Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :1.1383608
In mouse MEL erythroleukemia cells , p16INK4a associates preferentially with cdk 6 under conditions where cdk 4 and cdk 6 are coexpressed at equivalent levels . 1.1383608^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Moreover , D type cyclin dependent kinase activity specifically activates the E2F 1 promoter by relieving E2F mediated repression but is inhibited by coexpression of the cdk 4 and cdk 6 inhibitor p 16 ( CDKN 2 , MTS 1 , INK 4 ) . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated mouse skin tumors . p16INK4a and p15INK4b are cell cycle regulators that specifically bind to and inhibit the cyclin D dependent kinases , cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Since most hematological malignancies except ALL are infrequently associated with p16INK4A and retinoblastoma ( Rb ) gene alteration it seems worthwhile to explore cdk 4 and cdk 6 expression to determine whether or not the disruption of the p16INK4A / Rb / cdk4 / cdk6 regulatory loop might play a role in their pathogenesis . . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Novel INK 4 proteins , p 19 and p 18 , are specific inhibitors of the cyclin D dependent kinases CDK 4 and CDK 6 . ^^^ Two novel members of the mouse INK 4 gene family , p 19 and p 18 , that specifically inhibit the kinase activities of CDK 4 and CDK 6 , but do not affect those of cyclin E CDK 2 , cyclin A CDK 2 , or cyclin B CDC 2 , were isolated . ^^^ Like the previously described human INK 4 polypeptides , p16INK4a / MTS1 and p15INK4b / MTS2 , mouse p 19 and p 18 are primarily composed of tandemly repeated ankyrin motifs , each ca . 32 amino acids in length , p 19 and p 18 bind directly to CDK 4 and CDK 6 , whether untethered or in complexes with D cyclins , and can inhibit the activity of cyclin D bound cyclin dependent kinases ( CDKs ) . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Normal progression through G 1 is promoted by the activity of the cyclin dependent protein kinases CDK 4 and CDK 6 ( ref . 2 ) , which are inhibited by the protein p16INK4 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Multiple mechanisms of p16INK4A inactivation in non small cell lung cancer cell lines . p16INK4A , a specific inhibitor of cyclin dependent kinase ( cdk ) 4 and cdk 6 , is a candidate tumor suppressor in malignancies with wild type retinoblastoma ( Rb ) . ^^^ Although this variant formed complexes with cdk 4 and cdk 6 , it had a profoundly reduced half life , producing low steady state levels of p16INK4A and abundant levels of free cdks . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The INK4a ( MTS 1 , CDKN 2 ) gene encodes an inhibitor ( p16INK4a ) of the cyclin D dependent kinases CDK 4 and CDK 6 that blocks them from phosphorylating the retinoblastoma protein ( pRB ) and prevents exit from the G 1 phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
DIA / LIF stimulated ES cells are not growth arrested by overexpression of p16Ink4a , a specific inhibitor of CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Progression through the G 1 phase of the cell cycle is dependent on the activity of holoenzymes formed between D type cyclins and their catalytic partners , the cyclin dependent kinases cdk 4 and cdk 6 . p16INK4a , p15INK4b , and p18INK4c , a group of structurally related proteins , function as specific inhibitors of the cyclin D dependent kinases and are likely to play physiologic roles as specific regulators of these kinases in vivo . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 ( CDK 4 ) and CDK 6 and control cellular proliferation by preventing entry into the S phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Biochemical studies suggest that p16INK4 mediates its effects by specifically inhibiting the G 1 cyclin dependent kinases CDK 4 and CDK 6 , thereby regulating the progression through G 1 into S phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Here , we found that Tax binds to a cyclin dependent kinase inhibitor , p16INK4A , which has ankyrin motifs similar to 1 kappa B . p16INK4A binds to the cyclin dependent kinases , CDK 4 and CDK 6 , and inhibits their activity , resulting in suppression of G 1 phase progression . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Relative mRNA expression levels were assessed using a rapid and sensitive Reverse Transcriptase Polymerase Chain Reaction ( RT PCR ) assay called the `` Primer dropping ' ' method . p16INK4 , a specific inhibitor of the cyclin D associated kinases CDK 4 and CDK 6 , was , in addition to p 21 and cyclin D 1 , overexpressed in higher passage cells , while the abundance of the D type kinase mRNAs remained relatively constant . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Recent studies have identified different CDK inhibitory genes ( CDKis ) , and two of them , p16ink4a / MTS1 / CDKN2 and p15ink4b / MTS2 are both mapped to chromosome 9p21 and inhibit cyclin D CDK 4 and CDK 6 complexes . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
In the glioblastomas with no alterations of CDKN2A , CDK 4 or RB 1 , several other genes ( CCND 1 , CCND 2 , CCND 3 , CDK 6 , E2F , CDK 7 , MYC and MYCN ) whose products take part in cell cycle regulation were examined . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Recently , two cell cycle regulators that inhibit the cyclin D 1 associated kinases cdk 4 and cdk 6 have been identified : p 16 and p 15 , the products of the INK4A ( also known as CDKN 2 , MTS 1 ) and INK4B ( also known as MTS 2 ) putative tumor suppressor genes located on 9p21 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The first group , including p16Ink4a , p15Ink4b , p18Ink4c and p19Ink4d , is specific for the G 1 CDKs , CDK 4 and CDK 6 , inhibiting the kinase activity of cyclin D / CDK4 CDK 6 complexes on pRb . p16Ink4a , down regulated by pRb , inhibits G 1 CDKs by competition with cyclin D ; p15Ink4b , the synthesis of which is induced by TGF beta , seems to be a mediator of TGF beta mediated cell cycle arrest . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The p16INK4 family of CDK inhibitors specifically prevent the phosphorylation of the retinoblastoma susceptibility gene product , pRb , by inhibiting the kinase activity of CDK 4 and CDK 6 , thereby keeping pRb in its active form as a growth suppressor . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NMR structural characterization of the CDK inhibitor p19INK4d . p19INK4d is a 165 amino acid protein that belongs to the INK 4 family of CDK 4 and CDK 6 inhibitors . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Effects of exogenous p16INK4a on growth of cells with various status of cell cycle regulators . p16INK4a , a protein that inhibits cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , is deficient in many human cancers and in established lines of tumor cells . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Here , we found that Tax binds to a cyclin dependent kinase inhibitor , p16Ink4a . p16Ink4a binds to cyclin dependent kinases , CDK 4 and CDK 6 , and inhibits their activity , resulting in suppression of G 1 phase progression . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Analysis of expression of genes regulating Rb phosphorylation revealed that activin A suppressed cyclin D 2 , the sole D type cyclin gene expressed in the hybridoma cells , and activated p21CIP1 / WAF1 but had no effect on expression of cyclin dependent kinases ( CDK 2 , CDK 4 , CDK 6 ) and other CDK inhibitors ( p27KIP1 , p16INK4a , p15INK4b ) . ^^^
Interacting proteins: Q00534 and P42771	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 . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Both viral cyclins form active kinase complexes with Cdk 6 that are resistant to inhibition by the CDK inhibitors p 16 ( Ink4a ) , p21Cip1 and p27Kip1 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The p16 / MTS1 / CDKN2 gene on human chromosome band 9p21 encodes two unrelated proteins : p16INK4a , a specific inhibitor of the cyclin D dependent kinases CKD 4 and CDK 6 , and the structurally unrelated p19ARF protein that arrests cell growth in G1 / S and also in G2 / M . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Inactivation of p16INK4 , an inhibitor of cyclin dependent kinases 4 ( CDK 4 ) and 6 ( CDK 6 ) , may be essential for oncogenesis in non small cell lung cancer ( NSCLC ) . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
CDK 6 is one of the targets of p 16 and p 15 , CDK inhibitors encoded by MTS 1 and MTS 2 , two tumor suppressor genes that are frequently deleted in T cell leukemia . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
The INK4a ARF locus encodes two unrelated proteins that both function in tumor suppression . p16INK4 binds to and inhibits the activity of CDK 4 and CDK 6 , and ARF arrests the cell cycle in a p 53 dependent manner . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
In addition , CDK 6 was not present in p16INK4a immune complexes in cells with significant kinase activity , although p16INK4a levels were high . ^^^ The CDK 6 gene from each cell line was examined for mutations that might affect p16INK4a binding , whereas p16INKa add back experiments were performed with CDK 6 immune complexes to assess p16INK4a function . ^^^ A bona fide CDK 6 mutation that disrupts p16INK4a binding and prevents inhibition of CDK 6 protein kinase activity was identified in 1 of 17 neuroblastoma cell lines . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
The product of the alpha transcript , p 16 ( INK4a ) , is a recognized tumour suppressor that induces a G 1 cell cycle arrest by inhibiting the phosphorylation of the retinoblastoma protein by the cyclin dependent kinases , CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
The structures of Cdk 6 bound to p16INK4a and to the related p19INK4d reveal that the INK 4 inhibitors bind next to the ATP binding site of the catalytic cleft , opposite where the activating cyclin subunit binds . ^^^ Structural basis for inhibition of the cyclin dependent kinase Cdk 6 by the tumour suppressor p16INK4a . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	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 . ^^^ INK4a , a critical element of the retinoblastoma gene pathway , binds to and inhibits the activities of CDK 4 and CDK 6 , while ARF , a critical element of the p 53 pathway , increases the level of functional p 53 via interaction with MDM 2 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
BACKGROUND : The four members of the INK 4 gene family ( p 16 ( INK4a ) , p 15 ( INK4b ) , p 18 ( INK4c ) and p 19 ( INK4d ) ) inhibit the closely related cyclin dependent kinases CDK 4 and CDK 6 as part of the regulation of the G 1 > S transition in the cell division cycle . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The tumour suppressor p 16 is a member of the INK 4 family of inhibi tors of the cyclin D dependent kinases , CDK 4 and CDK 6 , that are involved in the key growth control pathway of the eukaryotic cell cycle . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Here we show that although all four INK 4 proteins associate with CDK 4 and CDK 6 in vitro , only p 16 ( INK4a ) can form stable , binary complexes with both CDK 4 and CDK 6 in proliferating cells . ^^^ The other INK 4 family members form stable complexes with CDK 6 but associate only transiently with CDK 4 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
As expected , induction of p 16 ( INK4a ) results in a G 1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein ( pRb ) by the cyclin dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Furthermore , CDK 6 was also strongly expressed in the group of cases with high p16ink4a level . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
One of the cell lines , SCC 4 , contains a cdk 6 amplification and expresses functional p16ink4a , the other cell lines express undetectable levels of p16ink4a , despite a lack of coding region mutations . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Restoration of p16INK4A protein induces myogenic differentiation in RD rhabdomyosarcoma cells . p16INK4A ( p 16 ) tumour suppressor induces growth arrest by inhibiting function of cyclin dependent kinase ( CDK ) 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The cdk 6 protein is found to suppress p 16 ( INK4a ) mediated inhibition of spreading and is also shown to localize to the ruffling edge of spreading cells , indicating a function for cdk 6 in controlling matrix dependent cell spreading . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Functional analysis showed that the proline 18 / isoleucine 51 p16INK4a variant was diminished in cdk 6 binding , cdk 6 inhibition and NIH / 3T3 fibroblast growth suppression compared with the histidine 18 / valine 51 variant , whereas both of the p19ARF variants suppressed growth with similar potencies . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
To understand the structural basis for the 5 cyclin specificity for CDK 6 and the insensitivity of the complex to inhibitors of the p 21 and INK 4 families , a 5 cyclin CDK 2 model was built on the basis of the known structures of human cyclin A in complex with CDK 2 and the CDK inhibitor p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Among the 17 sequence variants analysed , three distinct categories can be distinguished : those that abrogate the binding of p16INK4a to CDK 4 and CDK 6 , those that alter the properties of the protein without preventing it from interacting with CDKs , and those that have no discernible effect on protein function . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Furthermore , a mutation that prevents cdk 6 interaction with INK 4 proteins ( cdk6R31C ) was found to inactivate the proliferative effect of cdk 6 and increase cytoplasmic localization , despite the fact that this mutant could phosphorylate the retinoblastoma protein in vitro . ^^^ Although it is clear that cdk 4 can act as an oncogene at least in part by evading inhibition by p 16 ( INK4a ) , the role of cdk 6 in tumorigenesis is less well understood . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The p 16 ( INK4a ) tumor suppressor inhibits cyclin dependent kinases ( CDK 4 and CDK 6 ) . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The INK 4 family of cyclin dependent kinase ( CDK ) inhibitors includes four 15 to 19 kDa polypeptides ( p 16 ( INK4a ) , p 15 ( INK4b ) , p 18 ( INK4c ) , and p 19 ( INK4d ) ) that bind to CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The INK4A gene , a candidate tumor suppressor gene located on chromosome 9p21 , encodes two protein products , p 16 and p 19 ( ARF ) . p 16 is a negative cell cycle regulator capable of arresting cells in the G 1 phase by inhibiting cyclin dependent kinases 4 ( Cdk 4 ) and 6 ( Cdk 6 ) , thus preventing pRB phosphorylation . p 19 ( ARF ) prevents Mdm 2 mediated neutralization of p 53 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The molecular events that lead to melanoma cell autonomous growth are not well defined , but are likely to include sustained activity of cyclin dependent kinases ( CDK 2 , CDK 4 and CDK 6 ) as a result of loss of CDK inhibitors ( such as p16INK4a and possibly p27KIP1 ) , and persistent upregulation of several cyclins ( cyclin D 1 , cyclin A and cyclin E ) , the positive regulators of CDKs . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
We report that the INK 4 proteins share the ability to arrest cells in G 1 , and interact with CDK 4 or CDK 6 with similar avidity . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
A tumor suppressor gene , p 16 ( INK 4 ) , which is deleted or mutated in tumors , regulates cell cycle progression through a G ( 1 ) S restriction point by inhibiting CDK 4 ( CDK 6 ) / cyclin D mediated phosphorylation of pRb . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
D 1 , p16INK4a and pRb expression in resectable non small cell lung cancer . p 21 ( p21WAF1 / CIP1 ) is involved in cell cycle regulation , as an inhibitor of cyclin dependent kinases ( CDK 2 , CDK 4 and CDK 6 ) . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Progression to senescence was accompanied by a progressive increase in both the level of p 16 ( INK4A ) and in its association with cdk 4 and cdk 6 . ^^^ As HPECs approached senescence , cdk 4 and cdk 6 bound p 16 ( INK4A ) showed a shift to a slower mobility due to a change in its phosphorylation profile . ^^^ As p 16 ( INK4A ) increased in cdk 4 and cdk 6 complexes , there was a loss of cyclin D 1 binding . ^^^ The altered phosphorylation of p 16 ( INK4A ) in senescent prostatic epithelial cells may facilitate its association with cdk 4 and cdk 6 and play a role in the inactivation of these kinases . . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
However , RA had no effect on the levels of cyclins A , D 1 , D 3 , E , or H , or on Cdk 2 , Cdk 4 , Cdk 5 , CDk 6 , Cdk 7 , p 16 ( Ink4A ) , p 15 ( Ink4B ) , p 53 , or pRb proteins in CH 27 cells . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
We did not observe consistent changes in protein levels of cyclin D , cyclin E , CDK 4 , CDK 6 , CDK 2 , p 27 ( Kip 1 ) , p 16 ( INK4a ) , or RNA levels of p 15 ( INK4b ) . ^^^
Interacting proteins: Q00534 and P42771	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 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
We found that the expression of cyclin A and p 21 ( WAF 1 ) molecules was primarily modulated by TGFbeta 1 treatment while the expression of other regulatory components , like cyclins D , cyclin E , cdk 2 , cdk 4 , and cdk 6 or p 15 ( INK4B ) , p 16 ( INK4A ) , and p 27 ( KIP 1 ) was not significantly affected . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Here we present the 2 . 9 A crystal structure of the inactive ternary complex between Cdk 6 , the INK 4 inhibitor p 18 ( INK4c ) , and a D type viral cyclin . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The 113insArg mutant p 16 ( INK4a ) was unable to bind cdk 4 and cdk 6 in an in vitro binding assay . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
We screened a cohort of 206 patients with clinically localized PC treated with radical prostatectomy for overexpression of the INK4A gene , the product of which inactivates the G 1 phase cyclin dependent kinases , Cdk 4 and Cdk 6 . p16INK4A protein expression was evaluated by immunohistochemistry in areas of high grade intraepithelial neoplasia ( HGPIN ) , a precursor to invasive disease , and of cancer in the same specimen . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Rb phosphorylation is mediated by cyclin dependent kinases ( CDKs ) , whose activity is enhanced by cyclins and inhibited by CDK inhibitors . p 16 ( INK4A ) is a member of a family of inhibitors specific for CDK 4 and CDK 6 . p 16 ( INK4A ) is deleted and inactivated in a wide variety of human malignancies , including familial melanomas and pancreatic carcinoma syndromes , indicating that it is an authentic human tumor suppressor . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
While members of the INK 4 family ( p16INK4A , p15INK4B , p18INK4C , p19INK4D ) interact specifically with CDK 4 and CDK 6 , the CIP / KIP inhibitors p21CIP1 / WAF1 , p27KIP1 and p57KIP2 inhibit a broader spectrum of CDK . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The amount of p16INK4A , p21CIP1 , p18INKAC and CDK 6 was variable from one cell line to the other . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
This KSHV cyclin activates CDK 6 , alters its substrate specificity , and renders CDK 6 insensitive to inhibition by the cdk inhibitor p 16 ( INK4a ) . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
This phenomenon shows an increased expression of growth cell inhibitors : p21Waf1 described as an universal CDK inhibitor and p16INK4a as a specific inhibitor for both G 1 phase kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Aberrations in the MTS 1 tumor suppressor locus in oral squamous cell carcinoma lines preferentially affect the INK4A gene and result in increased cdk 6 activity . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Cdkn2a became a primary candidate for Papg 1 for two reasons : ( 1 ) two haplotypes of mouse Cdkn2a were found to segregate with differential genetic susceptibility to lung tumor progression in mice ; and ( 2 ) in vitro studies showed that the p 16 ( INK4a ) allele from the BALB / cJ mouse had a significantly decreased ability to bind and inhibit CDK 6 and to suppress cell growth when compared with the p 16 ( INK4a ) allele from the A / J mouse . ^^^ Cdkn2a became a primary candidate for Papg 1 for two reasons : ( 1 ) two haplotypes of mouse Cdkn2a were found to segregate with differential genetic susceptibility to lung tumor progression in mice ; and ( 2 ) in vitro studies showed that the p 16 ( INK4a ) allele from the BALB / cJ mouse had a significantly decreased ability to bind and inhibit CDK 6 and to suppress cell growth when compared with the p 16 ( INK4a ) allele from the A / J mouse . ^^^
Interacting proteins: Q00534 and P42771	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 . ^^^ Most of the key interactions observed , were already anticipated in the analysis of the crystal structure of Cdk 6 p16 ( INK4a ) . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Cyclin K resists the actions of the p 16 INK4a and p27Kip1 inhibitors and extends the range of cdk 6 substrates , thereby inducing cell cycle progression toward S phase . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Moreover , UV induced melanomas showed a strict reciprocal relationship between cdk 6 amplification and p 16 ( INK4a ) loss , which is consistent with the actions of UV along the Rb pathway . ^^^ In a melanoma model driven by H RAS activation and loss of p 19 ( ARF ) function , UV exposure resulted in a marked acceleration in melanoma genesis , with nearly half of these tumors harboring amplification of cyclin dependent kinase ( cdk ) 6 , whereas none of the melanomas arising in the absence of UV treatment possessed cdk 6 amplification . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The INK 4 family of cyclin dependent kinase ( CDK ) inhibitors negatively regulates cyclin D dependent CDK 4 and CDK 6 and thereby retains the growth suppressive function of Rb family proteins . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
To study the molecular mechanisms of cell cycle regulation by AESR , we also measured the intracellular levels of cell cycle regulatory proteins such as cyclin D , cyclin dependent kinases ( CDK ) 4 , CDK 6 , cyclin E , CDK 2 , p 53 , p21WAF1 / CIP1 and p16INK4A . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Our data suggest that Cdk 6 cyclin D 3 activity in other cell types , including tumors , may also be refractory to p 16 mediated growth inhibition and raises the possibility of additional specificity within the INK 4 family . . ^^^ Cdk 6 cyclin D 3 activity in murine ES cells is resistant to inhibition by p 16 ( INK4a ) . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
In rasREF cells treated with DE for 72 h in suspension culture ( a ) , the levels of cyclin D 1 , cyclin A , p 27 ( Kip 1 ) , and hyperphosphorylated Rb were decreased , but the levels of cdk 4 , cdk 6 , cdk 2 , p 16 ( INK4a ) , and p 21 ( Cip 1 ) were not affected . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Wild type p16INK4a suppresses cell growth , telomerase activity and DNA repair in human breast cancer MCF 7 cells . p16INK4a , a cell cycle inhibitor that inhibits cyclin dependent kinase 4 ( cdk 4 ) and cdk 6 , has been found as the tumor suppressor gene and is frequently deleted , methylated or mutated in many malignancies . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
The CDKN2A gene , located on chromosome 9p21 , encodes the tumour suppressor protein , p16INK4A , which decelerates the cell cycle by inactivating CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The p16INK4a tumor suppressor protein functions as an inhibitor of CDK 4 and CDK 6 , the D type cyclin dependent kinases that initiate the phosphorylation of the retinoblastoma tumor suppressor protein , RB . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Expression of high levels of p 16 ( INK4a ) in cells leads to the formation of a heterotrimeric complex composed of Cdk 6 , KSHV cyclin , and p 16 ( INK4a ) . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
Assays using model reporter constructs as well as endogenous target genes showed that the activity of c Myb was inhibited by cyclin D 1 plus CDK 4 or CDK 6 but stimulated by expression of the CDK inhibitors p 16 Ink4a , p 21 Cip1 , or p 27 Kip1 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
This effect of CDK 6 does not require its kinase activity and is inhibited by cyclin D 1 and p16INK4a . ^^^
Interacting proteins: Q00534 and P42771	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: Q00534 and P42771	Pubmed	SVM Score :0.0
Intriguingly , down regulation of TSC proteins was also observed by the expression of a mutant cyclin D 1 that is unable to bind to CDK4 / 6 , or by the coexpression of cyclin D 1 with either an INK 4 inhibitor or with catalytically inactive CDK 6 , indicating that cyclin D may regulate TSC 1 TSC2 independently of CDK4 / 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
K cyclin encoded by Kaposi ' s sarcoma associated herpesvirus confers resistance to the cyclin dependent kinase ( cdk ) inhibitors p16Ink4A , p21Cip1 , and p27Kip1 on the associated cdk 6 . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
The complex was modeled from CDK 6 p16INK4a 10 ray crystal structure and through molecular dynamics . ^^^
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P42771	Pubmed	SVM Score :0.0
NA