1. ¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2. ²Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
3. ³Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
4. ⁴Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence: S Duensing, Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Research Pavilion Suite 1.8, 5117 Centre Avenue, Pittsburgh, PA 15213, USA. E-mail: duensing@pitt.edu

Received 16 June 2005; Revised 24 October 2005; Accepted 9 November 2005; Published online 9 January 2006.

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.