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Journal of Virology, August 2001, p. 7572-7582, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7572-7582.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Inhibition of p53 Tumor Suppressor by Viral Interferon Regulatory Factor

Hiroyuki Nakamura, Mengtao Li,dagger Jodi Zarycki, and Jae U. Jung*

Department of Microbiology and Molecular Genetics, Tumor Virology Division, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772

Received 19 January 2001/Accepted 8 May 2001

The irreversible cell cycle arrest and apoptosis induced by p53 are part of the host surveillance mechanisms for viral infection and tumor induction. Kaposi's sarcoma-associated herpesvirus (KSHV), the most recently discovered human tumor virus, is associated with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The K9 open reading frame of KSHV encodes a viral interferon (IFN) regulatory factor (vIRF) which functions as a repressor for cellular IFN-mediated signal transduction and as an oncoprotein to induce cell growth transformation. Here, we demonstrate that KSHV vIRF interacts with the cellular p53 tumor suppressor through the putative DNA binding region of vIRF and the central region of p53. This interaction suppresses the level of phosphorylation and acetylation of p53 and inhibits transcriptional activation of p53. As a consequence, vIRF efficiently prevents p53-mediated apoptosis. These results suggest that KSHV vIRF interacts with and inhibits the p53 tumor suppressor to circumvent host growth surveillance and to facilitate uncontrolled cell proliferation.

* Corresponding author. Mailing address: Tumor Virology Division, New England Regional Primate Research Center, Harvard Medical School, 1 Pine Hill Dr., Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508) 786-1416. E-mail: jae_jung{at}hms.harvard.edu.

dagger Present address: Genetic Therapy, Inc., Gaithersburg, MD 20878.

Journal of Virology, August 2001, p. 7572-7582, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7572-7582.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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