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Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication

Oncogene volume 25, pages 2943–2949 (2006)Cite this article

Abstract

Cyclin-dependent kinase 2 (CDK2) has been proposed to function as a master regulator of centrosome duplication. Using mouse embryonic fibroblasts (MEFs) in which Cdk2 has been genetically deleted, we show here that CDK2 is not required for normal centrosome duplication, maturation and bipolar mitotic spindle formation. In contrast, Cdk2 deficiency completely abrogates aberrant centrosome duplication induced by a viral oncogene. Mechanistically, centrosome overduplication in MEFs wild-type for Cdk2 involves the formation of supernumerary immature centrosomes. These results indicate that normal and abnormal centrosome duplication have significantly different requirements for CDK2 activity and point to a role of CDK2 in licensing centrosomes for aberrant duplication. Furthermore, our findings suggest that CDK2 may be a suitable therapeutic target to inhibit centrosome-mediated chromosomal instability in tumor cells.

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Acknowledgements

We are grateful to K Munger, P Hinds, Y Chang and P Moore for sharing reagents. This work was supported by NIH/NCI Grant CA112598 (to SD).

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Authors and Affiliations

  1. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    A Duensing

  2. Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    A Duensing, Y Liu, M Tseng & S Duensing

  3. Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain

    M Malumbres & M Barbacid

  4. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    S Duensing

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  1. A Duensing
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Correspondence to S Duensing.

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Duensing, A., Liu, Y., Tseng, M. et al. Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication. Oncogene 25, 2943–2949 (2006). https://doi.org/10.1038/sj.onc.1209310

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