Hepatitis B virus transactivator protein, HBx, associates with the components of TFIIH and stimulates the DNA helicase activity of TFIIH.
Human hepatitis B virus genome encodes a protein, termed HBx, that is widely recognized as a transcriptional transactivator. While HBx does not directly bind cis-acting transcriptional control elements, it has been shown to associate with cellular proteins that bind DNA. Because HBx transactivated a large number of viral/cellular transcriptional control elements, we looked for its targets within the components of the basal transcriptional machinery. This search led to the identification of its interactions with TFIIH. Here, we show that HBx interacts with yeast and mammalian TFIIH complexes both in vitro and in vivo. These interactions between HBx and the components of TFIIH are supported by several lines of evidence including results from immunoprocedures and direct methods of measuring interactions. We have identified ERCC3 and ERCC2 DNA helicase subunits of holoenzyme TFIIH as targets of HBx interactions. Furthermore, the DNA helicase activity of purified TFIIH from rat liver and, individually, the ERCC2 component of TFIIH is stimulated in the presence of HBx. These observations suggest a role for HBx in transcription and DNA repair.
Qadri
I
I
Department of Microbiology, University of Colorado Health Sciences Center, Denver 80262, USA.
Conaway
J W
JW
Conaway
R C
RC
Schaack
J
J
Siddiqui
A
A
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D004789:Enzyme Activation; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D011485:Protein Binding; D051381:Rats; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators / Q000235:genetics*; D035362:Transcription Factor TFIID; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
D029701:Saccharomyces cerevisiae Proteins; C490039:TAF6 protein, S cerevisiae; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051758:Transcription Factor TFIIH; D004265:DNA Helicases