pX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250 mutants.
Hepatitis B virus (HBV) infects humans and causes a wide range of clinical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation machinery. Accordingly, the HBV-encoded pX, the only known viral regulator, is a potent transcription coactivator. We investigated the relationship between pX and cellular coactivators. We show that pX restores wild-type activity to inactive TBPAS mutants with poor TAFII250 and activator-binding activity. This pX-mediated recovery, however, is not obtained with inactive TBPAS mutants in binding of other general transcription factors. Remarkably, ts13, a cell line temperature sensitive for TAFII250 function, exhibiting growth arrest and apoptosis at the restrictive temperature, is rescued partially by pX expression, thus generating a pX-dependent cell growth. Collectively, our results suggest that pX suppresses some of the phenotypes of TBP and TAFII250 mutations, implying that pX circumvents the need for a holo-TFIID complex for transcription activation to proceed.
Haviv
I
I
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100 Israel.
Matza
Y
Y
Shaul
Y
Y
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002460:Cell Line; D006224:Cricetinae; D019925:Cyclin A / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006511:Hepatitis B Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D051548:Histone Acetyltransferases; D006801:Humans; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D013696:Temperature; D015534:Trans-Activators / Q000235:genetics*; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins
D019925:Cyclin A; D004268:DNA-Binding Proteins; D006511:Hepatitis B Antigens; D009687:Nuclear Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa