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. PMCID PMC25261. http://resolver.caltech.edu/CaltechAUTHORS:KUMmbc98
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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.
|Additional Information:||Copyright © 1998 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0). 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.|
|PubMed Central ID:||PMC25261|
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|Deposited On:||14 Mar 2007|
|Last Modified:||22 Sep 2015 19:39|
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