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  The PreS2 activator MHBst of hepatitis B virus activates c- raf-1/Erk2 signaling in transgenic mice

Hildt, E., Munz, B., Saher, G., Reifenberg, K., & Hofschneider, P. H. (2002). The PreS2 activator MHBst of hepatitis B virus activates c- raf-1/Erk2 signaling in transgenic mice. EMBO Journal, 21(4), 525-535.

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Genre: Journal Article
Alternative Title : Embo J.

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 Creators:
Hildt, E.1, Author              
Munz, B.1, Author              
Saher, G.1, Author              
Reifenberg, K., Author
Hofschneider, P. H.1, Author              
Affiliations:
1Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              

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Free keywords: hepatitis B virus; hepatocellular carcinoma; signal transduction; surface proteins; transgenics
 Abstract: The large hepatitis B virus (HBV) surface protein (LHBs) and C- terminally truncated middle size surface proteins (MHBs(t)) form the family of the PreS2 activator proteins of HBV. Their transcriptional activator function is based on the cytoplasmic orientation of the PreS2 domain. MHBs(t) activators are paradigmatic for this class of activators. Here we report that MHBs(t) is protein kinase C (PKC)-dependently phosphorylated at Ser28. The integrity of the phosphorylation site is essential for the activator function. MHBs(t) triggers PKC-dependent activation of c-Raf-1/Erk2 signaling that is a prerequisite for MHBs(t)-dependent activation of AP-1 and NF-kappaB. To analyze the pathophysiological relevance of these data in vivo, transgenic mice were established that produce the PreS2 activator MHBs(t) specifically in the liver. In these mice, a permanent PreS2-dependent specific activation of c-Raf-1/Erk2 signaling was observed, resulting in an increased hepatocyte proliferation rate. In transgenics older than 15 months, an increased incidence of liver tumors occurs. These data suggest that PreS2 activators LHBs and MHBs(t) exert a tumor promoter- like function by activation of key enzymes of proliferation control.

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Language(s): eng - English
 Dates: 2002-02-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 39056
ISI: 000174014700005
 Degree: -

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Title: EMBO Journal
  Alternative Title : Embo J.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 21 (4) Sequence Number: - Start / End Page: 525 - 535 Identifier: ISSN: 0261-4189