PMID- 1639069
OWN - NLM
STAT- MEDLINE
DCOM- 19920828
LR  - 20220511
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 11
IP  - 8
DP  - 1992 Aug
TI  - Hepatitis B virus transactivator MHBst: activation of NF-kappa B, selective 
      inhibition by antioxidants and integral membrane localization.
PG  - 2991-3001
AB  - 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.
FAU - Meyer, M
AU  - Meyer M
AD  - Max-Planck-Institute for Biochemistry, Department of Virus Research, Martinsried, 
      Germany.
FAU - Caselmann, W H
AU  - Caselmann WH
FAU - Schluter, V
AU  - Schluter V
FAU - Schreck, R
AU  - Schreck R
FAU - Hofschneider, P H
AU  - Hofschneider PH
FAU - Baeuerle, P A
AU  - Baeuerle PA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Antioxidants)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Pyrrolidines)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Thiocarbamates)
RN  - 0 (Trans-Activators)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Chloramphenicol O-Acetyltransferase/genetics/metabolism
MH  - Fluorescent Antibody Technique
MH  - HeLa Cells
MH  - Hepatitis B Surface Antigens/genetics/*metabolism
MH  - Hepatitis B virus/drug effects/*genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Oligodeoxyribonucleotides
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Pyrrolidines/*pharmacology
MH  - Recombinant Fusion Proteins/metabolism
MH  - Thiocarbamates/*pharmacology
MH  - Trans-Activators/genetics/*metabolism
MH  - Transfection
PMC - PMC556781
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
PMCR- 1993/08/01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
PHST- 1993/08/01 00:00 [pmc-release]
AID - 10.1002/j.1460-2075.1992.tb05369.x [doi]
PST - ppublish
SO  - EMBO J. 1992 Aug;11(8):2991-3001. doi: 10.1002/j.1460-2075.1992.tb05369.x.