| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.79124323 |
| The interaction of Skp 2 with the substrate is further strengthened by the association of the Cdk binding site of Cks 1 with Cdk2 / cyclin E , to which phosphorylated p 27 is bound . . 0.79124323^^^ All proteins of this family have Cdk binding and anion binding sites , but only mammalian Cks 1 binds to Skp 2 and promotes the association of Skp 2 with p 27 phosphorylated on Thr 187 . 0.56399284^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.90426954 |
| The crystal structure of the Skp 1 Skp2 Cks 1 complex bound to a p 27 ( Kip 1 ) phosphopeptide shows that Cks 1 binds to the leucine rich repeat ( LRR ) domain and C terminal tail of Skp 2 , whereas p 27 ( Kip 1 ) binds to both Cks 1 and Skp 2 . 0.90426954^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| A CDK independent function of mammalian Cks 1 : targeting of SCF ( Skp 2 ) to the CDK inhibitor p27Kip1 . ^^^ Here we demonstrate that Cks 1 directs the ubiquitin mediated proteolysis of the CDK bound substrate p27Kip1 by the protein ubiquitin ligase ( E 3 ) SCF ( Skp 2 ) . ^^^ Cks 1 associates with the F box protein Skp 2 and is essential for recognition of the p27Kip1 substrate for ubiquitination in vivo and in vitro . ^^^ Using purified recombinant proteins , we reconstituted p27Kip1 ubiquitination activity and show that it is dependent on Cks 1 . ^^^ CKS 1 / mice are abnormally small , and cells derived from them proliferate poorly , particularly under limiting mitogen conditions , possibly due to elevated levels of p27Kip1 . . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Recently , we and others have shown that the small cell cycle regulatory protein Cks 1 plays a critical role in p 27 ubiquitination by increasing the binding affinity of Skp 2 for p 27 . ^^^ Here we report the development of a homogeneous time resolved fluorescence assay that allows the quantification of the molecular interactions between human recombinant Skp 2 , Cks 1 and a p 27 derived peptide phosphorylated on Thr ( 187 ) . ^^^ Using this assay , we have determined the dissociation constant of the Skp 2 Cks1 complex ( K ( d ) 140 + / 14 nM ) and have shown that Skp 2 binds phosphorylated p 27 peptide with high affinity only in the presence of Cks 1 ( K ( d ) 37 + / 2 nM ) . ^^^ Cks 1 does not bind directly to the p 27 phosphopeptide or to Skp 1 , which confirms its suggested role as an allosteric effector of Skp2 . . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| EB 1089 treatment repressed expression of mRNAs encoding the F box protein p 45 ( SKP 2 ) , a marker of poor head and neck cancer prognosis , and the cyclin kinase subunit CKS 1 , which is essential for targeting p 45 ( SKP 2 ) to p 27 ( KIP 1 ) . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Human CDK subunit 1 ( Cks 1 ) and S phase kinase associated protein 2 ( Skp 2 ) are components of the SCF ( Skp 2 ) complex , which acts as a ubiquitin ligase for p 27 ( Kip 1 ) . ^^^ In contrast , Cks 1 mRNA expression had no such relationship with p 27 ( Kip 1 ) , although Cks 1 mRNA was significantly elevated in adenocarcinomas . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Ubiquitination of p 27 requires the SCFSkp 2 ubiquitin ligase and Skp 2 F box binding protein Cks 1 . ^^^ The mechanisms by which Skp 2 recognizes Cks 1 to ubiquitylate p 27 remain obscure . ^^^ Here we show that Asp 331 in the carboxyl terminus of Skp 2 is required for its association with Cks 1 and ubiquitination of p 27 . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| We used as a model system the SCF ( Skp 2 ) complex that targets p 27 ( Kip 1 ) for ubiquitination and subsequent degradation ; this process requires an adapter protein , Cks 1 . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Recent work has demonstrated the role of cdc kinase subunit 1 ( Cks 1 ) in the ubiquitin proteasome dependent degradation of CDK inhibitor p27Kip1 protein as an essential cofactor for SCFSkp 2 ubiquitin ligase . ^^^ Although over expression of Cks 1 protein as well as it of Skp 2 might be associated with tumour progression via p27Kip1 protein degradation , it is unknown how the cellular level of Cks 1 is regulated . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| The deficiency of Cks 1 in TGF beta treated cells likely contributes to the stabilization of p27Kip1 and destabilization of Skp 2 , because in the absence of Cks 1 , SCFSkp 2 can not ubiquitinate p27Kip1 ; instead , self ubiquitination of Skp 2 occurs . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| METHODS : Quick frozen colorectal tumor samples from 30 patients were separated by electrophoresis on sodium dodecyl sulfate polyacrylamide gels , transferred to nitrocellulose , and probed with highly specific monoclonal antibodies directed against Cks 1 , Skp 2 , and p 27 ( Kip 1 ) . ^^^ A significant inverse relation was also observed between levels of Cks 1 and p 27 ( Kip 1 ) and overall survival . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Here we report that cell cycle inducer Cks 1 , which triggers ubiquitination and degradation of p 27 ( Kip 1 ) , associates with the unphosphorylated form of FGFR substrate 2 ( FRS 2 ) , an adaptor protein that is phosphorylated by FGFR kinases and recruits downstream signaling molecules . ^^^ FGF dependent activation of FGFR tyrosine kinases induces FRS 2 phosphorylation , causes release of Cks 1 from FRS 2 , and promotes degradation of p 27 ( Kip 1 ) in 3T3 cells . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| MATERIALS AND METHODS : The expression of Skp 2 , Cks 1 , and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin fixed , paraffin embedded tissue sections from 80 patients with colorectal carcinoma . ^^^ RESULTS : Overexpression of Skp 2 and Cks 1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Retinoic acid stabilizes p27Kip1 in EBV immortalized lymphoblastoid B cell lines through enhanced proteasome dependent degradation of the p45Skp2 and Cks 1 proteins . ^^^ Furthermore , we demonstrate that RA downregulates the expression of the p45Skp2 and Cks 1 proteins , two essential components of the SCF ( Skp 2 ) ubiquitin ligase complex that target p27Kip1 for degradation . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Ubiquitination of p 27 is primarily catalyzed by a multisubunit E 3 ubiquitin ligase , SCF ( Skp 2 ) , and requires an adapter protein Cks 1 . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Cdc kinase subunit 1 ( Cks 1 ) has been shown to involve in the regulation of cell cycle progression and p27Kip1 degradation . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| The present study was undertaken to examine the role of Cks 1 expression in breast cancer and its relation to p27Kip1 and Skp 2 expression and to tumor aggressiveness . ^^^ METHODS : The expressions of Cks 1 , Skp 2 , and p27Kip1 were examined immunohistochemically on formalin fixed , paraffin wax embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines . ^^^ RESULTS : The expression of Cks 1 was strongly associated with Skp 2 expression ( r = 0 . 477 ; P = 0 . 001 ) and inversely with p27Kip1 ( r = 0 . 726 ; P < 0 . 0001 ) . ^^^ CONCLUSION : These results suggest that Cks 1 is involved in p27Kip1 down regulation and may have an important role in the development of aggressive tumor behavior in breast cancer . . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| PURPOSE : Two SCF ( Skp 2 ) ubiquitin ligase related proteins , Skp 2 and cyclin dependent kinase subunit 1 ( Cks 1 ) , are involved in posttranscriptional degradation of p 27 ( Kip 1 ) tumor suppressor . ^^^ EXPERIMENTAL DESIGN : Clinicopathologic features and tissue microarray based immunohistochemical expression of p 27 ( Kip 1 ) , Skp 2 , Cks 1 , cyclin E , cyclin A , Ki 67 , and minichromosome maintenance protein 2 ( Mcm 2 ) were assessed in 70 primary myxofibrosarcomas and correlated with clinical outcomes . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Particularly , we did not detect the down regulation of Skp 2 and Cks 1 , two proteins involved in the nuclear ubiquitin dependent p27Kip1 removal . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Although combined overexpression of Skp 2 and Cks 1 rescues p 27 degradation in S phase , it can not override p 27 accumulation in G ( 1 ) phase and cell cycle arrest by oncostatin M . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Deregulation of p 27 is commonly observed in many human cancers secondary to enhanced ubiquitin mediated degradation , mediated and rate limited by its specific ubiquitin ligase subunits Skp 2 and Cks 1 . ^^^ Overexpression of Skp 2 and Cks 1 was observed in aggressive CRC and is responsible for down regulation of p 27 levels . ^^^ Both Skp 2 and Cks 1 were found to be independent prognostic markers for survival and provide predictive information additional to that provided by p 27 alone . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Ubiquitination of p 27 ( kip 1 ) is performed by the SCF ( skp 2 ) ubiquitin ligase comprised of the core components Roc 1 , Cul 1 and Skp 1 and the substrate recognition components Skp 2 and Cks 1 . ^^^ CD 28 costimulation mediates transcription of SKP 2 and CKS 1 , the substrate recognition components of SCFSkp 2 ubiquitin ligase that leads p27kip1 to degradation . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| CKS1B mRNA and protein expression were correlated and both were inversely correlated with p 27 ( Kip 1 ) protein levels . ^^^ Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma . ^^^ In particular , over expression of CKS1B , which maps to an amplicon at 1q21 in myeloma and regulates SCF ( Skp 2 ) mediated ubquitination and proteolysis of the cyclin dependent kinase inhibitor p27Kip1 was significantly over expressed in patients with poor survival . ^^^ RNA interference of CKS1B messenger RNA in myeloma cell lines led to reduced CKS1B mRNA and protein , an accumulation of p27Kip1 , and profound growth inhibition . ^^^ Based on these data we conclude that over expression of CKS1B , mainly due to gene amplification , imparts a poor prognosis in MM , possibly as a result of enhanced degradation of p27Kip1 . . ^^^ |
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| Interacting proteins: P61024 and P46527 |
Pubmed |
SVM Score :0.0 |
| Application of high throughput genomics on a large uniformly untreated cohort of patients has revealed that activation of 1 of the 3 cyclin D genes is a universal initiating event in this disease and that acquisition of abnormalities of chromosome 1 leads to activation of CKS1B , a regulator of p27Kip1 degradation . ^^^ |
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