Pro-apoptotic or anti-apoptotic property of X protein of hepatitis B virus is determined by phosphorylation at Ser31 by Akt

Wei-Ping Lee; Keng-Hsin Lan; Chung-Pin Li; Yee Chao; Han-Chieh Lin; Shou-Dong Lee

doi:10.1016/j.abb.2012.08.008

Pro-apoptotic or anti-apoptotic property of X protein of hepatitis B virus is determined by phosphorylation at Ser31 by Akt

Arch Biochem Biophys. 2012 Dec 15;528(2):156-62. doi: 10.1016/j.abb.2012.08.008. Epub 2012 Sep 13.

Authors

Wei-Ping Lee¹, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Han-Chieh Lin, Shou-Dong Lee

Affiliation

¹ Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan. wplee@vghtpe.gov.tw

PMID: 22982405
DOI: 10.1016/j.abb.2012.08.008

Abstract

The X protein of hepatitis B virus (HBx) has been specifically implicated in either pro-apoptotic or anti-apoptotic activity in an experimental system, but the underlying mechanism is yet uncertain. Activations of survival and proliferation signaling pathways appear to account partly for its anti-apoptotic property. Change in mitochondrial membrane potential may be responsible for its apoptotic property. In this study, we isolated two HBx isoforms from an HBV carrier, one of which contains Akt phosphorylation site at Ser31 and functions as an anti-apoptotic protein (designated HBx-S31). The other does not contain Akt phosphorylation site and functions as an apoptotic protein (designated HBx-L31). HBx-S31 can activate Akt, whereas HBx-L31 cannot; the former enhances tumor growth, whereas the latter suppresses tumorigenesis. Our study provides evidence that HBx plays dual roles, namely pro-apoptotic and anti-apoptotic, through different isoforms in which HBx with Ser31 transduces survival signal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Amino Acid Substitution
Apoptosis / physiology*
Apoptosis Regulatory Proteins / chemistry
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / physiology
Binding Sites
HEK293 Cells
Hep G2 Cells
Hepatitis B virus / genetics
Hepatitis B virus / pathogenicity*
Hepatitis B virus / physiology*
Humans
Molecular Sequence Data
Mutagenesis, Site-Directed
Phosphorylation
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / physiology
Proto-Oncogene Proteins c-akt / metabolism
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Serine / chemistry
Signal Transduction
Trans-Activators / chemistry
Trans-Activators / genetics
Trans-Activators / physiology*
Viral Regulatory and Accessory Proteins

Substances

Apoptosis Regulatory Proteins
Protein Isoforms
Recombinant Proteins
Trans-Activators
Viral Regulatory and Accessory Proteins
hepatitis B virus X protein
Serine
Proto-Oncogene Proteins c-akt