| Interacting proteins: P30304 and Q9Y297 |
Pubmed |
SVM Score :0.54011631 |
| Here we report that beta TrCP is the F box protein that targets phosphorylated Cdc25A for degradation by the Skp1 / Cul1 / F box protein complex . 0.54011631^^^ |
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| Interacting proteins: P30304 and Q9Y297 |
Pubmed |
SVM Score :0.0 |
| Depletion of beta TRCP stabilizes Cdc25A , leading to hyperactive Cdk 2 activity . ^^^ However , recognition of Cdc25A by beta TRCP occurs via a noncanonical phosphodegron in Cdc25A containing phosphoserine 79 and phosphoserine 82 , sites that are not targeted by Chk 1 . ^^^ |
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| Interacting proteins: P30304 and Q9Y297 |
Pubmed |
SVM Score :0.0 |
| Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP dependent degradation . ^^^ We have recently demonstrated that regulation of Cdc25A protein abundance during S phase and in response to DNA damage is mediated by SCF ( betaTrCP ) activity . ^^^ Based on sequence homology of known betaTrCP substrates , we found that Cdc25A contains a conserved motif ( DSG ) , phosphorylation of which is required for interaction with betaTrCP . 1 Here , we show that phosphorylation at Ser 82 within the DSG motif anchors Cdc25A to betaTrCP and that Chk 1 dependent phosphorylation at Ser 76 affects this interaction as well as betaTrCP dependent degradation . ^^^ We propose that a hierarchical order of phosphorylation events commits Cdc25A to betaTrCP dependent degradation . ^^^ According to our model , phosphorylation at Ser 76 is a `` priming ' ' step required for Ser 82 phosphorylation , which in turn allows recruitment of Cdc25A by betaTrCP and subsequent betaTrCP dependent degradation . . ^^^ |
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| Interacting proteins: P30304 and Q9Y297 |
Pubmed |
SVM Score :0.0 |
| Thus , loss of beta TRCP 1 may promote both growth and cell motility of lung cancer cells , possibly through regulation of CDC25A and the MMP 11 level . . ^^^ |
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| Interacting proteins: P30304 and Q9Y297 |
Pubmed |
SVM Score :0.0 |
| Transforming growth factor beta facilitates beta TrCP mediated degradation of Cdc25A in a Smad 3 dependent manner . ^^^ Two ubiquitin ligases , the Skp 1 cullin beta TrCP ( SCFbeta TrCP ) complex and the anaphase promoting complex ( APCCdh 1 ) , are involved in Cdc25A degradation . ^^^ Here we demonstrate that the transforming growth factor beta ( TGF beta ) Smad 3 pathway promotes SCF ( beta TrCP ) mediated Cdc25A ubiquitination . ^^^ TGF beta induced ubiquitination is associated with Cdc25A phosphorylation at the beta TrCP docking site ( DS82G motif ) and physical association of Cdc25A with Smad 3 and beta TrCP . ^^^ Smad 3 siRNA inhibits beta TrCP Cdc25A interaction and Cdc25A degradation in response to TGF beta . beta TrCP 2 siRNA also inhibits Smad 3 induced Cdc25A degradation . ^^^ |
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| Interacting proteins: P30304 and Q9Y297 |
Pubmed |
SVM Score :0.0 |
| Beta TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases . ^^^ Beta TrCP binds to the DSG motif of human Cdc25A in a manner dependent on Chk 1 and other unknown kinases . ^^^ Here , we report that both Xenopus Cdc25A and human Cdc25A have a previously undescribed nonphosphorylated DDG motif ( DDGPhiXD ) for recognition by beta TrCP . ^^^ When analyzed by using Xenopus eggs , the binding of beta TrCP to the DDG motif is essential for the Chk 1 induced ubiquitination and degradation of Xenopus Cdc25A and also plays a role in the degradation of human Cdc25A . ^^^ We provide strong evidence that , in both Cdc25A and Cdc25B , the binding ( efficiency ) of beta TrCP to the DDG motif is regulated by nearby residues , while ubiquitination is regulated by other events in addition to the beta TrCP binding . ^^^ |
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