title: Phosphorylation of CDC25A on SER283 in late S/G2 by CDK/cyclin complexes accelerates mitotic entry.
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.
authors: a Centre de Recherche en Cancérologie de Toulouse, INSERM UMR1037, CNRS ERL5294 , Université Toulouse III Paul Sabatier , Toulouse , France.|b Equipe labellisée LIGUE contre le Cancer , CNRS ERL5294 , Toulouse , France.
authors: Laurent
authors: L
authors: Mazzolini
authors: a Centre de Recherche en Cancérologie de Toulouse, INSERM UMR1037, CNRS ERL5294 , Université Toulouse III Paul Sabatier , Toulouse , France.
authors: Anaïs
authors: A
authors: Broban
authors: c Institut de Pharmacologie et de Biologie Structurale , Université Toulouse III Paul Sabatier Toulouse , CNRS UMR5089 , Toulouse , France.
authors: Carine
authors: C
authors: Froment
authors: c Institut de Pharmacologie et de Biologie Structurale , Université Toulouse III Paul Sabatier Toulouse , CNRS UMR5089 , Toulouse , France.
authors: Odile
authors: O
authors: Burlet-Schiltz
authors: a Centre de Recherche en Cancérologie de Toulouse, INSERM UMR1037, CNRS ERL5294 , Université Toulouse III Paul Sabatier , Toulouse , France.|b Equipe labellisée LIGUE contre le Cancer , CNRS ERL5294 , Toulouse , France.
authors: Arnaud
authors: A
authors: Besson
authors: a Centre de Recherche en Cancérologie de Toulouse, INSERM UMR1037, CNRS ERL5294 , Université Toulouse III Paul Sabatier , Toulouse , France.|b Equipe labellisée LIGUE contre le Cancer , CNRS ERL5294 , Toulouse , France.
authors: Stéphane
authors: S
authors: Manenti
authors: a Centre de Recherche en Cancérologie de Toulouse, INSERM UMR1037, CNRS ERL5294 , Université Toulouse III Paul Sabatier , Toulouse , France.|b Equipe labellisée LIGUE contre le Cancer , CNRS ERL5294 , Toulouse , France.
authors: Christine
authors: C
authors: Dozier
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D016195:G2 Phase; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D013058:Mass Spectrometry; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D055550:Protein Stability / Q000187:drug effects; D016196:S Phase; D012694:Serine / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016213:Cyclins; D012694:Serine; D018844:Cyclin-Dependent Kinases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases
keywords: CDK-cyclin; Cdc25A; G2/M transition; activating phosphorylation; cell cycle