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The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family signaling through direct interaction with Smad4: potential mechanism of hepatitis B virus-induced liver fibrosis.

Authors
Lee, DK; Park, SH; Yi, Y; Choi, SG; Lee, C; Parks, WT; Cho, H; de Caestecker, MP; Shaul, Y; Roberts, AB; Kim, SJ
Citation
Genes & development, 15(4):455-466, 2001
Journal Title
Genes & development
ISSN
0890-93691549-5477
Abstract
Hepatitis B, one of the most common infectious diseases in the world, is closely associated with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Many clinical investigations have revealed that hepatic fibrosis is an important component of these liver diseases caused by chronic hepatitis B. TGF-beta signaling plays an important role in the pathogenesis of fibrosis in chronic hepatitis and cirrhosis. As these diseases are associated with hepatitis B virus (HBV) infection, we examined the possibility that the HBV-encoded pX oncoprotein regulates TGF-beta signaling. We show that pX enhances transcriptional activity in response to TGF-beta, BMP-2, and activin by stabilizing the complex of Smad4 with components of the basic transcriptional machinery. Additionally, confocal microscopic studies suggest that pX facilitates and potentiates the nuclear translocation of Smads, further enhancing TGF-beta signaling. Our studies suggest a new paradigm for amplification of Smad-mediated signaling by an oncoprotein and suggest that enhanced Smad-mediated signaling may contribute to HBV-associated liver fibrosis.
MeSH terms
3T3 CellsAnimalsCell Nucleus/metabolismDNA-Binding Proteins/metabolism*Hepatitis B virus/genetics*Hepatitis B virus/pathogenicityLiver Cirrhosis/virology*MiceOncogene Proteins, Viral/geneticsOncogene Proteins, Viral/metabolismOncogene Proteins, Viral/physiology*Protein BindingSignal Transduction/physiology*Smad4 ProteinTrans-Activators/metabolism*Transcriptional ActivationTransforming Growth Factor beta/metabolism*
DOI
10.1101/gad.856201
PMID
11230153
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
조, 혜성
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