title: Hepatitis B virus X protein stimulates the Hedgehog-Gli activation through protein stabilization and nuclear localization of Gli1 in liver cancer cells.
abstract: Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, which frequently results in hepatits, cirrhosis, fibrosis, and ultimately hepatocellular carcinoma (HCC). Recent studies have shown the activation of Hedgehog signaling in HCC. Here, we provide evidences that HBV induces Gli-directed gene transactivation. HBx increases the protein stability of Gli proteins, which are key transcription factors of the Hedgehog signaling pathway, and nucleus translocation of Gli1 through direct protein interaction of HBx and Gli1. This functional synergism of Gli1 protein by HBx increases the Hedgehog activation-directed gene expression. Taken together, these results suggest that HBV infection might induce hepatocellular carcinoma by modulating post-translational activation of the hedgehog signaling components.
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
authors: Hye Young
authors: HY
authors: Kim
authors: Hyun Kook
authors: HK
authors: Cho
authors: Sung Pyo
authors: SP
authors: Hong
authors: Jaehun
authors: J
authors: Cheong
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000378:metabolism*; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D000071676:Zinc Finger Protein GLI1; C057628:hepatitis B virus X protein