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

Dug Keun Lee, Seok Hee Park, Youngsuk Yi, Shin Geon Choi, Cecile Lee, W. Tony Parks, Hye Seong Cho, Mark P. De Caestecker, Yosef Shaul, Anita B. Roberts, Seong Jin Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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-β 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-β signaling. We show that pX enhances transcriptional activity in response to TGF-β, 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-β 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.

Original languageEnglish (US)
Pages (from-to)455-466
Number of pages12
JournalGenes and Development
Volume15
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Fibrosis
  • Hepatitis B virus pX
  • Signaling
  • Smad
  • TGF-β

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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