Specific repression of Tax trans-activation by TAR RNA-binding protein TRBP.

The human T-cell leukemia virus type 1 (HTLV-1)-encoded Tax protein activates transcription from the long terminal repetition via association with host cellular factors. In this study, we searched for cellular proteins that interact with Tax and modulate its activity by using the yeast two-hybrid system. One of the strongest interactors was found to be identical with TRBP, which was previously shown to bind to the RNA encoded by the Tat response element of human immunodeficiency virus type 1. Interactions are demonstrated with Escherichia coli-expressed proteins in vitro and in mammalian cells, using one- and two-hybrid systems, and with antibodies that coprecipitate Tax and TRBP at physiological TRBP concentrations. Moreover, TRBP, when directed into the cytoplasm, is capable of preventing transport of Tax into the nucleus. A 60-amino-acid polypeptide suffices for binding to Tax. TRBP inhibits activation of transcription by both Tax and GAL4-Tax fusion proteins. Inhibition is specific for Tax and is not seen with the other activators tested. Our data are consistent with the interpretation that TRBP inhibits the interplay of Tax with the transcription machinery or accessory factors.