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Chk1 Kinase Negatively Regulates Mitotic Function of Cdc25A Phosphatase Through 14-3-3 Binding

Overview
Journal Mol Cell Biol
Specialty Cell Biology
Date 2003 Oct 16
PMID 14559997
Citations 94
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Abstract

The order and fidelity of cell cycle events in mammals is intimately linked to the integrity of the Chk1 kinase-Cdc25A phosphatase pathway. Chk1 phosphorylation targets Cdc25A for destruction and, as shown here, inhibits interactions between Cdc25A and its mitotic substrate cyclin B1-Cdk1. Phosphorylation of Cdc25A on serine 178 and threonine 507 facilitates 14-3-3 binding, and Chk1 phosphorylates both residues in vitro. Mutation of T507 to alanine (T507A) enhanced the biological activity of Cdc25A. Cdc25A(T507A) was more efficient in binding to cyclin B1, activating cyclin B1-Cdk1, and promoting premature entry into mitosis. We propose that the Chk1/Cdc25A/14-3-3 pathway functions to prevent cells from entering into mitosis prior to replicating their genomes to ensure the fidelity of the cell division process.

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References
1.
Wang B, Yang H, Liu Y, Jelinek T, Zhang L, Ruoslahti E . Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display. Biochemistry. 1999; 38(38):12499-504. DOI: 10.1021/bi991353h. View

2.
Powers E, Thompson D, He W, Yem A, Bannow C, Staples D . Identification of a C-terminal cdc25 sequence required for promotion of germinal vesicle breakdown. Biochem J. 2000; 347 Pt 3:653-60. PMC: 1221000. View

3.
Heald R, McLoughlin M, McKeon F . Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. Cell. 1993; 74(3):463-74. DOI: 10.1016/0092-8674(93)80048-j. View

4.
Shimuta K, Nakajo N, Uto K, Hayano Y, Okazaki K, Sagata N . Chk1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition. EMBO J. 2002; 21(14):3694-703. PMC: 125399. DOI: 10.1093/emboj/cdf357. View

5.
Yang J, Winkler K, Yoshida M, Kornbluth S . Maintenance of G2 arrest in the Xenopus oocyte: a role for 14-3-3-mediated inhibition of Cdc25 nuclear import. EMBO J. 1999; 18(8):2174-83. PMC: 1171301. DOI: 10.1093/emboj/18.8.2174. View