The X-gene of human hepatitis B virus transactivates the c-jun and alpha-fetoprotein genes.
The X-gene product of human hepatitis B virus is a transacting transcriptional factor which activates a variety of heterologous viral and host promoters/enhancers. We have found that the X-gene product can significantly transactivate the regulatory sequences located at the 5'-upstream of the c-jun oncogene when a reporter plasmid containing the sequences was co-transfected to HepG2 cells with an X-gene expression plasmid. The results of mutational analysis indicate that the X-gene activation requires the AP-1 sequence of the c-jun gene. Furthermore, we also found that the X-gene is capable of activating the 5'-upstream sequence of the alpha-fetoprotein gene. There are at least two elements that respond to the X-gene transactivation. One is located in the sequences between -5,100 and -2,900, and the other is at the C/EBP site. Therefore, the X-gene activates the c-jun and alpha-fetoprotein genes through different host factors, namely AP-1 and C/EBP, respectively. The results of c-jun activation by the X-gene strongly support the previous hypothesis that the X-gene may play a critical role in the development of hepatocellular carcinoma.
Zhou
M X
MX
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield.
Watabe
M
M
Watabe
K
K
D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005814:Genes, Viral; D006511:Hepatitis B Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins; D000509:alpha-Fetoproteins / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D006511:Hepatitis B Antigens; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D000509:alpha-Fetoproteins; C057628:hepatitis B virus X protein; D004247:DNA