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

Ralph Schuster, Eberhardt Hildt, Shau Feng Chang, Olivier Terradillos, Teresa Pollicino, Robert Lanford, Wolfram H. Gerlich, Hans Will, Stephan Schaefer

    Research output: Contribution to journalArticlepeer-review

    19 Scopus citations

    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 avihepadnavirai 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.

    Original languageEnglish (US)
    Pages (from-to)6606-6613
    Number of pages8
    JournalOncogene
    Volume21
    Issue number43
    DOIs
    StatePublished - 2002

    Keywords

    • Apoptosis
    • Avihepadnavirus
    • DHBV
    • HBx
    • HCC
    • Transactivation

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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