) , and MDM 2 ) , 4 in the Rb 1 pathway ( i . e . , CDKN2A , CDKN2B , RB 1 , and CDK 4 ) , as well as PTEN and epidermal growth factor receptor . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Evaluation of germline CDKN2A , ARF , CDK 4 , PTEN , and BRAF alterations in atypical mole syndrome . ^^^ Germline mutations in the CDKN2A , ARF , CDK 4 and somatic mutations in the PTEN and BRAF genes have been associated with melanoma . ^^^ No sequence alterations in the coding regions or in the splice junctions of CDKN2A , ARF , CDK 4 , PTEN or BRAF were identified . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
These included three genes coding for proteins in the p 53 pathway ( TP 53 , p 14 ( ARF ) and MDM 2 ) , four in the Rb 1 pathway ( CDKN2A , CDKN2B , RB 1 and CDK 4 ) and PTEN and EGFR . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
There were no mutations in ARF or CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Studies have shown that homozygous deletion of the cyclin dependent kinase 4 inhibitor ( CDK4I ) gene , which is mapped to chromosome 9p21 , is frequently observed in various types of human cancers . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Recently , it has been shown that the homozygous deletion of the cyclin dependent kinase 4 inhibitor ( CDK4I ; p 16 ) gene , which is mapped to chromosome 9p21 , is frequently observed in a wide spectrum of human cancers , including leukemias . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Rarity of somatic and germline mutations of the cyclin dependent kinase 4 inhibitor gene , CDK4I , in melanoma . ^^^ Recently , the inhibitor of cyclin dependent kinase 4 ( CDK4I ; also known as p16INK4 , multiple tumor suppressor 1 , or CDKN 2 gene ) has been mapped to 9p21 and shown to be mutated or deleted in a large fraction of cell lines derived from many tumor types , including melanoma , suggesting that this gene could be a melanoma suppressor gene . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p 16 gene ( MTS 1 or CDK4I ) encoding an inhibitor of cyclin dependent kinase 4 ( cdk 4 ) , has been reported to be deleted in various tumor cell lines , including lines derived from leukemic cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We report homozygous deletion of the recently identified multiple tumor suppressor 1 ( MTSI ) / cyclin dependent kinase 4 inhibitor ( CDKN 2 ) gene mapped to 9p21 , which encodes the p 16 protein , a regulator of cyclin dependent kinase 4 , in six of 16 HNSCC cell lines . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDKN 2 and CDKN2B belong to a family of cyclin dependent kinase 4 inhibitors ( INK 41 ) and control cell proliferation during the G 1 phase of the cell cycle . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : The CDKN 2 gene encodes the human cyclin dependent kinase 4 inhibitor . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Homozygous deletion frequency and expression levels of the CDKN 2 gene in human sarcomas relationship to amplification and mRNA levels of CDK 4 and CCND 1 . ^^^ Homozygous deletions of the putative tumour suppressor gene CDKN 2 , which encodes an inhibitor of cdk 4 , have been detected in a high percentage of cancer cell lines of various histological types . ^^^ Amplifications of CDK 4 and CCND 1 ( cyclin D 1 ) were observed in 11 % and 4 % of the sarcomas respectively , but never in tumours with CDKN 2 deletions . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
These alterations include deletions of negative regulatory elements ( TP 53 , CDKN 2 , MTS 2 ) and amplification of positive factors ( MDM 2 , CDK 4 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The CDKN 2 gene located on chromosome 9p21 encodes the cyclin dependent kinase 4 inhibitor p 16 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDKN 2 encodes a M ( r ) 16 , 000 protein ( p 16 ) that plays a key role in cell cycle control by binding to the cyclin dependent kinase 4 enzyme and inhibiting its ability to phosphorylate critical substrates necessary for transition past the G 1 phase of the cell cycle . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The cyclin dependent kinase 4 inhibitor ( CDKN 2 ) gene , which maps to 9p21 , has been implicated by the finding of a high frequency of biallelic deletions in leukemic cell lines . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The CDKN 2 gene that encodes the cell cycle regulatory protein cyclin dependent kinase 4 inhibitor ( p 16 ) has recently been mapped to chromosome 9p21 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDKN 2 ( p16 / MTS1 ) gene deletion or CDK 4 amplification occurs in the majority of glioblastomas . ^^^ Amplification of the CDK 4 gene was present in 7 of 14 ( 50 % ) glioblastomas and 3 of 11 ( 27 % ) anaplastic astrocytomas with no losses at the CDKN 2 locus as well as in 2 of 32 ( 6 % ) glioblastomas with CDKN 2 losses . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Homozygous deletions of the cyclin dependent kinase 4 ( CDK 4 ) inhibitor gene CDKN 2 ( p 16 , MTS 1 ) have been demonstrated to occur frequently in human cancer cell lines of different origin . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Involvement of the cyclin dependent kinase 4 inhibitor ( CDKN 2 ) gene in the pathogenesis of lymphoid blast crisis of chronic myelogenous leukaemia . ^^^ Recent data suggest that homozygous deletion of the cyclin dependent kinase 4 inhibitor gene ( CDKN 2 ) , a putative tumour suppressor gene located on chromosome 9p21 , represents a common genetic event in human cancer . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Although a low frequency of CDKN 2 DNA aberrations was observed , the high number of tumours that lacked CDKN 2 expression but showed overexpression of CDK 4 and / or CCND 1 , suggest that functional inactivation of pRb through this pathway may be involved in the development or progression of sporadic human melanomas . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The cyclin dependent kinase 4 inhibitor gene CDKN 2 , localized at chromosome region 9p21 , has been shown to be a familial melanoma gene , though we found that mutations of it are rare in uncultured sporadic melanomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The CDKN 2 gene , encoding the cyclin dependent kinase 4 inhibitor p 16 , is a putative tumour suppressor gene because it is frequently altered in many malignant tumours . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
These data strongly support the idea that deregulation of the CDK4 / cyclin D pathway , via CDKN 2 or CDK 4 mutations , is of biological significance in the development of melanoma . ^^^ To shed light on the role of these alterations in the development and progression of sporadic melanoma , 12 primary melanomas and 9 corresponding metastases were analyzed for CDKN 2 and CDK 4 gene mutations . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p 16 gene ( MTS 1 , CDKN 2 , p16INK4A , CDKI ) encoding an inhibitor of cyclin dependent kinase 4 ( cdk 4 ) has been found to be deleted in various types of tumors , including leukemia , and is thought to code for a tumor suppressor gene . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Germline mutations in CDKN 2 on chromosome 9p21 , which codes for the cyclin D kinase inhibitor p 16 , and more rarely , mutations in the gene coding for CDK 4 , the protein to which p 16 binds , underlie susceptibility in some melanoma families . ^^^ We have sequenced all exons of CDKN 2 and analysed the CDK 4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The activities of CDK 4 is constrained by inhibitors such as p 16 , the product of the CDKN 2 in tumor cells and primary tumors suggests that p 16 acts as a tumor suppressor . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
These alterations lead to changes in the expression of several genes ; protein 53 ( p 53 ) , retinoblastoma ( RB ) , interferon ( INF ) alpha / beta , cyclic AMP dependent kinase number 2 ( CDKN 2 ) , mutated in multiple advanced cancers 1 ( MMAC 1 ) , deleted in colon carcinoma ( DCC ) , epidermal growth factor receptor ( EGFR ) , platelet derived growth factor ( PDGF ) , platelet derived growth factor receptor ( PDGFR ) , MDM 2 , GL 1 , CDK 4 and SAS during the genesis and progression of human gliomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The gene CDKN 2 , which encodes the protein p 16 , a cyclin dependent kinase 4 inhibitor , maps to 9p21 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In melanoma prone kindreds with CDKN 2 wild type status , a mutation in one of the targets of p 16 , cyclin dependent kinase 4 ( CDK 4 ) was reported , which abolishes p 16 inhibition . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p 16 protein is encoded by the CDKN 2 gene , and functions as an inhibitor of cyclin dependent kinase 4 and 6 ( CDK4 / 6 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Absence of mutations in the CDKN 2 binding site of CDK 4 in childhood acute lymphoblastic leukemia . ^^^ Here we report the absence of point mutations in the CDKN 2 binding site of CDK 4 in 100 cases of childhood ALL , 2 cases of childhood chronic myeloid leukemia and 9 hematologic cell lines screened by PCR SSCP ( polymerase chain reaction single stranded conformational polymorphism gel electrophoresis ) , thereby minimizing the possibility of the existence of these specific CDK 4 mutations in childhood ALL . . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Human glioblastomas with no alterations of the CDKN2A ( p16INK4A , MTS 1 ) and CDK 4 genes have frequent mutations of the retinoblastoma gene . ^^^ A series of 195 human gliomas were studied as to the status of their CDKN2A , CDK 4 and RB 1 genes . ^^^ Among 120 glioblastomas , 40 % had no wild type CDKN2A gene , 12 % amplified the CDK 4 gene , and 14 % had no wild type RBI gene . ^^^ 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 . ^^^ Thus some aberration of the CDKN2A , CDK 4 and RB 1 genes appears to be almost obligatory in glioblastomas . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDKN2A ( 9p21 ) and CDK 4 ( 12q13 ) have been identified as melanoma susceptibility genes in certain familial melanoma ( FM ) kindreds . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
To evaluate whether gcGBM may also represent a genetically defined subgroup of GBM , we analyzed a series of 19 gcGBMs for mutations in the TP 53 gene for amplification of the EGFR and CDK 4 genes and for homozygous deletions in the CDKN2A ( p16 / MTS1 ) gene . ^^^ Seventeen of nineteen gcGBMs carried TP 53 mutations whereas EGFR and CDK 4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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 . ^^^ In the 11 cell lines that expressed functional p 16 , microsatellite analysis revealed loss of heterozygosity at the markers immediately surrounding CDKN2A in five cases , and the previously characterized R24C mutation of CDK 4 was identified in one of the remaining 6 lines . ^^^ These data indicate that 55 of 60 ( 92 % ) melanoma cell lines demonstrated some aberration of CDKN2A or CDK 4 , thus suggesting that this pathway is a primary genetic target in melanoma development . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Functional studies revealed that the CDKN2A variant carrying the M 531 change was unable to bind effectively to CDK 4 , showing that this mutation is of pathological significance . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Analysis of the CDKN2A , CDKN2B and CDK 4 genes in 48 Australian melanoma kindreds . ^^^ Germline mutations within the cyclin dependent kinase inhibitor 2A ( CDKN2A ) gene and one of its targets , the cyclin dependent kinase 4 ( CDK 4 ) gene , have been identified in a proportion of melanoma kindreds . ^^^ We have previously reported the identification of germline CDKN2A mutations in 7 / 18 Australian melanoma kindreds and the absence of the R24C CDK 4 mutation in 21 families lacking evidence of a CDKN2A mutation . ^^^ All of these families have now been screened for mutations within CDKN2A and CDK 4 , as well as for mutations within the CDKN2A homolog and 9p21 neighbor , the CDKN2B gene , and the alternative exon 1 ( E1beta ) of CDKN2A . ^^^ In none of the ' CDKN2A negative ' families was melanoma found to segregate with either an untranscribed CDKN2A allele , an R24C CDK 4 mutation , a CDKN2B mutation , or an E1beta mutation . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The gene for the cyclin dependent kinase 4 inhibitor , CDKN2A , is preferentially deleted in malignant mesothelioma . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Twenty primary central nervous system lymphomas ( PCNSL ) from immunocompetent patients ( nineteen B cell lymphomas and one T cell lymphoma ) were investigated for genetic alterations and / or expression of the genes BCL 2 , CCND 1 , CDK 4 , CDKN1A , CDKN2A , MDM 2 , MYC , RB 1 , REL , and TP 53 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Surprisingly , at the DNA level alone , 96 % ( 43 / 45 ) of melanoma cell lines examined were found to be deleted / mutated / methylated for CDKN2A ( 34 / 45 ) , homozygously deleted for CDKN2A ' s neighbor and homolog CDKN2B ( 6 / 45 ) , and / or mutated / amplified for CDK 4 ( 5 / 45 ) . ^^^ In two of these 43 cases , homozygous deletions of CDKN2A were detected along with a CDK 4 mutation or amplification of the cyclin D 1 ( CCND 1 ) gene . ^^^ These results suggest that ( 1 ) only melanoma cells with alterations in this pathway can be propagated in culture , and ( 2 ) the homozygous deletions on 9p21 in the cell lines , which are also mutated / amplified for CDK 4 or CCND 1 , could serve to target tumor suppressor genes other than CDKN2A . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The vast majority of glioblastomas have CDKN2A , CDK 4 , or RB gene alterations that perturb the p 16 cdk4 pRb cell cycle regulatory cascade . ^^^ Homozygous deletion of the CDKN2A gene was detected in 12 of 25 ( 48 % ) cases , CDK 4 amplification in 4 of 25 ( 16 % ) tumors , and loss of heterozygosity at the RB gene in 8 of 22 ( 36 % ) informative cases . ^^^ From a practical point of view , although p 16 immunonegativity does not necessarily indicate CDKN2A deletion , diffuse positive p 16 immunostaining strongly suggests either CDK 4 amplification or RB loss and excludes CDKN2A deletion . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Osteosarcomas often suffer mutations of the RB ( retinoblastoma ) gene , with resultant inactivation of the pRb protein . pRb is one component in a cell cycle control pathway that includes the p 16 ( encoded by the CDKN2A gene ) and cyclin dependent kinase 4 ( cdk 4 , encoded by the CDK 4 gene ) proteins . ^^^ We therefore sought to determine whether the CDKN2A and CDK 4 genes were altered in those osteosarcomas that lacked RB inactivation . ^^^ Twenty one osteosarcomas ( 2 low grade and 19 high grade ) were evaluated for homozygous deletion of the CDKN2A gene , CDK 4 amplification , and allelic loss of the RB gene , as well as for expression of p 16 and pRb proteins . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The CDKN2A gene located on chromosome region 9p21 encodes the cyclin dependent kinase 4 inhibitor p16 / INK4A , a negative cell cycle regulator . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The same mutation at this site in other tumors has been shown to alter the CDKN2A protein ' s ability to bind CDK 4 kinase , which may lead to uncontrolled cell cycling . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Amplification of the cyclin dependent kinase 4 ( CDK 4 ) gene , located at 12q13 q 14 , has been found as an alternative genetic alteration to CDKN2A inactivation in various human tumors including malignant gliomas and sarcomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutations of TP 53 , amplification of EGFR , MDM 2 and CDK 4 , and deletions of CDKN2A in malignant astrocytomas . ^^^ The genetic alterations analyzed were : deletion of CDKN2a / p16 gene , TP 53 mutations , and amplification of EGFR , MDM 2 and CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Normal repair of ultraviolet radiation induced DNA damage in familial melanoma without CDKN2A or CDK 4 gene mutation . ^^^ While a proportion of familial melanoma kindreds exhibit germline mutations in the cell cycle regulatory gene CDKN2A ( p16INK4a ) or its protein target , cyclin dependent kinase 4 ( CDK 4 ) , the biochemical basis of most familial melanoma is unknown . ^^^ We have examined lymphoblastoid cell lines from melanoma affected and unaffected individuals from large hereditary melanoma kindreds which are not attributable to CDKN2A or CDK 4 gene mutation . ^^^ These results indicate that melanoma susceptibility genes other than CDKN2A and CDK 4 do not impair net capacity to repair UV induced DNA damage . . ^^^
Interacting proteins: Q8N726 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 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In total , 11 / 12 MPNSTs showed DNA changes in one or more of the genes CDKN2A , CDKN2B , RB 1 , CDK 4 , MDM 2 , and CCND 2 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The 7 families without apparent CDKN2A involvement were also negative for hot spot exon 2 mutation of CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
More focussed molecular genetic analyses revealed neither aberrations of the TP 53 and CDKN2A tumor suppressor genes nor amplification of the EGFR , CDK 4 , and MDM 2 proto oncogenes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The scarcity of such cases generally requires that molecular analyses of PMAs are based on the utilization of paraffin embedded material , and here we have used 39 such specimens to examine the incidence and prognostic significance of oncogene and tumor suppressor gene alterations ( including amplifications of EGFR , CDK 4 , and MDM 2 as well as inactivating mutations of CDKN2A , TP 53 , and PTEN ) in these tumors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We have previously reported that approximately two thirds of glioblastomas ( GBs ) had abnormalities of G 1 S transition control either by mutation / homozygous deletion of RB 1 or CDKN2A p16INK4A ) , or amplification of CDK 4 ( K . ^^^ Sixty seven percent of GBs ( 91 / 136 ) and 21 % of AAs ( 8 / 39 ) had abnormalities of the G 1 S control system either by mutation / homozygous deletion of RB 1 , CDKN2A or CDKN2B , or amplification of CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In addition , single strand conformation analysis failed to reveal point mutations in the Cdk 4 amino terminal domain that is important for its association with Cdkn2a gene products . ^^^
Interacting proteins: Q8N726 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 . ^^^ 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Specific alterations of the EGFR , CDK 4 , CDKN2A , TP 53 , DMBT 1 , NF 2 , and PTEN genes were analyzed in addition . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
S . melanoma prone families with CDKN2A and CDK 4 mutations . ^^^ METHODS : We compared 104 CMM patients from 17 CDKN2A families and 12 CMM case subjects from two CDK 4 families . ^^^ RESULTS : The median age at CMM diagnosis ( P = . 70 ) and the median numbers of CMMs ( P = . 73 ) did not differ between CMM case subjects from CDKN2A versus CDK 4 families . ^^^ Analyses of recurrent CDKN2A and CDK 4 mutations suggested common haplotypes . ^^^ Despite hypothetical differences in the mechanisms of action between CDKN2A and CDK 4 , clinical factors were indistinguishable between CMM case subjects from CDKN2A versus CDK 4 families . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The CDKN2A gene has been implicated in cutaneous malignant melanoma ( CMM ) in about 40 % of families with linkage to chromosome 9p21 , while a small proportion of families have mutations in the CDK 4 gene . ^^^ We have not found mutations either in exon 1 beta of the CDKN2A gene or in exon 2A of CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutation analysis was performed on a panel of 39 sporadic metastatic melanomas , 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK 4 germline mutations . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Low prevalence of germline CDKN2A and CDK 4 mutations in patients with early onset melanoma . ^^^ Both subsets of patients with melanoma are at risk for harboring germline CDKN2A or CDK 4 mutations . ^^^ OBJECTIVE : We set out to prospectively determine the prevalence of CDKN2A and CDK 4 mutations in a group of young patients with melanoma . ^^^ MAIN OUTCOME MEASURE : We used a combination of single strand conformation analysis and direct sequencing of samples of peripheral blood leukocyte DNA to search for mutations in exons 1alpha , 1beta , 2 , and 3 of CDKN2A and in exon 2 of CDK 4 . ^^^ CONCLUSIONS : Germline CDKN2A and CDK 4 mutations are not common in patients who develop melanoma at an early age . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In addition , only three families worldwide have been reported with germline mutations in a gene other than CDKN2A ( i . e . , CDK 4 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Analysis of the CDKN2A and CDK 4 genes and HLA DR and HLA DQ alleles in two Spanish familial melanoma kindreds . ^^^ This study evaluated the human leucocyte antigen ( HLA ) class 2 genotype and the presence of mutations in CDKN2A and CDK 4 genes in 2 families with very different clinical features . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In rare families , susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK 4 , with more common , less penetrant genes also postulated . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDKN2A and CDK 4 mutation analysis in Italian melanoma prone families : functional characterization of a novel CDKN2A germ line mutation . ^^^ Physical interaction between CDKN2A / p16 and CDK 4 proteins regulates the cell cycle progression through the G 1 phase and dysfunction of these proteins by gene mutation is implicated in genetic predisposition to melanoma . ^^^ We analysed 15 Italian melanoma families for germ line mutations in the coding region of the CDKN2A gene and exon 2 of the CDK 4 gene . ^^^ Our results , obtained in a heterogeneous group of families , support the view that inactivating mutations of CDKN2A contribute to melanoma susceptibility more than activating mutations of CDK 4 and that other genetic factors must be responsible for melanoma clustering in a high proportion of families . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We selected 100 patients who displayed multiple primary melanoma ( MPM ) without any known melanoma cases recorded within their families and looked for germline mutations in the two melanoma predisposing genes identified to date , CDKN2A and CDK 4 exon 2 . ^^^ Nine patients ( 9 % ) had germline mutations in CDKN2A , whereas none carried germline mutations in exon 2 of CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Correlation of histology and molecular genetic analysis of 1p , 19q , 10q , TP 53 , EGFR , CDK 4 , and CDKN2A in 91 astrocytic and oligodendroglial tumors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Molecular genetic analysis of one tumor revealed no TP 53 mutation ( exons 4 10 ) , no loss of CDKN2A , and no amplification of EGFR , CDK 4 or MDM 2 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In the current study , the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A , CDK 4 , or not yet identified genes . ^^^ Blood was obtained for genetic studies ; genotyping for CDKN2A and CDK 4 was performed . ^^^ RESULTS : All the families were found to have members with dysplastic nevi and melanoma ; 17 had mutations in CDKN2A , 2 had mutations in CDK 4 , and 14 had no mutations in either gene identified . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Molecular genetic analysis of the TP 53 , PTEN , CDKN2A , EGFR , CDK 4 and MDM 2 tumour associated genes in supratentorial primitive neuroectodermal tumours and glioblastomas of childhood . ^^^ To identify molecular genetic markers that may distinguish sPNET and GBM , we investigated 12 cerebral sPNETs and six GBMs from paediatric patients for genetic alterations of the TP 53 , PTEN , CDKN2A , EGFR , CDK 4 and MDM 2 genes , as well as for allelic loss on chromosome arms 10q and 17p . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Amplification of CDK 4 or MDM 2 or homozygous deletion of CDKN2A was not detected . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
A proportion of melanoma prone individuals in both familial and non familial contexts has been shown to carry inactivating mutations in either CDKN2A or , rarely , CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In the past several years , two major susceptibility genes for melanoma , CDKN2A and CDK 4 , have been identified , but the two genes together account for a minority of familial melanoma . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Two high penetrance susceptibility genes , CDKN2A and CDK 4 , have so far been identified and mapping is ongoing to localize and identify others . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In terms of genetic factors , the discovery of two genes CDKN2A and CDK 4 has been a great advance with more understanding of melanocyte biology in relation to defects in senescence . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Although mutations in two genes , CDKN2A and CDK 4 , have been shown to confer an increased risk of CMM , they account for only 20 % 25 % of families with multiple cases of CMM . ^^^ Therefore , to localize additional loci involved in melanoma susceptibility , we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases , in which CDKN2A and CDK 4 involvement has been excluded . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Putative tumour suppressor genes CDKN2A and CDKN2B ( on chromosome 9p21 ) and CDKN2A interacting cell growth regulatory genes CDK 4 and Id 1 have been demonstrated to be involved in the pathogenesis of malignant melanoma ( MM ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In human familial melanoma , 3 risk susceptibility genes are already known , CDKN2A , CDK 4 and MC1R . ^^^ As we had previously excluded the MeLiM CDKN2A gene , we paid special attention to CDK 4 and MC1R , as well as to other candidates such as BRAF and the SLA complex , mapping them on the swine radiation hybrid map and / or isolating close microsatellite markers to introduce them into the genome scan . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
To evaluate the mutational profiles associated with BRAF mutations in human melanoma , we have studied BRAF , RAS , PTEN , TP 53 , CDKN2A and CDK 4 genes and their expression in melanoma lesions . ^^^ The results revealed novel missense mutations in the BRAF , PTEN , CDKN2A and CDK 4 genes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
DNA sequence copy number losses were identified for PDGFB ( 44 % ) ; D17S125 ( 39 % ) ; AKT 3 ( 28 % ) ; and RASSFI , FHIT , CDKN2A ( p 16 ) , and SAS ( CDK 4 ) ( 28 % each ) . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDK 4 expression did not correlate with CDKN2A methylation status . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Of these , 238 cases ( 34 familial , 14 non familial multiple primary and 190 non familial single primary melanomas ) were consecutively enrolled for screening of the CDKN2A and CDK 4 genes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Germline mutations in two genes that play a pivotal role in controlling cell cycle and division CDKN2A and cyclin dependent kinase 4 ( CDK 4 ) have been detected in autosomal , dominant , high penetrance familial melanoma cases . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
PURPOSE : We have studied a consecutive case series of patients with multiple primary melanoma ( MPM ) for the involvement of the melanoma susceptibility loci CDKN2A and CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Rarely , melanoma susceptibility is increased more than tenfold by heritable mutations in the cell cycle regulatory genes CDKN2A and CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Germline CDKN2A and CDK 4 status on the familial melanoma cases and clinical features associated with mutational status were then used to build a multiple logistic regression model to predict carrier probability and performance of model on external validation . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We performed a genome wide scan of two Danish pedigrees with multiple cases of OMM ( N = 10 ) and CMM ( N = 3 ) and other malignancies ( with no germline mutations in CDKN2A , CDK 4 , BRCA 1 , and BRCA 2 ) to identify melanoma susceptibility genes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
CDKN2A and CDK 4 genes residing on chromosomes 9p21 and 12q14 , as well as MC1R gene located at 16q24 are main candidates responsible for melanoma development and progression . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Major risk factors for melanoma include many nevi , especially dysplastic nevi , fair pigmentation , freckling , poor tanning ability , and germ line mutations in the CDKN2A , CDK 4 , or MC1R genes . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Age does not appear to be a major indicator of CDKN2A or CDK 4 mutations in melanoma patients in Spain . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We thus set out to assess how recurrent patterns of genetic injury at three critical human melanoma loci CDKN2A , TP 53 , and CDK 4 cooperate to disrupt both RB and p 53 pathways . ^^^ Although homozygous deletion of all three critical CDKN2A exons ( exons 1 beta , 1 alpha , and 2 ) represent the most common mechanism , concurrent loss of CDKN2A ( Exon 1 alpha ) and CDKN2A ( Exon 1 beta ) and simultaneous point mutagenesis of CDK 4 and TP 53 reflect alternative cassettes of dual inactivation . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We primarily used a unique Utah genealogical resource to identify independent melanoma prone families whom we tested for mutations in CDKN2A , cyclin dependent kinase 4 , and alternate reading frame . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : Melanoma risk factors include fair pigmentation , multiple nevi , low DNA repair capacity , and CDKN2A or CDK 4 mutations . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In familial melanoma , germline mutations in two genes , CDKN2A and CDK 4 , that play a pivotal role in controlling cell cycle and division . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
METHODS : A search for loss of heterozygosity ( LOH ) on chromosome 1p , 9p , 10q , 19q , EGFR ( epidermal growth factor receptor ) , CDK 4 , and MDM 2 ( mouse double minute ) amplifications , CDKN2A ( INK4A / ARF ) homozygous deletions , p 53 expression , was performed in a series of 220 primary glioblastomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The last discovery concern a known gene , MTS 1 ( Multiple Tumor suppressor ) , encoding a protein of M ( r ) 16K , intrinsic component of the cell cycle machinery . p 16 protein inhibits an enzyme called CDK 4 ( cyclin dependent kinase 4 ) which is a kinase implicated in the control of cell proliferation between the G 1 and S phases . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
This region contained a gene , Multiple Tumor Suppressor 1 ( MTS 1 ) , that encodes a previously identified inhibitor ( p 16 ) of cyclin dependent kinase 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
MTS 1 encodes p 16 , an inhibitor of cyclin dependent kinase 4 ( cdk 4 ) which complexes with cyclin D 1 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The multiple tumor suppressor 1 ( MTS 1 ) gene encoding the p 16 inhibitor of cyclin dependent kinase 4 is deleted or mutated in a wide variety of human tumor cell lines , but the importance of this gene as a tumor suppressor in vivo appears to be highly dependent on tumor type . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The recently cloned multiple tumor suppressor gene ( MTS 1 ) , the product of which interacts with CDK 4 to regulate cell growth , has been found to be mutated with high frequency in a variety of cell lines as well as primary tumors of different histologic types . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The oncoprotein cyclin D 1 binds to and activates cyclin dependent kinase 4 ( cdk 4 ) , whose activity is inhibited by p16INK4 , the product of the putative tumor suppressor gene MTS 1 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
A region of homology on human chromosome 9p21 22 that is frequently deleted in multiple human cancers has recently been found to contain a candidate tumor suppressor gene called multiple tumor suppressor 1 ( MTS 1 ) ; which was previously shown to encode an inhibitor of cyclin dependent kinase 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The role of alterations of the MTS 1 tumor suppressor gene on chromosome 9p21 , which encodes p 16 , the inhibitor of cyclin dependent kinase 4 and 6 , in tumorigenesis is not yet clear . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The frequencies of mutations in the adenomatous polyposis coli ( APC ) . p 53 , and p 16 ( MTS 1 ; multiple tumor suppressor 1 / CDK4I ; cyclin dependent kinase 4 inhibitor ) tumor suppressor genes were investigated in 23 oral squamous cell carcinomas ( SCCs ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The aim of the present study was to determine whether genetic alterations of p16INK4 ( MTS 1 ) and / or cyclin dependent kinase 4 ( CDK 4 ) occur in the genesis of these tumors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The gene MTS 1 encodes p16INK4 , an inhibitor of cyclin dependent kinase 4 , and is frequently deleted , mutated , or silenced by promoter methylation in melanoma cells and in the germline of familial melanoma patients . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
P 16 ( MTS 1 ) , an inhibitor of cdk 4 and cdk 6 , resides within the deleted 9p21 region in these tumors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Our data suggest that cyclin D decrease with melanoma terminal differentiation could be an alternative mode of growth arrest even in cells harbouring a mutant or transcriptionally silent cdk 4 inhibitor tumor suppressor p16ink4 gene . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p16Ink4 / MTS1 / CDKN2 is a cell cycle regulatory inhibitor of cyclin dependent kinase 4 ( cdk 4 ) , and a candidate tumour suppressor whose gene on chromosome band 9p21 is frequently deleted or mutated in diverse types of cancer . ^^^ Cdk 4 in association with its D type cyclin partners , together with p16Ink4 , and the product of the retinoblastoma tumour suppressor gene ( pRB ) , appear to constitute a G 1 phase controlling pathway which can become de regulated through oncogenic aberrations of any of the components . ^^^
Interacting proteins: Q8N726 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 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutations of p16Ink4 / CDKN2 and p15Ink4B / MTS2 genes in biliary tract cancers . p16Ink4 and p15Ink4B are cyclin dependent kinase 4 inhibitors and link to the regulation of cell cycle in mammalian cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The activity of CDK 4 is controlled by the opposing effects of the D type cyclin , an activating subunit , and p16INK4 , an inhibitory subunit . ^^^ Ectopic expression of p16INK4 blocked entry into S phase of the cell cycle induced by oncogenic Ha Ras , and this block was relieved by coexpression of a catalytically inactive CDK 4 mutant . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
We examined the genomic status of cyclin dependent kinase 4 and 6 inhibitors , p16INK4 , p15INK4B , and p 18 , in 40 primary lung cancers and 31 metastatic lung cancers . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The identification of a cdk 4 inhibitor , p16INK4 , as a target for mutations in cultured tumor lines and primary tumors suggested that RB activity may be affected in these cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Differential expression and cell cycle regulation of the cyclin dependent kinase 4 inhibitor p16Ink4 . p16Ink4 ( inhibitor of cyclin dependent kinase 4 ) is a cell cycle regulator that specifically binds to and inhibits Cdk 4 . ^^^ These results show a functional relationship between p16Ink4 and the retinoblastoma gene product and indicate that p16Ink4 is required for Cdk 4 inhibition only at the G 1 S transition at the time when Cdk 4 kinase activity is no longer necessary . . ^^^
Interacting proteins: Q8N726 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: Q8N726 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 . ^^^ Binding assays revealed that inhibition was invariably associated with p16INK4 binding to CDK 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 inhibitor gene ( p16INK4 ) has recently been mapped to chromosome 9p21 . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Immunohistochemical detection of CDK 4 and p16INK4 proteins in cutaneous malignant melanoma . p16INK4 gene , which encodes a specific inhibitor of cyclin dependent kinase 4 ( CDK 4 ) , has been recently reported as an important tumour suppressor gene . ^^^ To clarify any role for p16INK4 and CDK 4 proteins in the development of human malignant melanoma , we have examined , immunohistochemically , the expression of these two proteins in melanocytic neoplasms including 19 primary lesions of non familial melanoma . ^^^ Inverse expression of CDK 4 and p16INK4 , at individual cell level , was detected in one case of melanoma . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Alterations in P16ink4 or in the gene encoding one of its ligands , cyclin dependent kinase 4 ( CDK 4 ) , have been reported in human glioma cell lines and primary tumors but not in primitive neuroectodermal tumors ( PNETs ) , the most common malignant brain tumor of childhood . ^^^ In this study the authors have examined DNA from 20 primary PNETs in children and from 20 malignant astrocytomas to assess the frequency of P16ink4 and CDK 4 gene alterations associated with each type of tumor . ^^^ In total , nine astrocytomas ( 45 % ) exhibited homozygous P16ink4 deletion or CDK 4 gene amplification , but only one PNET ( 5 % ) demonstrated either gene alteration . ^^^ These results indicate that the incidence of P16ink4 and CDK 4 gene alterations in these two groups of tumors is different and suggest distinct pathogenetic etiologies may be associated with each neoplasm . . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Constitutive CDK 4 activity in melanomas may be the results of inactivation of the negative regulators known as CDK inhibitor p16INK4 , and / or p 21 ; and / or overexpression of cyclin D , the positive CDK 4 regulator . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In the present study , we analyzed human ovarian carcinoma cell lines for abnormalities in the tumor suppressor gene Rb ( retinoblastoma ) and in cyclin dependent kinase 4 ( CDK 4 ) inhibitor genes ( p16INK4 and p15INK4B ) using molecular biology techniques . ^^^ These data suggest that abnormalities of Rb and CDK 4 inhibitor genes ( p16INK4 , p15INK4B ) may be involved in human ovarian carcinogenesis . . ^^^ Analysis of the Rb gene and cyclin dependent kinase 4 inhibitor genes ( p16INK4 and p15INK4B ) in human ovarian carcinoma cell lines . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Immunohistochemical analysis of the expression of cdk 4 and p16INK4 in human endometrioid type endometrial carcinoma . ^^^ To obtain further information about the role of factors regulating the G 1 cell cycle in the development of endometrial carcinoma , the authors analyzed the expression of cdk 4 ( cyclin dependent kinase ) and p16INK4 ( an inhibitor of cdk 4 ) . ^^^ METHODS : Immunohistochemical staining was performed on 20 specimens of normal endometria and 41 specimens of endometrioid type endometrial carcinoma using antibodies against cdk 4 and p16INK4 . ^^^ RESULTS : In the glandular epithelia of the normal endometria , cytoplasmic staining of cdk 4 and p16INK4 was observed only in the proliferative phase , but nuclear staining of these agents was negligible . ^^^ In endometrial carcinomas , 8 ( 19 . 5 % ) and 14 ( 34 . 2 % ) were positive for cdk 4 and p16INK4 in the nucleus , respectively . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Endothelin 1 stimulated [ 3H ] thymidine incorporation , CDK 4 kinase activity , and the percent of cells in S phase were found to be significantly inhibited by overexpression of p16INK4 and slightly inhibited by overexpression of p21cip1 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
These include myc proto oncogene , 40S ribosomal protein S 19 , heat shock proteins , leukosialin S ( CD 43 ) , integrin alphaL ( CD11A ) , calgranulin ( A ) , and CDK 4 inhibitor ( p16ink4 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In the present study it is shown that this results from p16INK4 mediated dissociation of the complex cdk 4 cyclin D 1 , which is responsible for the inactivation of the gate keeper of G 1 S transition , the retinoblastoma protein pRb . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
BACKGROUND : The p16INK4 ( MTS1 / CDNK2A ) gene , located on chromosome 9p21 , is an inhibitor of cyclin dependent kinase 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin dependent kinase 4 , and its homologous deletion is common in human breast cancer . p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain , lung , prostate , and esophageal cancers . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
It is widely known that P16INK4a can arrest cells in the G 1 phase , but how the expression of exogenous P16INK4 gene can affect the activity of Cdk 4 Cyclin D 1 remains unclear . ^^^
Interacting proteins: Q8N726 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: Q8N726 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 . . ^^^ Alterations of cyclin dependent kinase 4 inhibitor ( p16INK4A / MTS1 ) gene structure and expression in acute lymphoblastic leukemias . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
A p16INK4a insensitive CDK 4 mutant targeted by cytolytic T lymphocytes in a human melanoma . ^^^ The mutation , an arginine to cysteine exchange at residue 24 , was part of the CDK 4 peptide recognized by CTLs and prevented binding of the CDK 4 inhibitor p16INK4a , but not of p 21 or of p27KIP1 . ^^^ These results suggest that mutation of CDK 4 can create a tumor specific antigen and can disrupt the cell cycle regulation exerted by the tumor suppressor p16INK4a . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The COOH terminal region of p16INK4a is not required for the protein to bind and to inhibit CDK 4 , but the deletion of the 4th ankyrin repeat abolished the activity completely . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Germline mutations in the p16INK4a binding domain of CDK 4 in familial melanoma . ^^^
Interacting proteins: Q8N726 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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
We examined the genomic status of the p16INK4A ( inhibitor of cyclin dependent kinase 4 A ) and cyclin dependent kinase 4 ( CDK 4 ) genes in 62 human hepatocellular carcinomas ( HCCs ) , 5 cholangiocellular carcinomas and 6 cell lines derived from human liver cancers . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p16INK4a was isolated as a gene which binds and inhibits the cyclin dependent kinase 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
As the genes encoding the CDK 4 and CDK 6 inhibitors ( CDK4 / 6 inhibitors ) p16INK4A / CDKN2 / MTS1 and p15INK4B / MTS2 have been found to be altered in many cancer cell lines and primary neoplastic tissues , CDK inhibitors in general and CDK4 / 6 inhibitors in particular are now a se : of candidate tumor suppressors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Immunocomplex kinase assays with cyclin dependent kinase 4 antiserum indicate that Tax blocks the inhibition of cdk 4 kinase activity by p16INK4a . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Expression of p16INK4a suppresses the unbounded and anchorage independent growth of a glioblastoma cell line that lacks p16INK4a . p16INK4a is a inhibitory protein of Cyclin dependent kinase 4 ( Cdk 4 ) . p16 negatively regulates the cell cycle progression from G 1 to S phase . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p16INK4A gene , which encodes the cell cycle regulatory protein cyclin dependent kinase 4 inhibitor , is a putative tumor suppressor gene . ^^^
Interacting proteins: Q8N726 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 . ^^^ We found that status of p 107 , p 130 , p15INK4b , p18INK4c , p21Cip1 , p27Kip1 , cyclin D 1 , and Cdk 4 were not correlated with the growth inhibitory activity of exogenous p16INK4a . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
In human cells transformed by the large T antigen of simian virus 40 ( SV 40 T Ag ) and human tumour cell lines that lack a functional retinoblastoma gene product ( pRb ) no cyclin D 1 Cdk4 complexes can be detected because all the available Cdk 4 is associated with the Cdk inhibitor p16INK4a . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The mammalian cell cycle is controlled by regulators of the G 1 to S transition such as tumor suppressor proteins , p 53 and retinoblastoma ( RB ) ; cyclin D 1 and cyclin dependent kinase 4 ; and inhibitor of cyclin dependent kinase , p16INK4A . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutations in Rb , cyclin D 1 , its catalytic subunit Cdk 4 , and the CDKI p16Ink4a , which alter the protein or its level of expression , are all strongly implicated in cancer . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Prognostic implications of cyclins ( D 1 , E , A ) , cyclin dependent kinases ( CDK 2 , CDK 4 ) and tumor suppressor genes ( pRB , p16INK4A ) in childhood acute lymphoblastic leukemia . ^^^ Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias ( ALL ) for their expression of cyclins ( D 1 , E , A ) , cyclin dependent kinases ( cdk 2 , cdk 4 ) and tumor suppressor genes ( pRb , p16INK4A ) , in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Role of CDK 4 and p16INK4A in interleukin 6 mediated growth of multiple myeloma . ^^^ We therefore examined the kinetics of cyclin dependent kinase 4 ( CDK 4 ) , p16INK4A , and pRB activation during IL 6 mediated patient MM cell growth compared with growth of IL 6 unresponsive patient plasma cell leukemia ( PCL ) cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The tumor suppressor protein p16INK4a ( inhibitor of CDK 4 ) is one of the most direct links between cell cycle control and cancer . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 and P11802	Pubmed	SVM Score :0.0
The gene of the cyclin dependent kinase 4 ( CDK 4 ) inhibitor p16INK4A ( CDKN2 / MTS1 ) has been proposed as a candidate for a tumor suppressor gene located on chromosome 9p21 , a frequently deleted region in a series of human cancers including malignant melanoma . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Others have shown that a specific mutation in the NH 2 terminal region of the CDK 4 gene product can disrupt p16INK4a binding , thereby bypassing its inhibitory activity . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The resulting growth inhibitory effect of HMBA was completely reversible and was analyzed in terms of percent cells in G 1 ; association of D type cyclins with cyclin dependent kinase ( cdk ) 4 and cdk 6 ; G 1 kinase activity ; association of retinoblastoma protein ( pRb ) and phosphorylated pRb with D type cyclins ; and association of p16INK4a , p15INK4b , and p27Kip1 with cdk 4 and cdk 6 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The expression of cyclin D 1 , cdk 4 , p16INK4a , and Rb protein was examined by immunohistochemistry in 4 ( methylnitrosamino ) 1 ( 3 pyridyl ) 1 butanone ( NNK ) induced mouse lung tumors . ^^^ These results suggest that alterations in the cell cycle proteins , cyclin D 1 , cdk 4 , p16INK4a , and Rb , may play a role in the acquisition of autonomous growth by adenomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The solution structure of the tumor suppressor p16INK4A has been determined by NMR , and important recognition regions of both cdk 4 and p16INK4A have been identified . ^^^ A fragment of 58 residues at the N terminus of cdk 4 important for p16INK4A binding has been identified . ^^^ Tumor suppressor p16INK4A : determination of solution structure and analyses of its interaction with cyclin dependent kinase 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Several regulators of E2F transcriptional activity , including the retinoblastoma tumor suppressor ( Rb ) protein , p16Ink4a , cyclin D 1 , and cyclin dependent kinase 4 , have been shown to be targets for genetic alterations that underlie the development of human cancers . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
However , we have also found that hormone treated cells actually show more p16INK4A inhibitor associated with another kinase , Cdk 4 , as the cells are entering S phase . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Identification of the critical residues involved in the interaction explains how mutations in Cdk 4 and p16INK4a result in loss of kinase inhibition and cancer . . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Analysis of cell cycle regulators : p16INK4A , pRb , and CDK 4 in low and high grade meningiomas . ^^^ Abnormalities in the p16INK4A , CDK 4 , and Rb genes , which regulate transition through G 1 phase of the cell cycle , have been implicated in the progression of diverse types of cancer . ^^^ To evaluate the involvement of p16INK4A , CDK 4 , and Rb in the tumorigenesis of meningiomas , the status of these genes or gene products were examined . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Loss of function of p15INK4b and p16INK4a ( multiple tumor suppressor 1 and CDK 4 inhibitor ) determines impairment in the control of the cell cycle and contributes to the transformation of several cell types . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
When MAPK was activated in wild type mouse hepatocytes for 24 h , via infection with a construct to express an inducible oestrogen receptor Raf 1 fusion protein ( DeltaRaf : ER ) , the expression of p21Cip 1 / WAF1 and p16INK4a CKI proteins increased , cyclin dependent kinase 2 ( cdk 2 ) and cdk 4 activities decreased , and DNA synthesis decreased . ^^^ When MAPK was activated in p16INK4a null hepatocytes for 24 h , the expression of p21Cip 1 / WAF1 increased , cdk 2 and cdk 4 activities decreased and DNA synthesis decreased . ^^^ In contrast with these findings , prolonged activation of the MAPK pathway in hepatocytes from p21Cip 1 / WAF1 null mice enhanced cdk 2 and cdk 4 activities and caused a large increase in DNA synthesis , despite elevated expression of p16INK4a . ^^^ Expression of anti sense p21Cip 1 / WAF1 in either wild type or p16INK4a null hepatocytes decreased the ability of prolonged MAPK signalling to increase the expression of p21Cip 1 / WAF1 , and permitted MAPK signalling to increase both cdk 2 and cdk 4 activities and DNA synthesis . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Among the cell cycle related proteins we analyzed , only p21waf1 bcl 2 and CDK 4 were significantly and positively correlated to p16ink4a . ^^^ An enhancement of p16ink4a , p21waf1 and bcl 2 was previously described in prolonged cellular survival , while aging cells showed a decrease in CDK 4 expression . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In contrast , mice expressing a mutant Cdk 4 that can not bind the cell cycle inhibitor P16INK4a display pancreatic hyperplasia due to abnormal proliferation of beta islet cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutational analysis of the N ras , p 53 , p16INK4a , CDK 4 , and MC1R genes in human congenital melanocytic naevi . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
In contrast , the expressions of other cell cycle regulated genes and proto oncogene , including the cyclin dependent kinase 4 ( cdk 4 ) , retinoblastoma , p16INK4a and p21H ras , were not altered . ^^^
Interacting proteins: Q8N726 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: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
This resistance is associated with low expression of p15ink4b and p16ink4a , constitutive Rb phosphorylation and high levels of cdk 4 and cdk 2 kinase activity . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Over expression of cdk 4 , especially a variant which can not bind p16INK4a , overcame cell cycle inhibition resulting from activation of KRAB AML 1 ER , although cdk 4 did not accelerate proliferation when expressed alone . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In this study , we show that BMP 2 did not alter expression of cyclin D , cyclin E , cyclin dependent kinase 2 ( CDK 2 ) , CDK 4 , p27KIP1 , p16INK4a , or p15INK4b , but enhanced expression of p 21 ( CIP1 / WAF1 ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Previous studies have shown more than 50 % of primary GBM tumours contain either complete loss of the p16INK4a locus or amplification of the CDK 4 gene . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
In these cells , senescence is associated with increased binding of p16INK4a to CDK 4 and loss of E2F binding activity . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The p16ink4a cyclin D1 / cyclin dependent kinase 4 ( Cdk 4 ) retinoblastoma ( Rb ) pathway has emerged as a critical target in oncogenesis . ^^^ Expression of p16ink4a , cyclin D 1 , Cdk 4 , and Rb in relation to that of proliferating cell nuclear antigen was characterized in esophagi by immunohistochemistry at 0 , 24 , and 48 h , and 1 , 3 , 7 , 10 , and 14 weeks after NMBA treatment . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Analysis of tumor derived mutations has led to the suggestion that p16INK4a , cyclin D 1 , cdk 4 , and the retinoblastoma protein ( pRB ) are components of a regulatory pathway that is inactivated in most tumor cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The re expressed p16INK4A was functional , because it bound to and inhibited CDK 4 kinase activity , and increased the concentrations of the hypophosphorylated form of retinoblastoma protein ( pRB ) in cells with a wild type RB gene . ^^^ The inactivation of the cyclin dependent kinase 4 and 6 ( CDK4 / 6 ) inhibitor p16INK4A may be caused by gene deletion , mutation or promoter hypermethylation . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Inactivation of p16INK4a and / or activation of cyclin dependent kinase 4 ( CDK 4 ) are strongly associated with both susceptibility and progression in melanoma . ^^^ Activating CDK 4 mutations prevent the binding and inhibition of CDK 4 by p16INK4a . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Concomitantly , p27Kip1 ( where Kip is kinase inhibitory protein ) was induced markedly , whereas other negative cell cycle regulators , such as p21Cip1 ( where Cip is cyclin dependent kinase interacting protein ) , p15INK4B and p16INK4A ( where INK is inhibitors of cyclin dependent kinase 4 ) , were not , implying its association in the G 1 arrest . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
The effect of exposure to 50 Hz , 1 mT magnetic fields ( MF ) on the cell cycle in general , on the DNA synthesis in S phase , and on the G 1 phase regulating proteins Cdk 4 , cyclin D 1 , p16INK4a , and p21CIP1 was investigated in human amniotic fluid cells . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
To improve understanding of the role of this pathway in spermatogenesis , and its subversion in TGCTs , we examined immunohistochemical expression patterns of CDK 4 , p16INK4a , p15INK4b , and pRB , and established an in situ assay for cyclin D mediated phosphorylation of serine 795 , a phosphorylation event critical for neutralization of pRB ' s growth restraining ability . pRB was expressed throughout adult spermatogenesis and was detectable in teratomas , but was absent or grossly reduced in carcinoma in situ ( CIS ) and most seminomas and embryonal carcinomas . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
An intriguing novel observation was that p16INK4A inactivation was associated with increased expression of cdk 4 , a kinase target of p16INK4A inhibitory function . ^^^ This could indicate the existence of a regulatory feedback loop between p16INK4A and cdk 4 . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Aberrant p16INK4A RNA transcripts expressed in hepatocellular carcinoma cell lines regulate pRb phosphorylation by binding with CDK 4 , resulting in delayed cell cycle progression . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
Biophys . 41 , 131 ] , this study aims to document the influence of 50 Hz , 1 mT magnetic fields ( MF ) , with or without initial gamma ionizing radiation ( IR ) , on the following cell proliferation relevant parameters in human amniotic fluid cells ( AFC ) : cell cycle distribution , expression of the G 1 phase regulating proteins Cdk 4 , cyclin D 1 , p21CIP1 and p16INK4a , and Cdk 4 activity . ^^^
Interacting proteins: Q8N726 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: Q8N726 and P11802	Pubmed	SVM Score :0.0
After 90 day feeding , bladder samples were collected for histopathological diagnoses , and immunohistochemical method was used to characterize the expression of p16Ink4a cyclin D 1 , CDK 4 , EGFr and cyclin E in relation to that of proliferating cell nuclear antigen ( PCNA ) . ^^^ Overexpressions of cyclin D 1 , CDK 4 , EGFr are found in the corresponding lesion . p16Ink4a nuclear staining reduced in proliferative bladders especially with a great quantity of stone . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Protein expression of cyclin D 1 and cyclin dependent kinase 4 ( Cdk 4 ) , but not p16INK4a Cdk inhibitor in the tumor was significantly reduced by vitamin K 2 or K 3 treatment , indicating that vitamins K 2 and K 3 may induce G 1 arrest of cell cycle on PLC / PRF / 5 cells in vivo . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Although protein expression levels of cyclin D 1 and p16INK4a cyclin dependent kinase ( Cdk ) inhibitor in HCC tumors were not decreased by vitamin K 5 treatment , those of Cdk 4 were reduced significantly by the treatment . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Several antigens were assessed immunohistochemically ( pRb 1 , p16INK4A , cyclin D 1 , cdk 4 , estrogen receptor ( ER ) , progesterone receptor ( PR ) , androgen receptor ( AR ) , p 53 , Ki 67 , p27KIP1 , PTEN , hMLh 1 , phospho AKT , collagen 4 , leptin and CD 90 ) in both tumors . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Mutational and methylation analysis of the cyclin dependent kinase 4 inhibitor ( p16INK4A ) gene in chronic lymphocytic leukemia . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
However , overexpression of Id 1 had no effect on the pRB , CDK 4 and p16INK4A expressions . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Many mechanisms may be responsible for activating the RB Cyclin D 1 pathway , including activating ( CDK 4 ) and inactivating mutations ( p16INK4A ) , deletions ( RB and p16INK4A ) , amplifications ( CCND 1 and CDK 4 ) , silencing methylation ( p16INK4A and RB ) , and hyper phosphorylation ( RB ) . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
Here , we report that CDK 4 complexes from Nalm 6 extracts phosphorylated in vitro the CDK 2 preferred serine 612 , which was inhibited by p16INK4a , and fascaplysin . ^^^
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q8N726 and P11802	Pubmed	SVM Score :0.0
NA