Transcriptional repression of the human p53 gene by hepatitis B viral X protein

Hepatitis B viral X protein (HBx) and the human p53 protein (p53) have been known as a transactivator and as a tumor suppressor, respectively. These two proteins have also been known to interact with each other to neutralize their authentic functions and the p53 represses the HBV enhancer/X promoter activity. Here we report that the promoter activity of the human p53 gene was strongly repressed by the HBx using the chloramphenicol acetyl transferase (CAT) assay. Analyses of serial deletion, site-directed mutagenesis and the heterologous promoter system showed that the site responsible for the repression was the E-box element in the promoter of the p53 gene. In addition, HBx as expected also repressed the activation of the p53 promoter by c-Myc through the E-box element. Northern blot analyses also showed that the expression of the p53 gene in the HepG2-K8 cell line, which expresses HBV genes including HBx, was much more repressed than that of the control cell HepG2. These results with previous data suggest that the shift of the reciprocal inhibitory activities at the levels of protein-protein interaction and transcription between HBx and p53 may play a decisive role in the HBV-related hepatocarcinogenesis.