THE HEPATITIS-B VIRUS LARGE SURFACE PROTEIN (LHBS) IS A TRANSCRIPTIONAL ACTIVATOR

It has been shown that a C-terminally truncated form of the middle-siz ed hepatitis B virus (HBV) surface protein (MHBs(t)) functions as a tr anscriptional activator. This function is dependent on the cytosolic o rientation of the N-terminal PreS2 domain of MHBs(t), but in the case of wild-type MHBs, the PreS2 domain is cotranslationally translocated into the ER lumen. Recent reports demonstrated that the PreS2 domain o f the large HBV surface protein (LHBs) initially remains on the cytoso lic side of the ER membrane after translation. Therefore, the question arose as to whether the LHBs protein exhibits the same transcriptiona l activator function as MHBs(t). We show that LHBs, like MHBs(t), is i ndeed able to activate a variety of promoter elements. There is eviden ce for a PKC-dependent activation of AP-1 and NF-kappa B by LHBs. Down stream of the PKC the functionality of c-Raf-1 kinase is a prerequisit e for LHBs-dependent activation of AP-1 and NF-kappa B since inhibitio n of c-Raf-1 kinase abolishes LHBs-dependent transcriptional activatio n of AP-1 and NF-kappa B. (C) 1996 Academic Press, Inc.