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Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association
1Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Abstract:
Chronic active hepatitis caused by infection with hepatitis B virus, a DNA virus, is a major risk factor for human hepatocellular carcinoma. Since the oncogenicity of several DNA viruses is dependent on the interaction of their viral oncoproteins with cellular tumor-suppressor gene products, we investigated the interaction between hepatitis B virus X protein (HBX) and human wild-type p53 protein. HBX complexes with the wild-type p53 protein and inhibits its sequence-specific DNA binding in vitro. HBX expression also inhibits p53-mediated transcriptional activation in vivo and the in vitro association of p53 and ERCC3, a general transcription factor involved in nucleotide excision repair. Therefore, HBX may affect a wide range of p53 functions and contribute to the molecular pathogenesis of human hepatocellular carcinoma.
Insights
Hepatitis B virus X protein (HBX) interacts with and inhibits the tumor suppressor protein p53. This interaction disrupts p53
Area of Science:
- Molecular biology
- Virology
- Oncology
Background:
- Chronic hepatitis B virus infection is a significant risk factor for hepatocellular carcinoma.
- The oncogenic potential of DNA viruses often involves viral oncoproteins interacting with cellular tumor suppressors.
Purpose of the Study:
- To investigate the interaction between hepatitis B virus X protein (HBX) and human wild-type p53.
- To determine if HBX affects p53's function in transcriptional activation and DNA binding.
Main Methods:
- In vitro complex formation assays.
- In vivo transcriptional activation assays.
- In vitro association studies with transcription factors.
Main Results:
- Hepatitis B virus X protein (HBX) forms complexes with wild-type p53 protein.
- HBX inhibits p53's sequence-specific DNA binding in vitro.
- HBX suppresses p53-mediated transcriptional activation in vivo.
- HBX interferes with the association of p53 and ERCC3, a DNA repair transcription factor.
Conclusions:
- HBX interacts with and inhibits the function of the tumor suppressor p53.
- HBX may disrupt multiple p53-dependent cellular processes.
- HBX's interference with p53 function likely contributes to hepatocellular carcinoma development.