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Hepatitis B virus transactivator MHBst: activation of NF‐kappa B, selective inhibition by antioxidants and integral membrane localization.
Author(s) -
Meyer M.,
Caselmann W.H.,
Schlüter V.,
Schreck R.,
Hofschneider P.H.,
Baeuerle P.A.
Publication year - 1992
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1992.tb05369.x
Subject(s) - biology , transactivation , nfkb1 , kappa , virology , hepatitis b virus , virus , microbiology and biotechnology , biochemistry , gene , gene expression , transcription factor , linguistics , philosophy
C‐terminal truncation of the middle surface antigen from hepatitis B virus (MHBs) gives rise to a novel transactivating protein, called MHBst. In this study we show that MHBst like the HBx protein of HBV, can cause nuclear appearance of NF‐kappa B DNA binding activity and induce various kappa B‐controlled reporter genes. While an inhibitor of protein kinase C could not block gene induction by MHBst, the antioxidants N‐acetyl‐L‐cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) could potently suppress transactivation at mM and microM concentrations, respectively. Also, kappa B‐dependent gene induction by the transactivator HBx was blocked. The effects were selective because PDTC did not interfere with MHBst and HBx‐induced activation of the c‐fos promoter/enhancer, nor with the basal activity of several other reporter genes lacking functional NF‐kappa B binding motifs. Our data suggest that induction of a prooxidant state is crucial for the activation of NF‐kappa B by MHBst and HBx and might be related to the hepatocarcinogenic potential of the viral proteins. MHBst had a subcellular localization unusual for a viral transactivator: it appeared to be an integral membrane protein of the endoplasmic reticulum.