title: CDC25B involvement in the centrosome duplication cycle and in microtubule nucleation.
abstract: Centrosome amplification is frequently reported in human cancers, although the molecular mechanisms that are responsible for this remain unclear. There is significant evidence to support a role for cyclin-dependent kinase (CDK)-cyclin complexes in centrosome duplication. The activities of CDK-cyclin complexes are, in turn, regulated by the CDC25 family of phosphatases in a strict spatiotemporal manner, and we have recently reported that CDC25B localizes to the centrosomes from early S phase. In the present study, we have investigated the role of centrosomally localized CDC25B in centrosome duplication. We first observed that overexpression of CDC25B under an inducible promoter in S phase results in centrosome overduplication. We found that forced expression of wild-type but not phosphatase-inactive CDC25B at the centrosomes results in centrosome amplification, aberrant microtubule organization, and abnormal accumulation of gamma-tubulin. In contrast, inhibition of CDC25B phosphatase activity inhibits the assembly of interphase microtubules and the centrosomal localization of gamma-tubulin. We propose that CDC25B is part of the pathway that controls the localization of gamma-tubulin to the centrosomes, thereby regulating centrosome duplication during S phase and the nucleation of microtubules. We speculate that abnormal expression of CDC25B in numerous human tumors might therefore have a critical role in centrosome amplification and genomic instability.
authors: Laboratoire de Biologie Cellulaire et Moléculaire du Controle de la Prolifération-Centre National de la Recherche Scientifique UMR5088, IFR109, University of Toulouse, Toulouse, France.
authors: Rose
authors: R
authors: Boutros
authors: Valérie
authors: V
authors: Lobjois
authors: Bernard
authors: B
authors: Ducommun
mesh_terms: D001859:Bone Neoplasms; D045744:Cell Line, Tumor; D018385:Centrosome / Q000502:physiology*; D005434:Flow Cytometry; D005784:Gene Amplification; D005822:Genetic Vectors; D042822:Genomic Instability; D006801:Humans; D007399:Interphase; D012516:Osteosarcoma; D010957:Plasmids; D034622:RNA Interference; D016196:S Phase; D014162:Transfection; D020687:cdc25 Phosphatases / Q000235:genetics*
chemical_list: C517008:CDC25B protein, human; D020687:cdc25 Phosphatases