title: Hepatic STAMP2 decreases hepatitis B virus X protein-associated metabolic deregulation.
abstract: Six transmembrane protein of prostate 2 (STAMP2) plays a key role in linking inflammatory and diet-derived signals to systemic metabolism. STAMP2 is induced by nutrients/feeding as well as by cytokines such as TNFα, IL-1β, and IL-6. Here, we demonstrated that STAMP2 protein physically interacts with and decreases the stability of hepatitis B virus X protein (HBx), thereby counteracting HBx-induced hepatic lipid accumulation and insulin resistance. STAMP2 suppressed the HBx-mediated transcription of lipogenic and adipogenic genes. Furthermore, STAMP2 prevented HBx-induced degradation of IRS1 protein, which mediates hepatic insulin signaling, as well as restored insulin-mediated inhibition of gluconeogenic enzyme expression, which are gluconeogenic genes. We also demonstrated reciprocal expression of HBx and STAMP2 in HBx transgenic mice. These results suggest that hepatic STAMP2 antagonizes HBx-mediated hepatocyte dysfunction, thereby protecting hepatocytes from HBV gene expression.
authors.affiliation: Department of Molecular Biology College of Natural Sciences Pusan National University Busan 609-735, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Hyun Kook
authors.initials: HK
authors.lastname: Cho
authors.forename: Seong Keun
authors.initials: SK
authors.lastname: Yoo
authors.forename: Jae Hun
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000818:Animals; D005260:Female; D015870:Gene Expression; D005943:Gluconeogenesis / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010088:Oxidoreductases / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D011972:Receptor, Insulin / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D008565:Membrane Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D010088:Oxidoreductases; C503310:STEAP4 protein, human; D011972:Receptor, Insulin