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Loss of p53 and centrosome hyperamplification

Oncogene volume 21, pages 6234–6240 (2002)Cite this article

Abstract

Loss or mutational inactivation of p53 has been shown to lead to abnormal amplification of centrosomes through deregulation of the centrosome duplication cycle and failure to undergo cytokinesis. In mouse cells, most cases of centrosome hyperamplification are attributed to deregulation of centrosome duplication. The presence of excess copies of centrosomes increases the frequency of mitotic defects, leading to unbalanced chromosome transmission to daughter cells. p53 controls centrosome duplication via transactivation-dependent and transactivation-independent mechanisms. In its transactivation-dependent control, p21Waf1/Cip1 acts as a major effector, likely guarding against untimely activation of CDK2/cyclin E kinase, hence ensuring the coordinated initiation of centrosome and DNA duplication. p53 appears to exert its transactivation-independent control through direct physical binding to the centrosomes.

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Acknowledgements

We thank the members of the Fukasawa laboratory for experimental contribution and helpful discussion. This work was supported in part by National Institute of Health grant CA90522.

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  1. Department of Cell Biology, University of Cincinnati College of Medicine PO Box 670521, Cincinnati, 45267-0521, Ohio, OH, USA

    Pheruza Tarapore & Kenji Fukasawa

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  1. Pheruza Tarapore
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  2. Kenji Fukasawa
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Correspondence to Kenji Fukasawa.

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Tarapore, P., Fukasawa, K. Loss of p53 and centrosome hyperamplification. Oncogene 21, 6234–6240 (2002). https://doi.org/10.1038/sj.onc.1205707

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