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

Biochem Biophys Res Commun. 2005 Dec 23;338(3):1551-6. doi: 10.1016/j.bbrc.2005.10.117. Epub 2005 Nov 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis*
  • Cell Line, Tumor
  • Hepatitis B virus* / genetics
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Viral Regulatory and Accessory Proteins
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • RNA, Messenger
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • bcl-2-Associated X Protein
  • hepatitis B virus X protein