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dc.contributor.authorLara-Pezzi, Enrique
dc.contributor.authorArmesilla, Angel Luis
dc.contributor.authorMajano, Pedro L.
dc.contributor.authorRedondo, Juan Miguel
dc.contributor.authorLópez-Cabrera, Manuel
dc.date.accessioned2007-01-23T17:04:32Z
dc.date.available2007-01-23T17:04:32Z
dc.date.issued1998
dc.identifier.citationThe EMBO Journal, 17(23): 7066-7077
dc.identifier.issn0261-4189
dc.identifier.pmid9843511
dc.identifier.doi10.1093/emboj/17.23.7066
dc.identifier.urihttp://hdl.handle.net/2436/7705
dc.description.abstractThe 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.extent515930 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.urlhttp://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1171054&blobtype=pdf
dc.subjectX gene
dc.subjectHepatitis B virus
dc.subjectTNF-alpha
dc.subjectTumor Necrosis Factor-alpha
dc.titleThe hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathway.
dc.typeJournal article
dc.format.digYES
refterms.dateFOA2018-08-20T14:24:07Z
html.description.abstractThe 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.


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