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

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.