Abstract
Degradation of mitotic cyclins on exit from M phase occurs by ubiquitin-mediated proteolysis. The ubiquitination of mitotic cyclins is regulated by the anaphase-promoting complex (APC) or cyclosome. Xe-p9, the Xenopus homolog of the Suc1/Cks protein, is required for some step in mitotic cyclin destruction inXenopus egg extracts. Specifically, if p9 is removed from interphase egg extracts, these p9-depleted extracts are unable to carry out the proteolysis of cyclin B after entry into mitosis and thus remain arrested in M phase. To explore the molecular basis of this defect, we depleted p9 from extracts that had already entered M phase and thus contained an active APC. We found that ubiquitin-mediated proteolysis of cyclin B was not compromised under these circumstances, suggesting that p9 is not directly required for ubiquitination or proteolysis. Further analysis of extracts from which p9 had been removed during interphase showed that, at the beginning of mitosis, these extracts are unable to carry out the hyperphosphorylation of the Cdc27 component of the APC, which coincides with the initial activation of the APC. p9 can be found in a complex with a small fraction of the Cdc27 protein during M phase but not interphase. The phosphorylation of the Cdc27 protein (either associated with the APC or in an isolated, bacterially expressed form) by recombinant Cdc2/cyclin B is strongly enhanced by p9. Our results indicate that p9 directly regulates the phosphorylation of the APC by Cdc2/cyclin B. These studies indicate that the Suc1/Cks protein modulates substrate recognition by a cyclin-dependent kinase.
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Dates
Type | When |
---|---|
Created | 17 years, 6 months ago (Feb. 20, 2008, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 10:20 p.m.) |
Indexed | 1 month, 1 week ago (July 23, 2025, 8:27 a.m.) |
Issued | 27 years ago (Aug. 15, 1998) |
Published | 27 years ago (Aug. 15, 1998) |
Published Online | 27 years ago (Aug. 15, 1998) |
Published Print | 27 years ago (Aug. 15, 1998) |
@article{Patra_1998, title={Xe-p9, a Xenopus Suc1/Cks protein, is essential for the Cdc2-dependent phosphorylation of the anaphase- promoting complex at mitosis}, volume={12}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.12.16.2549}, DOI={10.1101/gad.12.16.2549}, number={16}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Patra, Debabrata and Dunphy, William G.}, year={1998}, month=aug, pages={2549–2559} }