The hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathway.
dc.contributor.author | Lara-Pezzi, Enrique | |
dc.contributor.author | Armesilla, Angel | |
dc.contributor.author | Majano, Pedro L. | |
dc.contributor.author | Redondo, Juan Miguel | |
dc.contributor.author | López-Cabrera, Manuel | |
dc.date.accessioned | 2007-01-23T17:04:32Z | |
dc.date.available | 2007-01-23T17:04:32Z | |
dc.date.issued | 1998-12-01 | |
dc.identifier.citation | The EMBO Journal, 17(23): 7066-7077 | |
dc.identifier.issn | 0261-4189 | |
dc.identifier.pmid | 9843511 | |
dc.identifier.doi | 10.1093/emboj/17.23.7066 | |
dc.identifier.uri | http://hdl.handle.net/2436/7705 | |
dc.description.abstract | The X gene product of the human hepatitis B virus (HBx) is a transcriptional activator of various viral and cellular genes. We recently have determined that the production of tumor necrosis factor-alpha (TNF-alpha) by HBV-infected hepatocytes is transcriptionally up-regulated by HBx, involving nuclear factor of activated T cells (NF-AT)-dependent activation of the TNF-alpha gene promoter. Here we show that HBx activates NF-AT by a cyclosporin A-sensitive mechanism involving dephosphorylation and nuclear translocation of the transcription factor. Luciferase gene expression assays demonstrated that HBx transactivates transcription through NF-AT-binding sites and activates a Gal4-NF-AT chimeric protein. DNA-protein interaction assays revealed that HBx induces the formation of NF-AT-containing DNA-binding complexes. Immunofluorescence analysis demonstrated that HBx induces the nuclear translocation of NF-AT, which can be blocked by the immunosuppressive drug cyclosporin A. Furthermore, immunoblot analysis showed that the HBx-induced activation and translocation of NF-AT are associated with its dephosphorylation. Thus, HBx may play a relevant role in the intrahepatic inflammatory processes by inducing locally the expression of cytokines that are regulated by NF-AT. | |
dc.format.extent | 515930 bytes | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.publisher | Nature Publishing Group | |
dc.relation.url | http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1171054&blobtype=pdf | |
dc.subject | X gene | |
dc.subject | Hepatitis B virus | |
dc.subject | TNF-alpha | |
dc.subject | Tumor Necrosis Factor-alpha | |
dc.title | The hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathway. | |
dc.type | Journal article | |
dc.format.dig | YES | |
refterms.dateFOA | 2018-08-20T14:24:07Z | |
html.description.abstract | The X gene product of the human hepatitis B virus (HBx) is a transcriptional activator of various viral and cellular genes. We recently have determined that the production of tumor necrosis factor-alpha (TNF-alpha) by HBV-infected hepatocytes is transcriptionally up-regulated by HBx, involving nuclear factor of activated T cells (NF-AT)-dependent activation of the TNF-alpha gene promoter. Here we show that HBx activates NF-AT by a cyclosporin A-sensitive mechanism involving dephosphorylation and nuclear translocation of the transcription factor. Luciferase gene expression assays demonstrated that HBx transactivates transcription through NF-AT-binding sites and activates a Gal4-NF-AT chimeric protein. DNA-protein interaction assays revealed that HBx induces the formation of NF-AT-containing DNA-binding complexes. Immunofluorescence analysis demonstrated that HBx induces the nuclear translocation of NF-AT, which can be blocked by the immunosuppressive drug cyclosporin A. Furthermore, immunoblot analysis showed that the HBx-induced activation and translocation of NF-AT are associated with its dephosphorylation. Thus, HBx may play a relevant role in the intrahepatic inflammatory processes by inducing locally the expression of cytokines that are regulated by NF-AT. |