Cdc25B activity is regulated by 14-3-3

Forrest, A. and Gabrielli, B. (2001) Cdc25B activity is regulated by 14-3-3. Oncogene, 20 32: 4393-4401. doi:10.1038/sj.onc.1204574


Author Forrest, A.
Gabrielli, B.
Title Cdc25B activity is regulated by 14-3-3
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2001
Sub-type Article (original research)
DOI 10.1038/sj.onc.1204574
Volume 20
Issue 32
Start page 4393
End page 4401
Total pages 9
Place of publication London, United Kingdom
Publisher Nature
Collection year 2001
Language eng
Abstract In the G2 phase cell cycle checkpoint arrest, the cdc25-dependent activation of cyclin B/cdc2, a critical step in regulating entry into mitosis, is blocked. Studies in yeast have demonstrated that the inhibition of cdc25 function involves 14-3-3 binding to cdc25, In humans, two cdc25 isoforms have roles in G2/M progression, cdc25B and cdc25C, both bind 14-3-3, Abrogating 14-3-3 binding to cdc25C attenuates the G2 checkpoint arrest, but the contribution of 14-3-3 binding to the regulation of cdc25B function is unknown. Here we demonstrate that high level over-expression of cdc25B in G2 checkpoint arrested cells can activate cyclin B/cdc2 and overcome the checkpoint arrest. Mutation of the major 14-3-3 binding site, S323, or removal of the N-terminal regulatory domain are strong activating mutations, increasing the efficiency with which the mutant forms of cdc25B not only overcome the arrest, but also initiate aberrant mitosis, We also demonstrate that 14-3-3 binding to the S323 site on cdc25B blocks access of the substrate cyclin/cdks to the catalytic site of the enzyme, thereby directly inhibiting the activity of cdc25B, This provides direct mechanistic evidence that 14-3-3 binding to cdc25B can regulate its activity, thereby controlling progression into mitosis.
Keyword 14-3-3
Cdc25
G2 checkpoint
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
 
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Created: Tue, 14 Aug 2007, 15:04:45 EST