Differential phosphorylation of Cdc25C phosphatase in mitosis.
Cdc25 dual-specificity phosphatases coordinate entry into mitosis through activating dephosphorylation of the Mitosis-Promoting Factor, Cdk1-cyclin B1. Activation of Cdc25C at the G2/M transition, involves its dissociation from 14-3-3, together with its hyperphosphorylation on several sites within its regulatory N-terminal domain, mediated by cyclin-dependent kinases and Plk1. Growing evidence suggests that phosphorylation intermediates are likely to precede complete hyperphosphorylation of Cdc25C. To address whether such variants occur in mitotic cells, we raised antibodies directed against different mitotic phosphorylation sites of human Cdc25C, and characterized the phosphorylated species detectable in HeLa cells. In the present study, we provide first-time evidence for the existence of multiple species of Cdc25C in mitotic cell extracts, including full-length and splice variants with different phosphorylation patterns, thereby revealing an intricate network of Cdc25C phosphatases, likely to have distinct biological functions.
Bonnet
Jérôme
J
Université de Montpellier, CRBM-CNRS-UMR 5237, Interactions & Molecular Mechanisms regulating Cell Cycle Progression, 1919 Route de Mende, IFR 122, 34293 Montpellier, France. jerome.bonnet@crbm.cnrs.fr
Mayonove
Pauline
P
Morris
May C
MC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D045163:Antibodies, Phospho-Specific / Q000276:immunology; D002457:Cell Extracts / Q000737:chemistry; D004586:Electrophoresis; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008938:Mitosis; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D020687:cdc25 Phosphatases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D045163:Antibodies, Phospho-Specific; D002457:Cell Extracts; D010750:Phosphoproteins; D020687:cdc25 Phosphatases