Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor.

Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor. Research Abstract Details 

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Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor. Abstract Text:

Pei-Ching Chang,Mengtao Li,Pei-Ching Chang,Mengtao Li,

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 Ser(33) 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.

Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor. Publishing Authors By Initials

PC Chang,M Li,PC Chang,M Li,

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Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of virology

VOLUME: 82

Page Numbers: 278-90

Journal Abbreviation: J. Virol.

ISSN: 1098-5514

DAY: 17

MONTH: 10

YEAR: 2007

Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor. Information

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LANGUAGE: eng

NlmUniqueID: 113724

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Grant and Affiliation Information for Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor.

AFFILIATION: Center for Oral Health Research, University of Kentucky College of Dentistry, Lexington, Kentucky 40536, USA.

Country: United States

AGENCY: United States NIDCR

GRANT: DE016644-02

ACRONYM: DE

MEDLINETA: J Virol

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