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Cell Cycle. 2016 Oct 17;15(20):2742-52. doi: 10.1080/15384101.2016.1220455. Epub 2016 Aug 11.

Phosphorylation of CDC25A on SER283 in late S/G2 by CDK/cyclin complexes accelerates mitotic entry.

Author information

1
a Centre de Recherche en Cancérologie de Toulouse, INSERM UMR1037, CNRS ERL5294 , Université Toulouse III Paul Sabatier , Toulouse , France.
2
b Equipe labellisée LIGUE contre le Cancer , CNRS ERL5294 , Toulouse , France.
3
c Institut de Pharmacologie et de Biologie Structurale , Université Toulouse III Paul Sabatier Toulouse , CNRS UMR5089 , Toulouse , France.

Abstract

The Cdc25A phosphatase is an essential activator of CDK-cyclin complexes at all steps of the eukaryotic cell cycle. The activity of Cdc25A is itself regulated in part by positive and negative feedback regulatory loops performed by its CDK-cyclin substrates that occur in G1 as well as during the G1/S and G2/M transitions. However, the regulation of Cdc25A during G2 phase progression before mitotic entry has not been intensively characterized. Here, we identify by mass spectrometry analysis a new phosphorylation event of Cdc25A on Serine283. Phospho-specific antibodies revealed that the phosphorylation of this residue appears in late S/G2 phase of an unperturbed cell cycle and is performed by CDK-cyclin complexes. Overexpression studies of wild-type and non-phosphorylatable mutant forms of Cdc25A indicated that Ser283 phosphorylation increases the G2/M-promoting activity of the phosphatase without impacting its stability or subcellular localization. Our results therefore identify a new positive regulatory loop between Cdc25A and its CDK-cyclin substrates which contributes to accelerate entry into mitosis through the regulation of Cdc25A activity in G2.

KEYWORDS:

CDK-cyclin; Cdc25A; G2/M transition; activating phosphorylation; cell cycle

PMID:
27580187
PMCID:
PMC5053558
DOI:
10.1080/15384101.2016.1220455
[Indexed for MEDLINE]
Free PMC Article

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