title: Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic             cell line by sequestering SIRT1 deacetylase.
abstract: Hepatitis B virus X (HBX) protein has been reported to induce upregulation             of β-catenin, a known proto-oncogene, in p53-knockout and p53-mutant hepatic cell             lines both in a GSK-3β-dependent manner and via interaction with adenomatous polyposis             coli, which results in protection from β-catenin degradation. In this study, we             describe a novel mechanism for HBX-mediated upregulation of β-catenin. We observed             that HBX interacts with SIRT1, a class III histone deacetylase. Furthermore, the             presence of HBX attenuated the interaction between SIRT1 and β-catenin, leading             to protection of β-catenin from the inhibitory action of SIRT1. Reduction of SIRT1             with siRNA or suppression of SIRT1 activity with nicotinamide upregulated β-catenin             protein levels. In contrast, enhancement of SIRT1 activity with resveratrol reduced             β-catenin protein levels. Furthermore, in Hep3B cells stably expressing HBX, overexpression             of SIRT1 or treatment with resveratrol enhanced sensitivity to doxorubicin-induced             apoptosis, indicating that upregulation of SIRT1 could be a therapeutic strategy             for HBV-related hepatocellular carcinoma. Based on these results, we propose that             HBX upregulates β-catenin by sequestering SIRT1, which leads to anticancer drug             treatment resistance.
authors.affiliation: WCU, Department of Cogno-Mechatronics Engineering, Pusan National                     University, Busan, Republic of Korea.
authors.forename: Ratakorn
authors.initials: R
authors.lastname: Srisuttee
authors.forename: Sang Seok
authors.initials: SS
authors.lastname: Koh
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Waraporn
authors.initials: W
authors.lastname: Malilas
authors.forename: Wassamon
authors.initials: W
authors.lastname: Boonying
authors.forename: Il-Rae
authors.initials: IR
authors.lastname: Cho
authors.forename: Byung Hak
authors.initials: BH
authors.lastname: Jhun
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Horio
authors.forename: Edward
authors.initials: E
authors.lastname: Seto
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D056564:Sirtuin 1 / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D051176:beta Catenin; C057628:hepatitis B virus X protein; D004317:Doxorubicin; C447939:SIRT1 protein, human; D056564:Sirtuin 1