title: The interaction of hepatitis B virus X protein and protein phosphatase type 2 Calpha and its effect on IL-6.
abstract: HBx has been suggested as an important determinant mediating the pathological effects of HBV via interacting with various cellular proteins. To identify new HBx-interacting proteins and elucidate a possible mechanism associated with HBx and HBx-interacting proteins in hepatocellular carcinoma, yeast two-hybrid screening was performed. We identified a novel HBx-interacting protein, serine/threonine protein phosphatase PP2Calpha, and investigated the effects of PP2Calpha on HBx-mediated IL-6 regulation. The interaction between endogenous PP2Calpha, and HBx was confirmed by co-immunoprecipitation. Recombinant HBx dose-dependently reduced enzyme activity of recombinant PP2Calphain vitro. While ectopically expressed PP2Calpha in Cos-7 and Huh-7 cells reduced the expression of IL-6, overexpressed HBx with recombinant HBx-expressing adenovirus overcame PP2Calpha-mediated IL-6 downregulation. In the response of IL-6, HBx phosphorylated STAT3 and recovered PP2Calpha-mediated dephosphorylation of STAT3. These results supported that HBx might play a crucial role in HBV-associated hepatocarcinogenesis even in cases where cells express a negative regulator, PP2Calpha.
authors.affiliation: Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Ji Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Bo young
authors.initials: By
authors.lastname: Rho
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Lee
authors.forename: Jae Myun
authors.initials: JM
authors.lastname: Lee
authors.forename: Se Jong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jeon Han
authors.initials: JH
authors.lastname: Park
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D000071636:Protein Phosphatase 2C; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C