Phosphorylation of Human CDC25B Phosphatase by CDK1-Cyclin A Triggers Its Proteasome-dependent Degradation*
- From the Institut de Pharmacologie et de Biologie Structurale du CNRS, Université Paul Sabatier, 205 route de Narbonne, 31077 Toulouse cedex, France
Abstract
In eukaryotes the activity of CDK1 (CDC2), a cyclin-dependent kinase that initiates the structural changes that culminate in the segregation of chromosomes at mitosis, is regulated by the synergistic and opposing activities of a cascade of kinases and phosphatases. Dephosphorylation of threonine 14 and tyrosine 15 of CDK1 by the CDC25 phosphatases is a key step in the activation of the CDK1-cyclin B protein kinase. Little is currently known about the role and the regulation of CDC25B. Here we reportin vitro and in vivo data that indicate that CDC25B is degraded by the proteasome. This degradation is dependent upon phosphorylation by the CDK1-cyclin A complex but not by CDK1-cyclin B. These results indicate that CDK1-cyclin A phosphorylation targets CDC25B for degradation and that this might be an important component of cell cycle regulation at the G2/M transition.
Footnotes
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↵* This work was supported by grants from the CNRS, l’Université Paul Sabatier, l’Association pour la Recherche sur le Cancer, and la Ligue contre le Cancer Comité de la Haute-Garonne.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.
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↵‡ To whom correspondence should be addressed. Tel.: 33-5-61-17-59-31; Fax: 33-5-61-17-59-05; E-mail:ducommun{at}ipbs.fr.
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↵1 The abbreviations used are: LLnL,N-acetyl-Leu-Leu-norleucinal; FSBA,p-fluorosulfonylbenzoyl adenosine; LLM,N-acetyl-Leu-Leu-methioninal; MG132,Z-Leu-Leu-Leu-CHO; E64D, (2S,3S)-trans-epoxysuccimyl-l-leucylamido-3-methyl-butane ethyl ester; PAGE, polyacrylamide gel electrophoresis.
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- Received October 10, 1997.
- Revision received October 29, 1997.
