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Blood, 1 January 2004, Vol. 103, No. 1, pp. 222-228.
Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-05-1538.


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NEOPLASIA

Transcriptional coactivation of c-Jun by the KSHV-encoded LANA

Jiabin An, Yiping Sun, and Matthew B. Rettig

From the VA Greater Los Angeles Healthcare System, Los Angeles, CA; and Department of Medicine, UCLA School of Medicine, Los Angeles, CA.

The Kaposi sarcoma–associated herpesvirus (KSHV)–encoded latency-associated nuclear antigen (LANA) modulates viral and cellular gene expression, including interleukin 6 (IL-6), a growth factor for KSHV-associated diseases. LANA-driven IL-6 expression is dependent on the activator protein 1 (AP1) response element (RE) within the IL-6 promoter. We show that LANA activates the AP1 RE in a Jun-dependent fashion and that LANA enhances the transcriptional activity of a GAL4-Jun fusion protein. Coimmunoprecipitation studies documented a physical interaction between LANA and c-Jun in transiently transfected 293 cells as well as the KSHV-infected BCBL-1 primary effusion lymphoma (PEL) cell line. Taken together, these data indicate that LANA is a transcriptional coactivator of c-Jun. In addition, electrophoretic mobility shift assays demonstrated that LANA induces binding of a c-Jun-Fos heterodimer to the AP1 RE, but does not itself bind to the AP1 RE. RNA interference experiments confirmed that LANA activates the AP1 RE, stimulates binding of a c-Jun-Fos heterodimer to the AP1 RE, and induces expression of IL-6. These data indicate that LANA is a transcriptional coactivator of c-Jun, a function that may have implications for the pathogenesis of KSHV-associated diseases.


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