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  • Original Paper
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Conserved transactivating and pro-apoptotic functions of hepadnaviral X protein in ortho- and avihepadnaviruses

Oncogene volume 21, pages 6606–6613 (2002)Cite this article

Abstract

Two established activities of the multifunctional human hepatitis B virus X-protein are its transactivating and pro-apoptotic potential. We analysed whether X-proteins from other orthohepadnaviruses and the newly discovered avihepadnaviral X-proteins have similar functions as HBx. Previously, we have shown that HBx suppresses oncogenic transformation of primary rat embryo fibroblasts (REF) by induction of apoptosis. Using this system, we found that the wildtype X-proteins of woodchuck, ground squirrel, arctic squirrel and woolly monkey hepatitis B virus exhibit similar levels of pro-apoptotic activity as HBx, whereas mutants with carboxyterminal deletions were severely impaired in this activity. A strong correlation between the pro-apoptotic and transactivating abilities of the mammalian X-proteins was found. The newly discovered avihepadnaviral X-like proteins showed similar and Raf-MAPK pathway-dependent transactivating abilities and induced apoptosis in the REF-assay. Our data indicate that the transactivating and pro-apoptotic activities reside in the carboxyterminal half of orthohepadnaviral X and are conserved in avihepadnaviral X-proteins.

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Acknowledgements

We thank B Luber (c-Ha-ras and c-myc), CW Distelhorst (Bcl-2) and E White (E1B) for providing the indicated constructs.

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Author notes

  1. Stephan Schaefer

    Present address: Department of Virology, University of Rostock, Schillingallee 70, Rostock, D-18055, Germany

  2. Ralph Schuster: DLR Projektträger des BMBF, Bonn, Germany

Authors and Affiliations

  1. Institute for Medical Virology, JLU Gießen, Germany

    Ralph Schuster, Wolfram H Gerlich & Stephan Schaefer

  2. Robert Koch Institute, Berlin, Germany

    Eberhardt Hildt

  3. Heinrich Pette Institute, Hamburg, Germany

    Shau-Feng Chang & Hans Will

  4. Pasteur Institute, Paris, France

    Olivier Terradillos & Teresa Pollicino

  5. Southwest Foundation for Biomedical Research, San Antonio, Texas, USA

    Robert Lanford

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Correspondence to Stephan Schaefer.

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Schuster, R., Hildt, E., Chang, SF. et al. Conserved transactivating and pro-apoptotic functions of hepadnaviral X protein in ortho- and avihepadnaviruses. Oncogene 21, 6606–6613 (2002). https://doi.org/10.1038/sj.onc.1205916

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