Phosphorylation of CDC25C at S263 controls its intracellular localisation.

Charlotte Esmenjaud-Mailhat (1) , Valérie Lobjois (1) , Carine Froment (2) , Roy M Golsteyn (3, 4) , Bernard Monsarrat (2) , Bernard Ducommun (1)

1 LBCMCP - Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération
2 IPBS - Institut de pharmacologie et de biologie structurale
3 Institut de Recherches Servier
4 Division Recherche et Cancérologie

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.

Domaines: Biologie cellulaire

Charlotte Esmenjaud-Mailhat, Valérie Lobjois, Carine Froment, Roy M Golsteyn, Bernard Monsarrat, et al.. Phosphorylation of CDC25C at S263 controls its intracellular localisation.. FEBS Letters, 2007, 581 (21), pp.3979-85. ⟨10.1016/j.febslet.2007.07.024⟩. ⟨hal-00317342⟩