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CDC25B Involvement in the Centrosome Duplication Cycle and in Microtubule Nucleation

¹ Laboratoire de Biologie Cellulaire et Moléculaire du Controle de la Prolifération–Centre National de la Recherche Scientifique UMR5088, IFR109, University of Toulouse, and ² CHU Purpan, Toulouse, France

Requests for reprints: Bernard Ducommun, UM5088, Laboratoire de Biologie Cellulaire et Moléculaire du Controle de la Prolifération–Centre National de la Recherche Scientifique, 118 rte de Narbonne-BAT 4R3B1, Toulouse, France 31062. Phone: 33-5-61-55-62-10; Fax: 33-5-61-55-81-09; E-mail: ducommun{at}cict.fr.

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 -tubulin. In contrast, inhibition of CDC25B phosphatase activity inhibits the assembly of interphase microtubules and the centrosomal localization of -tubulin. We propose that CDC25B is part of the pathway that controls the localization of -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. [Cancer Res 2007;67(24):11557–64]

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