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Originally published In Press as doi:10.1074/jbc.M312801200 on January 24, 2004

J. Biol. Chem., Vol. 279, Issue 16, 16822-16831, April 16, 2004
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Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus*

Joseph H. Jeong{ddagger}, Joshua Orvis, Jong Wook Kim, Curtis P. McMurtrey, Rolf Renne§, and Dirk P. Dittmer||¶

From the University of Oklahoma Health Sciences Center, Department of Microbiology and Immunology, Oklahoma City, Oklahoma 73104 §Case Western Reserve University, Cleveland, Ohio 44106 and ||University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 has been established as the etiological agent of Kaposi's sarcoma and certain AIDS-associated lymphomas. KSHV establishes latent infection in these tumors, invariably expressing high levels of the viral latency-associated nuclear antigen (LANA) protein. LANA is necessary and sufficient to maintain the KSHV episome. It also modulates viral and cellular transcription and has been implicated directly in oncogenesis because of its ability to bind to the p53 and pRb tumor suppressor proteins. Previously, we identified the LANA promoter (LANAp) and showed that it was positively regulated by LANA itself. Here, we present a detailed mutational analysis and define cis-acting elements and trans-acting factors for the core LANAp. We found that a downstream promoter element, TATA box, and GC box/Sp1 site at -29 are all individually required for activity. This architecture places LANAp into the small and unusual group of eukaryotic promoters that contain both the downstream promoter element and TATA element but lack a defined initiation site. Furthermore, we demonstrate that LANA regulates its own promoter via its C-terminal domain and does bind to a defined site within the core promoter.


Received for publication, November 24, 2003 , and in revised form, January 20, 2004.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} Present address: Dana-Farber Cancer Institute, Harvard University, Boston, MA 02115.

To whom correspondence should be addressed: University of Oklahoma Health Sciences Center, Dept. of Microbiology and Immunology, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104. Tel.: 405-271-2133 (ext. 46645); Fax: 405-271-3117; E-mail: dirk-dittmer{at}ouhsc.edu.


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