title: Hepatitis B virus X protein induces lipogenic transcription factor SREBP1 and fatty acid synthase through the activation of nuclear receptor LXRalpha.
abstract: HBV (hepatitis B virus) is a primary cause of chronic liver disease, which frequently results in hepatitis, cirrhosis and ultimately HCC (hepatocellular carcinoma). Recently, we showed that HBx (HBV protein X) expression induces lipid accumulation in hepatic cells mediated by the induction of SREBP1 (sterol-regulatory-element-binding protein 1), a key regulator of lipogenic genes in the liver. However, the molecular mechanisms by which HBx increases SREBP1 expression and transactivation remain to be clearly elucidated. In the present study, we demonstrated that HBx interacts with LXRalpha (liver X receptor alpha) and enhances the binding of LXRalpha to LXRE (LXR-response element), thereby resulting in the up-regulation of SREBP1 and FAS (fatty acid synthase) in the presence or absence of the LXR agonist T0901317 in the hepatic cells and HBx-transgenic mice. Furthermore, HBx also augments the ability to recruit ASC2 (activating signal co-integrator 2), a transcriptional co-activator that controls liver lipid metabolic pathways, to the LXRE with LXRalpha. These studies place LXRalpha in a key position within the HBx-induced lipogenic pathways, and suggest a molecular mechanism through which HBV infection can stimulate the SREBP1-mediated control of hepatic lipid accumulation.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Kyeongjin
authors.initials: K
authors.lastname: Kim
authors.forename: Kook Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Hyeong Hoe
authors.initials: HH
authors.lastname: Kim
authors.forename: Jaehun
authors.initials: J
authors.lastname: Cheong
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D005234:Fatty Liver / Q000209:etiology; D017930:Genes, Reporter; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity; D008055:Lipids / Q000502:physiology; D008113:Liver Neoplasms; D000071518:Liver X Receptors; D051379:Mice; D008822:Mice, Transgenic; D057093:Orphan Nuclear Receptors; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis*; D013449:Sulfonamides / Q000633:toxicity; D015534:Trans-Activators; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D004268:DNA-Binding Proteins; D064429:Fatty Acid Synthases; D006845:Hydrocarbons, Fluorinated; D008055:Lipids; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; C497387:SREBF1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C057628:hepatitis B virus X protein