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Hepatitis B virus transactivator HBx uses a tumour promoter signalling pathway

Nature volume 361, pages 742–745 (1993)Cite this article

Abstract

THE hepatitis B virus (HBV) transactivator protein HBx is enigmatic in that it stimulates a striking variety of promoters which do not share a common cis-regulatory element1–5. As it does not bind to DNA6,7, it has been speculated that HBx acts indirectly through cellular pathways4,6–8. Under certain conditions HBx can have an oncogenic potential, which may be relevant for HBV-associated liver carcinogenesis9–11, but until now the mechanism for transactivation and cell transformation by HBx was unclear. We report here that HBx uses a complex signal transduction pathway for transactivation. An increase in the endogenous protein kinase C (PKC) activator sn-l,2-diacylglycerol and the subsequent activation of PKC give rise to activation of the transcription factor AP-1 (Jun–Fos). As a result, HBx transactivates through binding sites for AP-1 and other PKC-dependent transcription factors (AP-2, NF-κB), thereby explaining the as-yet incomprehensible variety of HBx-inducible genes. As the PKC signal cascade also mediates cell transformation by tumour-promoting agents, the mechanism presented here might account for the oncogenic potential of HBx.

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Authors and Affiliations

  1. Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-8033, Martinsried, Germany

    Alexander S. Kekulé, Ulrich Lauer, Ludwig Weiss, Birgit Luber & Peter Hans Hofschneider

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  1. Alexander S. Kekulé
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  2. Ulrich Lauer
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  3. Ludwig Weiss
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  4. Birgit Luber
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  5. Peter Hans Hofschneider
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Kekulé, A., Lauer, U., Weiss, L. et al. Hepatitis B virus transactivator HBx uses a tumour promoter signalling pathway. Nature 361, 742–745 (1993). https://doi.org/10.1038/361742a0

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