| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :1.0000235 |
| 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 . 1.0000235^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.5017667 |
| 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 . 0.5017667^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| The cell cycle regulatory protein Cks 1 is required for SCF ( Skp 2 ) mediated ubiquitinylation of p 27 . ^^^ Human Cks 1 , but not other members of the family , reconstitutes ubiquitin ligation of p 27 in a completely purified system , binds to Skp 2 and greatly increases binding of T 187 phosphorylated p 27 to Skp 2 . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| Cks 1 , a subunit of cyclin dependent kinases , has now been identified as an essential cofactor in the ubiquitination of the Cdk inhibitor p 27 by the SCF ( Skp 2 ) ubiquitin ligase . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
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 ) . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
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 Q13309 |
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 ) . ^^^ These results suggest that high expression of Skp 2 and Cks 1 may be involved in the pathogenesis of NSCLCs via different mechanisms . . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| We show here that p 21 is a good substrate for an SCF ( Skp 1 Cullin1 F box protein ) ubiquitin ligase complex , which contains the F box protein Skp 2 ( S phase kinase associated protein 2 ) and the accessory protein Cks 1 ( cyclin kinase subunit 1 ) . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
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 . ^^^ Mutation of Asp 331 to Ala disrupts the interaction between Skp 2 and Cks 1 . ^^^ Our results revealed a unique requirement for a negatively charged residue in the carboxyl terminal region of Skp 2 in recognition of Cks 1 and ubiquitination of p27 . . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
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 Q13309 |
Pubmed |
SVM Score :0.0 |
| 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 Q13309 |
Pubmed |
SVM Score :0.0 |
| Human Cdk subunit 1 ( Cks 1 ) , as well as S phase kinase associated protein 2 ( Skp 2 ) , is an essential and specific factor in the p 27 proteolysis by SCF ( Skp 2 ) ubiquitin ligase . ^^^ Moreover , we established Cks 1 and / or Skp 2 transfected gastric carcinoma cell lines and assessed the relationship between Cks 1 , Skp 2 , and p 27 expression using quantitative reverse transcription PCR and Western blot analysis . ^^^ CONCLUSIONS : These findings indicate that Cks 1 , as well as Skp 2 , regulates the expression level of p 27 protein in gastric carcinomas . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
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 Q13309 |
Pubmed |
SVM Score :0.0 |
| Skp 2 and its cofactor Cks 1 are the substrate targeting subunits of the SCF ( Skp 2 Cks1 ) ( Skp1 / Cul1 / F box protein ) ubiquitin ligase complex that regulates entry into S phase by inducing the degradation of the cyclin dependent kinase inhibitors p 21 and p 27 ( ref . 1 ) . ^^^ Here we show that both Skp 2 and Cks 1 proteins are unstable in G 1 and that their degradation is mediated by the ubiquitin ligase APC / C ( Cdh 1 ) ( anaphase promoting complex / cyclosome and its activator Cdh 1 ) . ^^^ Silencing of Cdh 1 by RNA interference in G 1 cells stabilizes Skp 2 and Cks 1 , with a consequent increase in p 21 and p 27 proteolysis . ^^^ Thus , the induction of Skp 2 and Cks 1 degradation in G 1 represents a principal mechanism by which APC / C ( Cdh 1 ) prevents the unscheduled degradation of SCF ( Skp 2 Cks1 ) substrates and maintains the G 1 state . . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| The essential role of cyclin kinase subunit 1 ( Cks 1 ) in Skp 2 dependent p 27 degradation was recently discovered , but its role in human malignancies is unknown . ^^^ 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 ) . ^^^ RESULTS : A strong correlation was found between Cks 1 levels and Skp 2 expression and loss of tumor differentiation . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| By keeping the levels of Skp 2 and Cks 1 low during G ( 1 ) progression , APC / C ( Cdh 1 ) prevents unscheduled degradation of SCF ( Skp 2 ) substrates and premature entry into S phase . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| Proteasomal degradation of p 27 requires its ubiquitylation by the SCF ubiquitin ligase , with specific addressing by the F box protein Skp 2 and its co factor Cks 1 . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| Ubiquitination of p 27 requires an adapter protein , Cks 1 , to be in direct association with Skp 2 . ^^^ The exact interface between Skp 2 and Cks 1 has not been elucidated . ^^^ Here we have reported the definition of the critical functional interface between Skp 2 and Cks 1 . ^^^ We have identified eight amino acid residues in two discrete regions of Skp 2 that are engaged in Cks 1 binding . ^^^ Mutation of any of these eight residues alone or in combination results in the loss of Cks 1 association and negates Skp 2 dependent p 27 ubiquitination . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| Role of Cks 1 overexpression in oral squamous cell carcinomas : cooperation with Skp 2 in promoting p 27 degradation . ^^^ Another protein called Cks 1 is also required for p 27 ubiquitination in the SCF ( Skp 2 ) ubiquitinating machinery . ^^^ Finally , Cks 1 expression was well correlated with Skp 2 expression and poor prognosis . ^^^ To study the role of Cks 1 overexpression in p 27 down regulation , we transfected Cks 1 with or without Skp 2 into OSCC cells . ^^^ Cks 1 transfection could not induce a p 27 down regulation by itself , but both Cks 1 and Skp 2 transfection strongly induced . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| More recent evidence suggests that Skp 2 and Cks 1 , the specific recognition factors for p 27 ubiquitination , have oncogenic properties . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| The prognostic impact of the ubiquitin ligase subunits Skp 2 and Cks 1 in colorectal carcinoma . ^^^ Recently , Skp 2 and Cks 1 expression were found to be increased in some colorectal carcinomas , but their potential role as prognostic markers for survival is unknown . ^^^ The present study was undertaken to assess the prognostic value of both Skp 2 and Cks 1 in colorectal carcinoma . ^^^ 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 Q13309 |
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 . ^^^ Downregulation of p45Skp2 ) and Cks 1 occurs before the onset of growth arrest and is due to enhanced proteasome mediated proteolysis of these proteins . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| Here we use NMR spectroscopy and molecular dynamics simulations to investigate the dynamic properties of human Cks 1 and its response on assembly with components of the SCF ( Skp 2 ) ubiquitin ligation machinery . ^^^ 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 . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
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 Q13309 |
Pubmed |
SVM Score :0.0 |
| The decrease in the levels of this protein is the result of increased proteasome dependent degradation , mediated and rate limited by its specific ubiquitin ligase subunits S phase kinase protein 2 ( Skp 2 ) and cyclin dependent kinase subunit 1 ( Cks 1 ) . ^^^ Skp 2 was recently found to be overexpressed in breast cancers , but the role of Cks 1 in these cancers is unknown . ^^^ 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 ) . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| Structural basis of the Cks 1 dependent recognition of p 27 ( Kip 1 ) by the SCF ( Skp 2 ) ubiquitin ligase . ^^^ 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 . ^^^ The phosphorylated Thr 187 side chain of p 27 ( Kip 1 ) is recognized by a Cks 1 phosphate binding site , whereas the side chain of an invariant Glu 185 inserts into the interface between Skp 2 and Cks 1 , interacting with both . ^^^ 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 . . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| We provide evidence that FoxM 1 is essential for transcription of Skp 2 and Cks 1 , which are specificity subunits of the Skp 1 Cullin 1 F box ( SCF ) ubiquitin ligase complex that targets these CDKI proteins for degradation during the G ( 1 ) / S transition . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
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 Q13309 |
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 Q13309 |
Pubmed |
SVM Score :0.0 |
| Oncostatin M induces growth arrest by inhibition of Skp 2 , Cks 1 , and cyclin A expression and induced p 21 expression . ^^^ Oncostatin M inhibits expression of two components of this E 3 ligase complex ( Skp 2 and Cks 1 ) . ^^^ 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 Q13309 |
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 Q13309 |
Pubmed |
SVM Score :0.0 |
| Because levels of Skp 2 , cyclin E , and the accessory protein Cks 1 ( cyclin kinase subunit 1 ) all rise at the end of G ( 1 ) phase , it seemed possible that the neddylation of Cul 1 in SCF ( Skp 2 ) is regulated by the availability of the F box protein and / or the substrate . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ 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 . ^^^ In contrast , the substrate recognition components Skp 2 and Cks 1 are almost undetectable in resting T cells and are transcriptionally induced upon costimulation . ^^^ |
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| Interacting proteins: P61024 and Q13309 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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