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
| Autor: | Seok Hee Park, Youngsuk Yi, W. Tony Parks, Hye Seong Cho, Seong-Jin Kim, Cecile Lee, Yosef Shaul, Anita B. Roberts, Shin Geon Choi, Mark P. de Caestecker, Dug Keun Lee |
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| Rok vydání: | 2001 |
| Předmět: |
Liver Cirrhosis
Transcriptional Activation Hepatitis B virus Cirrhosis Biology medicine.disease_cause Pathogenesis Mice Transforming Growth Factor beta Fibrosis Genetics medicine Animals Smad4 Protein Cell Nucleus 3T3 Cells Oncogene Proteins Viral Transforming growth factor beta Hepatitis B medicine.disease DNA-Binding Proteins Hepatocellular carcinoma Immunology Trans-Activators biology.protein Hepatic fibrosis Protein Binding Signal Transduction Research Paper Developmental Biology |
| Zdroj: | Genes & Development. 15:455-466 |
| ISSN: | 1549-5477 0890-9369 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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