Mitotic and G 2 Checkpoint Control: Regulation of 14-3-3 Protein Binding by Phosphorylation of Cdc25C on Serine-216
10.1126/science.277.5331.1501
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

Human Cdc25C is a dual-specificity protein phosphatase that controls entry into mitosis by dephosphorylating the protein kinase Cdc2. Throughout interphase, but not in mitosis, Cdc25C was phosphorylated on serine-216 and bound to members of the highly conserved and ubiquitously expressed family of 14-3-3 proteins. A mutation preventing phosphorylation of serine-216 abrogated 14-3-3 binding. Conditional overexpression of this mutant perturbed mitotic timing and allowed cells to escape the G 2 checkpoint arrest induced by either unreplicated DNA or radiation-induced damage. Chk1, a fission yeast kinase involved in the DNA damage checkpoint response, phosphorylated Cdc25C in vitro on serine-216. These results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify Cdc25C as a potential target of checkpoint control in human cells.

Bibliography

Peng, C.-Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S., & Piwnica-Worms, H. (1997). Mitotic and G 2 Checkpoint Control: Regulation of 14-3-3 Protein Binding by Phosphorylation of Cdc25C on Serine-216. Science, 277(5331), 1501–1505.

Authors 6
  1. Cheng-Yuan Peng (first)
  2. Paul R. Graves (additional)
  3. Richard S. Thoma (additional)
  4. Zhiqi Wu (additional)
  5. Andrey S. Shaw (additional)
  6. Helen Piwnica-Worms (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:37 a.m.)
Deposited 1 year, 7 months ago (Jan. 12, 2024, 10:51 p.m.)
Indexed 2 days, 1 hour ago (Aug. 30, 2025, 12:37 p.m.)
Issued 27 years, 11 months ago (Sept. 5, 1997)
Published 27 years, 11 months ago (Sept. 5, 1997)
Published Print 27 years, 11 months ago (Sept. 5, 1997)
Funders 0

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@article{Peng_1997, title={Mitotic and G 2 Checkpoint Control: Regulation of 14-3-3 Protein Binding by Phosphorylation of Cdc25C on Serine-216}, volume={277}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.277.5331.1501}, DOI={10.1126/science.277.5331.1501}, number={5331}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Peng, Cheng-Yuan and Graves, Paul R. and Thoma, Richard S. and Wu, Zhiqi and Shaw, Andrey S. and Piwnica-Worms, Helen}, year={1997}, month=sep, pages={1501–1505} }