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TORC1 and TORC2 Coactivators Are Required for Tax Activation of the Human T-Cell Leukemia Virus Type 1 Long Terminal Repeats

Yeung-Tung Siu,^1, King-Tung Chin,^1, Kam-Leung Siu,¹ Elizabeth Yee Wai Choy,¹ Kuan-Teh Jeang,² and Dong-Yan Jin^1*

Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong,¹ Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, 9000 Rockville Pike, Bethesda, Maryland 20892-0460²

Received 15 January 2006/ Accepted 28 April 2006

Human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription from the long terminal repeats (LTR). Mechanisms through which Tax activates LTR have been established, but coactivators of this process remain to be identified and characterized. Here we show that all three members of the TORC family of transcriptional regulators are coactivators of Tax for LTR-driven expression. TORC coactivation requires CREB, but not ATF4 or other bZIP factors. Tax physically interacts with TORC1, TORC2, and TORC3 (TORC1/2/3), and the depletion of TORC1/2/3 inhibited Tax activity. TORC coactivation can be further enhanced by transcriptional coactivator p300. In addition, coactivators in the p300 family are required for full activity of Tax independently of TORC1/2/3. Thus, both TORC and p300 families of coactivators are essential for optimal activation of HTLV-1 transcription by Tax.

These authors contributed equally to this work.

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