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  • Original Paper
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HBV transcription repression in response to genotoxic stress is p53-dependent and abrogated by pX

Oncogene volume 18, pages 7506–7513 (1999)Cite this article

Abstract

Transcription of hepatitis B Virus (HBV), an important risk factor of hepatocellular carcinoma (HCC), is controlled by cellular transcription activators including some of the cellular signaling targets. Consequently, HBV transcription rate changes in response to the cellular physiological conditions. In this report we investigated HBV gene expression and the role of physiological levels of the viral X protein (pX) under cisplatin induced genotoxic stress. We show that under these conditions the RNA level of an HBV mutant which does not express pX is sharply reduced. Studies revealed that transcription repression is responsible for the observed reduction in HBV RNA level. Repression of HBV transcription was obtained only in the p53 proficient cells. Furthermore, HBV transcription rate is recovered by the cotransfected p53 dominant negative plasmid, indicating that p53 is directly responsible for HBV transcription repression. Unexpectedly, p73, the recent p53 homologue, does not repress but rather activates HBV transcription. Interestingly, pX produced either by the HBV genome or by a cotransfected plasmid, relieves the p53 mediated repression. Collectively, these results attribute a physiological role to p53-inactivation by pX, and explain how pX may support HCC development.

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Acknowledgements

We thank Dr M Oren for p53 and DD plasmids and for anti p53 antibodies. This work was supported by a grant from the national council for research and development. Israel and the Deutsches Krebsforschunszentrum (DKFZ).

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  1. Department of Molecular Genetics, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Gilad Doitsh & Yosef Shaul

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  1. Gilad Doitsh
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Doitsh, G., Shaul, Y. HBV transcription repression in response to genotoxic stress is p53-dependent and abrogated by pX. Oncogene 18, 7506–7513 (1999). https://doi.org/10.1038/sj.onc.1203209

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