Phosphorylation of CDC25C at S263 controls its intracellular localisation.
CDC25C phosphatase is a key actor in cell cycle progression that controls the activation of CDK1-cyclin B at mitosis. Its activity is known to be highly regulated by a number of signalling pathway-activated kinases resulting in its phosphorylation on multiple residues. In this study, we have purified CDC25C from cells and have used a proteomic approach to identify new regulatory phosphorylations. Here, we report the identification by mass spectrometry of a peptide monophosphorylated on serine 263. We demonstrate by cell imaging that mutation of S263 to alanine leads to a nuclear accumulation of CDC25C that is further reinforced by leptomycin-B. We propose that phosphorylation at S263 is part of the regulatory mechanism that modulates nuclear import of CDC25C, thus preventing cytoplasm to nucleus shuttling.
LBCMCP-CNRS, IFR109 Institut d'Exploration Fonctionnelle des Génomes, University of Toulouse, 118 Route de Narbonne, 31062 Toulouse, France.
Charlotte
C
Esmenjaud-Mailhat
Valérie
V
Lobjois
Carine
C
Froment
Roy M
RM
Golsteyn
Bernard
B
Monsarrat
Bernard
B
Ducommun
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D019943:Amino Acid Substitution; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D020125:Mutation, Missense; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D040901:Proteomics; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
D000935:Antifungal Agents; D018797:Cell Cycle Proteins; D019926:Cyclin B; D005231:Fatty Acids, Unsaturated; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; C038753:leptomycin B