Article

Siu YT, Chin KT, Siu KL, Yee Wai Choy E, Jeang KT, Jin DY.. TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats. J Virol 80: 7052-7059

Department of Biochemistry, The University of Hong Kong, 3/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.
Journal of Virology (Impact Factor: 4.44). 08/2006; 80(14):7052-9. DOI: 10.1128/JVI.00103-06
Source: PubMed

ABSTRACT

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.

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Available from: Kam-Leung Siu, May 20, 2015
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    • "The SIK1-K56M expression vector and the empty vector, pcDNA3, were from Hiroshi Takemori (National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan) [24]. The CRTC1, CRTC2, and CRTC3 vectors as well as the empty vector pcDNA 3.1/V5/HisA were from Dr. Dong-Yan Jin, Department of Biochemistry , The University of Hong Kong [25]. WT CREB (pRc/RSV-Flag- CREB), pRc/RSV-Flag-CREB R314, dominant-negative TORC1 (pcDNA3- TORC1 1-147 -EGFP), and the empty vector pcDNA3-EGFP were from Jean-Rene Cardinaux, University of Lausanne, Lausanne, Switzerland [26]. "
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    • "Additional host factors that directly interact with Tax-1 and act in the Tax-mediated transactivation are the transducer of regulated CREB (TORC) proteins. TORC-1 and TORC-2 are required for Tax activation whereas TORC- 3 enhances Tax-dependent transcription (Koga et al., 2004; Siu et al., 2006). Several cellular factors that interact with Tax and participate to HTLV-1 promoter activation have been identified. "
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    • "Western blotting was carried out as described [13] [28]. Cells were lysed in RIPA buffer (50 mM Tris–HCl, pH 7.4, 150 mM NaCl, 1% Triton X-100, 0.1% SDS, 1% sodium deoxycholate) supplemented with 2 mM PMSF and EDTA-free protease inhibitor cocktail (Roche). "
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