The interaction of hepatitis B virus X protein and protein phosphatase type 2 Calpha and its effect on IL-6.
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.
Kim
Ji Su
JS
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.
Rho
Bo young
By
Lee
Tae Ho
TH
Lee
Jae Myun
JM
Kim
Se Jong
SJ
Park
Jeon Han
JH
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*
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