CDC25B Involvement in the Centrosome Duplication Cycle and in Microtubule Nucleation

• Published in: Cancer research (Chicago, Ill.) Vol. 67; no. 24; pp. 11557 - 11564
• Main Authors: BOUTROS, Rose, LOBJOIS, Valérie, DUCOMMUN, Bernard
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-12-2007
• Subjects: Antineoplastic agents; Biological and medical sciences; Bone Neoplasms; cdc25 Phosphatases; cdc25 Phosphatases - genetics; Cell Line, Tumor; Cellular Biology; Centrosome; Centrosome - physiology; Flow Cytometry; Gene Amplification; Genetic Vectors; Genomic Instability; Humans; Interphase; Life Sciences; Medical sciences; Osteosarcoma; Pharmacology. Drug treatments; Plasmids; RNA Interference; S Phase; Transfection; Tumors; Chromosomal aberration; Abnormal chromosome; Cytoskeleton; Microtubule; Chromosome duplication; Centrosome; Cycle
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-07-2415

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.