Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of HTLV-I LTR

Abstract

HTLV-I Tax is pivotally involved in leukemogenesis, and it potently transactivates viral transcription from the LTR. Mechanisms through which Tax activates LTR have been established, but coactivators of this process remain to be identified and characterized. We have recently shown that all three members of the newly identified 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, relocating them to specific intranuclear subdomains. a chromatin immunoprecipitation assay indicates an association of TORC1, TORC2, and TORC3 with the 21-bp repeats of the HTLV-1 LTR. Depletion of TORC coactivators was accomplished using RNAi-inhibited Tax-dependent transcriptional activation of HTLV-1 LTR. Thus, TORC members are essential Tax coactivators for viral transcription.