title: Kizuna is a novel mitotic substrate for CDC25B phosphatase.
abstract: CDC25 dual-specificity phosphatases play a central role in cell cycle control through the activation of Cyclin-Dependent Kinases (CDKs). Expression during mitosis of a stabilized CDC25B mutant (CDC25B-DDA), which cannot interact with the F-box protein βTrCP for proteasome-dependent degradation, causes mitotic defects and chromosome segregation errors in mammalian cells. We found, using the same CDC25B mutant, that stabilization and failure to degrade CDC25B during mitosis lead to the appearance of multipolar spindle cells resulting from a fragmentation of pericentriolar material (PCM) and abolish mitotic Plk1-dependent phosphorylation of Kizuna (Kiz), which is essential for the function of Kiz in maintaining spindle pole integrity. Thus, in mitosis Kiz is a new substrate of CDC25B whose dephosphorylation following CDC25B stabilization leads to the formation of multipolar spindles. Furthermore, endogenous Kiz and CDC25B interact only in mitosis, suggesting that Kiz phosphorylation depends on a balance between CDC25B and Plk1 activities. Our data identify a novel mitotic substrate of CDC25B phosphatase that plays a key role in mitosis control.
authors.affiliation: a Centre de Recherche de Biochimie Macromoléculaire (CRBM); ; Montpellier , France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Thomas
authors.forename: Marion
authors.initials: M
authors.lastname: Peter
authors.forename: Francisca
authors.initials: F
authors.lastname: Mechali
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Blanchard
authors.forename: Olivier
authors.initials: O
authors.lastname: Coux
authors.forename: Véronique
authors.initials: V
authors.lastname: Baldin
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D020687:cdc25 Phosphatases; D000097869:Polo-Like Kinase 1; C000588439:KIZ protein, human
keywords: CDC25B; DMSO, dimethyl-sulfoxyde; DSP, Dithiobis [succinimidyl propionate]; Kiz, Kizuna protein; Kizuna; PCM, pericentriolar material; centrosome; mitosis