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Biochem Biophys Res Commun. 2005 Dec 23;338(3):1551-6. Epub 2005 Nov 2.

Human hepatitis B virus X protein induces apoptosis in HepG2 cells: role of BH3 domain.

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School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive 05N-10, Singapore 637551, Singapore.


The smallest protein of hepatitis B virus, HBX, has been implicated in the development of liver diseases by interfering with normal cellular processes. Its role in cell proliferation has been unclear as both pro-apoptotic and anti-apoptotic activities have been reported. We showed molecular evidence that HBX induced apoptosis in HepG2 cells. A Bcl-2 Homology Domain 3 was identified in HBX, which interacted with anti-apoptotic but not pro-apoptotic members of the Bcl-2 family of proteins. HBX induced apoptosis when transfected into HepG2 cells, as demonstrated by both flow cytometry and caspase-3 activity. However, HBX protein may not be stable in apoptotic cells triggered by its own expression as only its mRNA or the fusion protein with the glutathione-S-transferase was detected in transfected cells. Our results suggested that HBX behaved as a pro-apoptotic protein and was able to induce apoptosis.

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