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14-3-3 Proteins Act as Negative Regulators of the Mitotic Inducer Cdc25 in Xenopus Egg Extracts

Kumagai, Akiko and Yakowec, Peter S. and Dunphy, William G. (1998) 14-3-3 Proteins Act as Negative Regulators of the Mitotic Inducer Cdc25 in Xenopus Egg Extracts. Molecular Biology of the Cell, 9 (2). pp. 345-354. ISSN 1059-1524. http://resolver.caltech.edu/CaltechAUTHORS:KUMmbc98

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Abstract

Cdc25, the dual-specificity phosphatase that dephosphorylates the Cdc2-cyclin B complex at mitosis, is highly regulated during the cell cycle. In Xenopus egg extracts, Cdc25 is associated with two isoforms of the 14-3-3 protein. Cdc25 is complexed primarily with 14-3-3epsilon and to a lesser extent with 14-3-3zeta . The association of these 14-3-3 proteins with Cdc25 varies dramatically during the cell cycle: binding is high during interphase but virtually absent at mitosis. Interaction with 14-3-3 is mediated by phosphorylation of Xenopus Cdc25 at Ser-287, which resides in a consensus 14-3-3 binding site. Recombinant Cdc25 with a point mutation at this residue (Cdc25-S287A) is incapable of binding to 14-3-3. Addition of the Cdc25-S287A mutant to Xenopus egg extracts accelerates mitosis and overrides checkpoint-mediated arrests of mitotic entry due to the presence of unreplicated and damaged DNA. These findings indicate that 14-3-3 proteins act as negative regulators of Cdc25 in controlling the G2-M transition.


Item Type:Article
Additional Information:Copyright © 1998 by The American Society for Cell Biology. Submitted September 29, 1997; Accepted November 19, 1997. Monitoring Editor: Tim Hunt. We thank the other members of our laboratory for comments on the manuscript. This work was supported in part by a grant from the NIH (GM43974). W.G.D. is an investigator of the Howard Hughes Medical Institute.
Record Number:CaltechAUTHORS:KUMmbc98
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:KUMmbc98
Alternative URL:http://www.molbiolcell.org/cgi/content/abstract/9/2/345
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ID Code:7618
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Deposited On:14 Mar 2007
Last Modified:26 Dec 2012 09:33

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