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Journal of Virology, January 2008, p. 278-290, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01552-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus K-Cyclin Interacts with Cdk9 and Stimulates Cdk9-Mediated Phosphorylation of p53 Tumor Suppressor{triangledown}

Pei-Ching Chang and Mengtao Li*

Center for Oral Health Research, University of Kentucky College of Dentistry, Lexington, Kentucky 40536

Received 17 July 2007/ Accepted 9 October 2007

K-cyclin, encoded by Kaposi's sarcoma-associated herpesvirus, has previously been demonstrated to activate cyclin-dependent kinase 6 (Cdk6) to induce the phosphorylation of various cell cycle regulators. In this study, we identified Cdk9 as a new K-cyclin-associated Cdk and showed that K-cyclin interacted with Cdk9 through its basic domain. We hypothesized that K-cyclin served as a regulatory subunit for the activity of Cdk9. Recent reports show that Cdk9 phosphorylates tumor suppressor p53, and we found that the K-cyclin/Cdk9 interaction greatly enhanced the kinase activity of Cdk9 toward p53. The phosphorylation site(s) of K-cyclin/Cdk9 kinase complexes was mapped in the transactivation domain of p53. We showed that the ectopic expression of K-cyclin led to a sustained increase of p53 phosphorylation on Ser33 in vivo, and the phosphorylation could be inhibited by a dominant negative Cdk9 mutant, dn-Cdk9. Using p53-positive U2OS and p53-null SaOS2 cells, we demonstrated that K-cyclin-induced growth arrest was associated with the presence of p53. In addition, K-cyclin-induced p53-dependent growth arrest was rescued by the dn-Cdk9- or Cdk9-specific short hairpin RNA in SaOS2 cells. Together, our findings for the first time demonstrated the interaction of K-cyclin and Cdk9 and revealed a new molecular link between K-cyclin and p53.

* Corresponding author. Mailing address: 800 Rose Street, Lexington, KY 40536-0297. Phone: (859) 323-0011. Fax: (859) 257-6566. E-mail: mli4{at}email.uky.edu

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, January 2008, p. 278-290, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01552-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kapasi, A. J., Clark, C. L., Tran, K., Spector, D. H. (2009). Recruitment of cdk9 to the Immediate-Early Viral Transcriptosomes during Human Cytomegalovirus Infection Requires Efficient Binding to Cyclin T1, a Threshold Level of IE2 86, and Active Transcription. J. Virol. 83: 5904-5917 [Abstract] [Full Text]  
  • Durand, L. O., Roizman, B. (2008). Role of cdk9 in the Optimization of Expression of the Genes Regulated by ICP22 of Herpes Simplex Virus 1. J. Virol. 82: 10591-10599 [Abstract] [Full Text]  


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