Conserved transactivating and pro-apoptotic functions of hepadnaviral X protein in ortho- and avihepadnaviruses
- 23 September 2002
- journal article
- Published by Springer Nature in Oncogene
- Vol. 21 (43) , 6606-6613
- https://doi.org/10.1038/sj.onc.1205916
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.Keywords
This publication has 74 references indexed in Scilit:
- Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosisOncogene, 2001
- Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosisOncogene, 2001
- Duck Hepatitis B Virus Expresses a Regulatory HBx-Like Protein from a Hidden Open Reading FrameJournal of Virology, 2001
- Correct binding of viral X protein to UVDDB-p127 cellular protein is critical for efficient infection by hepatitis B virusesOncogene, 2000
- Hepatitis B Virus X Protein Inhibits Transforming Growth Factor-β-induced Apoptosis through the Activation of Phosphatidylinositol 3-Kinase PathwayJournal of Biological Chemistry, 2000
- Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblastsOncogene, 2000
- The Hepatitis B Virus HBx Protein Inhibits Caspase 3 ActivityJournal of Biological Chemistry, 1998
- Analysis of the Tumorigenicity of the X Gene of Hepatitis B Virus in A Nontransformed Hepatocyte Cell Line and the Effects of Cotransfection With A Murine P53 Mutant Equivalent to Human Codon 249Hepatology, 1996
- The × Gene of Hepatitis B Virus Induced Growth Stimulation and Tumorigenic Transformation of Mouse NIH3T3 CellsJapanese Journal of Cancer Research, 1989
- VIRUS-LIKE PARTICLES IN SERUM OF PATIENTS WITH AUSTRALIA-ANTIGEN-ASSOCIATED HEPATITISThe Lancet, 1970