Patra, Debabrata and Wang, Sophie X. and Kumagai, Akiko and Dunphy, William G. (1999) The Xenopus Suc1/Cks Protein Promotes the Phosphorylation of G2/M Regulators. Journal of Biological Chemistry, 274 (52). pp. 36839-36842. ISSN 0021-9258. https://resolver.caltech.edu/CaltechAUTHORS:PATjbc99
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Abstract
The entry into mitosis is controlled by Cdc2/cyclin B, also known as maturation or M-phase promoting factor (MPF). In Xenopus egg extracts, the inhibitory phosphorylations of Cdc2 on Tyr-15 and Thr-14 are controlled by the phosphatase Cdc25 and the kinases Myt1 and Wee1. At mitosis, Cdc25 is activated and Myt1 and Wee1 are inactivated through phosphorylation by multiple kinases, including Cdc2 itself. The Cdc2-associated Suc1/Cks1 protein (p9) is also essential for entry of egg extracts into mitosis, but the molecular basis of this requirement has been unknown. We find that p9 strongly stimulates the regulatory phosphorylations of Cdc25, Myt1, and Wee1 that are carried out by the Cdc2/cyclin B complex. Overexpression of the prolyl isomerase Pin1, which binds to the hyperphosphorylated forms of Cdc25, Myt1, and Wee1 found at M-phase, is known to block the initiation of mitosis in egg extracts. We have observed that Pin1 specifically antagonizes the stimulatory effect of p9 on phosphorylation of Cdc25 by Cdc2/cyclin B. This observation could explain why overexpression of Pin1 inhibits mitotic initiation. These findings suggest that p9 promotes the entry into mitosis by facilitating phosphorylation of the key upstream regulators of Cdc2.
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| Additional Information: | © 1999 the American Society for Biochemistry and Molecular Biology. We thank Dr. Tony Hunter (The Salk Institute, La Jolla, CA) for the plasmid encoding wild-type human His6-Pin1 and Dr. Kun Ping Lu (Beth Israel Deaconess Medical Center, Boston, MA) for the mutant Pin1-H59A protein. We are grateful to the members of the Dunphy laboratory for comments on the manuscript. This work was supported in part by Fellowships from the American Cancer Society (California Division, Inc.) (to D.P.) and the Damon Runyon-Walter Winchell Cancer Research Fund (to S.X.W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. [W.G.D.] [i]s an investigator of the Howard Hughes Medical Institute. | ||||||||
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| Issue or Number: | 52 | ||||||||
| Record Number: | CaltechAUTHORS:PATjbc99 | ||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:PATjbc99 | ||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||
| ID Code: | 12145 | ||||||||
| Collection: | CaltechAUTHORS | ||||||||
| Deposited By: | Archive Administrator | ||||||||
| Deposited On: | 25 Oct 2008 00:05 | ||||||||
| Last Modified: | 09 Mar 2020 13:18 |
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