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

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


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.

MeSH terms

  • Amino Acid Sequence
  • Cell Line, Tumor
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclins / metabolism*
  • G2 Phase*
  • Humans
  • Intracellular Space / metabolism
  • Mass Spectrometry
  • Mitosis*
  • Mutation / genetics
  • Phosphorylation
  • Protein Stability / drug effects
  • S Phase*
  • Serine / metabolism*
  • cdc25 Phosphatases / chemistry
  • cdc25 Phosphatases / metabolism*


  • Cyclins
  • Serine
  • Cyclin-Dependent Kinases
  • CDC25A protein, human
  • cdc25 Phosphatases