| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Regulation of cyclin A Cdk 2 by SCF component Skp 1 and F box protein Skp 2 . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| The cyclin dependent kinase ( CDK ) inhibitor p27Kip1 plays a key role in growth and development of the mammary epithelium and in breast cancer . p27Kip1 levels are regulated through ubiquitin / proteasome mediated proteolysis , promoted by CDK 2 and the F box protein Skp 2 at the G1 / S transition , and independent of Skp 2 in mid G 1 . ^^^ |
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| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Finally , we show that multiprotein complex formation involving p 45 ( SKP 2 ) CUL 1 and p 19 ( SKP 1 ) is governed , in part , by periodic , S phase specific accumulation of the p 45 ( SKP 2 ) subunit and by the p 45 ( SKP 2 ) bound cyclin A CDK 2 . ^^^ The dependency of p 45 ( SKP 2 ) p 19 ( SKP 1 ) complex formation on cyclin A CDK 2 may ensure tight coordination of the activities of the cell cycle clock with those of a potential ubiquitin conjugation pathway . . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Activation of CDK 2 and binding to SKP 2 or p 27 ( KIP 1 ) were not affected by the phosphorylation of Ser 154 . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| A multiparametric analysis identified proteins associated with increased growth fraction ( Hdm 2 , p 53 , p 21 , Rb , cyclins A , B 1 , D 3 , and E , CDK 2 , CDK 6 , SKP 2 , Bcl 10 ( L ) , survivin , STAT 1 , and STAT 3 ) , and proteins associated with apoptosis ( NF kappaB , STAT 1 , and RB ) . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| VD / EB1089 significantly restricted the association of p 27 with Skp 2 as well as with cyclin dependent kinase 2 ( CDK 2 ) . ^^^ This effect is mediated at least partially through diminished p 27 association with Skp 2 and with CDK 2 . ^^^ |
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| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Because Cdk 2 mediated phosphorylation of p 27 at Thr 187 targets p 27 for Skp 2 mediated degradation , we examined the phosphorylation status of p 27 in 1 , 25 ( OH ) 2D3 treated cells . 1 , 25 ( OH ) 2D3 decreased levels of Thr 187 phosphorylated p 27 , consistent with inhibition of Thr 187 phosphorylation dependent p 27 degradation . ^^^ |
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| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Induction of ERbeta reduces growth of exponentially proliferating cells with a concomitant decrease in components of the cell cycle associated with proliferation , namely cyclin E , Cdc25A ( a key regulator of Cdk 2 ) , p 45 ( Skp 2 ) ( a key regulator of p 27 ( Kip 1 ) proteolysis ) , and an increase in the Cdk inhibitor p 27 ( Kip 1 ) . ^^^ |
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| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Kip 1 ) stabilization and G ( 1 ) arrest by 1 , 25 dihydroxyvitamin D ( 3 ) in ovarian cancer cells mediated through down regulation of cyclin E / cyclin dependent kinase 2 and Skp 1 Cullin F box protein / Skp2 ubiquitin ligase . p 27 ( Kip 1 ) ( p 27 ) is a tumor suppressor whose stability is controlled by proteasome mediated degradation , a process directed in part by cyclin dependent kinase 2 ( CDK 2 ) mediated phosphorylation of p 27 at Thr ( 187 ) and its subsequent interaction with the Skp 1 Cullin F box protein / Skp2 ( Skp 2 ) ubiquitin ligase . ^^^ It is the combined effect of 1 , 25 ( OH ) ( 2 ) D ( 3 ) on both the CDK 2 dependent phosphorylation of p 27 , and thus its affinity for Skp 2 , and Skp 2 expression that dramatically increases the stability of the p 27 protein . ^^^ Taken together , the results of this study identify p 27 as the key mediator of 1 , 25 ( OH ) ( 2 ) D ( 3 ) induced growth suppression in G ( 1 ) and show that the hormone achieves this by decreasing the activity of CDK 2 and reducing the abundance of Skp 2 , which act together to degrade p27 . . ^^^ |
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| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Regulated turnover of p 27 is due , at least partly , to its phosphorylation by Cdk 2 on threonine 187 , which generates a Skp 2 binding site . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| We previously reported that the prostacyclin mimetic , cicaprost , selectively inhibits cyclin E cyclin dependent kinase 2 ( Cdk 2 ) , and now we show that it acts by regulating the expression of Skp 2 , the F box protein that targets p 27 ( Kip 1 ) for ubiquitin mediated proteolysis . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| These data suggest that p 27 proteolysis is necessary for the activation of not only Cdk 2 but also Cdc 2 , and that Skp 2 contributes to regulation of G ( 2 ) M progression by mediating the degradation of p27 . . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Finally , increasing the amount of both cyclin E cdk 2 and skp 2 was less efficient at promoting p 27 ubiquitination than was increasing the amount of cyclin A cdk 2 alone in extracts prepared from cultures of > 93 % purified G ( 1 ) cells . ^^^ Together these lines of evidence suggest that cyclin A cdk 2 plays an ancillary noncatalytic role in the ubiquitination of p 27 by the SCF ( skp 2 ) complex . . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| To answer these questions in colorectal tumors , Skp 2 , cyclin A , cyclin B 1 , cyclin E , CDK 2 , and Ki 67 were immunohistochemically stained in 12 normal mucosa , 36 adenomas , 11 carcinomas in adenomas , 102 primary carcinomas , and 12 paired lymph node metastases ; and Skp 2 was examined by Western blot in 8 pairs of normal mucosa and carcinomas . ^^^ High Skp 2 was also significantly linked with elevated cyclin A , cyclin B 1 , cyclin E , CDK 2 ( in primary carcinomas only ) , and Ki 67 in both adenomas and primary carcinomas . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| But binding of tuberin to p 27 sequesters p 27 from Skp 2 accompanied by an up regulation of the p 27 interaction with cdk 2 . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Specific degradation of p 27 by co expressing Skp 2 or p 27 small interfering RNA caused an increase of CDK 2 activity and overrode the limited cell cycle . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| We show that core protein suppresses the expression of tumor suppressor protein p 53 and cyclin dependent kinase ( CDK ) inhibitor p 21 and enhances the activation of cyclin dependent kinase 2 ( CDK 2 ) , the phosphorylation of retinoblastoma ( Rb ) , the activation of the transcription factor E2F 1 , and the expression of E2F 1 and S phase kinase interacting protein 2 ( SKP 2 ) genes . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| This response was specific to Cdk 2 binding ; in contrast , binding of Skp 2 , a ligand unique to human Cks 1 , did not alter the dynamic behavior . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Using phosphopeptide mapping and mutagenesis studies , we found that threonine 29 within the N terminus of Cdt 1 is phosphorylated by Cdk 2 and required for interaction with Skp 2 . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| We show that Cyclin E Cdk 2 is essential for targeting the p 27 substrate to SCF ( Skp 2 ) . ^^^ Direct physical contact between Cyclin E but not Cdk 2 and p 27 is required for p 27 recruitment to SCF ( Skp 2 ) . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| The LI of skp 2 in endometrial carcinoma was significantly correlated with that of p 27 , Ki 67 , cdk 2 , cyclin A , cyclin D 1 , cyclin E , p 53 and PTEN . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| The structure and biochemical data support the proposed model that Cdk 2 cyclin A contributes to the recruitment of p 27 ( Kip 1 ) to the SCF ( Skp 2 ) Cks 1 complex . . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| The accumulation of p 27 protein in EWS Fli 1 depleted cells inhibited cdk 2 kinase activity and was related to the stability of p 27 protein , which resulted from a decrease in Skp 2 protein . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| Mutagenesis studies show that the rapid turnover of MEF in S phase is dependent on the specific phosphorylation of threonine 643 and serine 648 at the C terminus of MEF by cdk 2 and on the Skp1 / Cul1 / F box ( SCF ) E 3 ubiquitin ligase complex SCF ( Skp 2 ) , which targets MEF for ubiquitination and proteolysis . ^^^ |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13309 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|