PX, THE HBV-ENCODED COACTIVATOR, SUPPRESSES THE PHENOTYPES OF TBP ANDTAF(II)250 MUTANTS

Hepatitis B virus (HBV) infects humans and causes a wide range of clin ical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation mach inery. Accordingly, the HBV-encoded pX, the only known viral regulator , is a potent transcription coactivator. We investigated the relations hip between pX and cellular coactivators. We show that pX restores wil d-type activity to inactive TBPAS mutants with poor TAF(II)250 and act ivator-binding activity. This pX-mediated recovery, however, is not ob tained with inactive TBPAS mutants in binding of other general transcr iption factors. Remarkably, ts13, a cell line temperature sensitive fo r TAF(II)250 function, exhibiting growth arrest and apoptosis at the r estrictive temperature, is rescued partially by pX expression, thus ge nerating a pX-dependent cell growth. Collectively, our results suggest that pX suppresses some of the phenotypes of TBP and TAF(II)250 mutat ions, implying that pX circumvents the need for a holo-TFIID complex f or transcription activation to proceed.