Mitotic phosphorylation of Cdc25B Ser(321) disrupts 14-3-3 binding to the high affinity Ser(323) site

Astuti, P, Boutros, R, Ducommun, B and Gabrielli, B (2010) Mitotic phosphorylation of Cdc25B Ser(321) disrupts 14-3-3 binding to the high affinity Ser(323) site. Journal of Biological Chemistry, 285 45: 34364-34370. doi:10.1074/jbc.M110.138412

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Author Astuti, P
Boutros, R
Ducommun, B
Gabrielli, B
Title Mitotic phosphorylation of Cdc25B Ser(321) disrupts 14-3-3 binding to the high affinity Ser(323) site
Formatted title
Mitotic phosphorylation of Cdc25B Ser321 disrupts 14-3-3 binding to the high affinity Ser323 site
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2010-11
Sub-type Article (original research)
DOI 10.1074/jbc.M110.138412
Open Access Status File (Publisher version)
Volume 285
Issue 45
Start page 34364
End page 34370
Total pages 7
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2011
Language eng
Formatted abstract
Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3 binding sites on Cdc25B, with Ser323 being the highest affinity binding and is highly homologous to
the Ser216 14-3-3 binding site on Cdc25C. Loss of 14-3-3 binding to Ser323 increases cyclin/Cdk substrate access to the catalytic site, thereby increasing its activity. It also affects the localization of Cdc25B. Thus, phosphorylation and 14-3-3 binding to this site is essential for down-regulating Cdc25B activity, blocking its mitosis promoting function. The question of how this inhibitory signal is relieved to allow Cdc25B activation and entry into mitosis is yet to be resolved. Here,weshow that Ser323 phosphorylation is maintained into mitosis, but phosphorylation of Ser321 disrupts 14-3-3 binding to Ser323, mimicking the effect of inhibiting Ser323 phosphorylation on both Cdc25B activity and localization. The unphosphorylated Ser321 appears to have a role in stabilizing 14-3-3 binding to Ser323, and loss of the Ser hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding.Aconsequence of loss of 14-3-3 binding is dephosphorylation of Ser323. Ser321 is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser321 acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to Ser323 and enhancing the dephosphorylationof Ser323 to block 14-3-3 binding to this site.
© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Keyword Cell cycle
CDK (Cyclin-dependent Kinase)
Dual specificity phosphoprotein phosphatase
Site-directed mutagenesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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Created: Sun, 28 Nov 2010, 00:04:22 EST