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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.
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https://hal.archives-ouvertes.fr/hal-00317336
Contributor : Bernard Ducommun <>
Submitted on : Wednesday, September 3, 2008 - 2:43:25 PM
Last modification on : Wednesday, January 20, 2021 - 3:22:04 PM

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Rose Boutros, Valérie Lobjois, Bernard Ducommun. CDC25B involvement in the centrosome duplication cycle and in microtubule nucleation.. Cancer Research, American Association for Cancer Research, 2007, 67 (24), pp.11557-64. ⟨10.1158/0008-5472.CAN-07-2415⟩. ⟨hal-00317336⟩

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