The hepatitis B virus X protein is a co-activator of activated transcription that modulates the transcription machinery and distal binding activators.
Hepatitis B virus X protein (HBx) transactivates viral and cellular genes through a wide variety of cis-elements, but the mechanism has not been well elucidated. Evidence for nuclear events in HBx transactivation has been reported. Here we examine the role of HBx in modulation of transcription with a transient transfection system and an in vitro transcription assay. Reporters bearing Gal4-binding sites were applied to avoid the effects of endogenous transcription factors with or without signaling processes. The Gal4-DNA binding domain fused form of HBx exhibited no effect on Gal4-responsive reporters. However, HBx augmented activated transcription by transcriptional activators, suggesting HBx retains a co-activator but not a transcriptional activator function. The functional domain for co-activation was the same as that for HBx transactivation, and the transcription factor IIB- and RNA polymerase II subunit 5-interacting sites of HBx, which were critical for HBx transactivation, were shown to be crucial for the co-activation function. Importantly, HBx stimulated transcription on templates bearing the X responsive elements in vitro with endogenous activators. These results imply that HBx acts as a co-activator that modulates transcriptional machinery and distal-binding activators, which may explain one of the mechanisms of transactivation by HBx when localized in nuclei.
Department of Molecular Biology, Cancer Research Institute, Kanazawa University, Takara-machi 13-1, Kanazawa 920-0934, Japan.
Y
Y
Lin
H
H
Tang
T
T
Nomura
D
D
Dorjsuren
N
N
Hayashi
W
W
Wei
T
T
Ohta
R
R
Roeder
S
S
Murakami
D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics*; D008957:Models, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D005656:Fungal Proteins; C070633:Gal-VP16; D011994:Recombinant Proteins; D015534:Trans-Activators; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D012321:DNA-Directed RNA Polymerases