The hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathway.

2.50
Hdl Handle:
http://hdl.handle.net/2436/7705
Title:
The hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathway.
Authors:
Lara-Pezzi, Enrique; Armesilla, Angel Luis; Majano, Pedro L.; Redondo, Juan Miguel; López-Cabrera, Manuel
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.
Citation:
The EMBO Journal, 17(23): 7066-7077
Publisher:
Nature Publishing Group
Issue Date:
1998
URI:
http://hdl.handle.net/2436/7705
DOI:
10.1093/emboj/17.23.7066
PubMed ID:
9843511
Additional Links:
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1171054&blobtype=pdf
Type:
Article
Language:
en
ISSN:
0261-4189
Appears in Collections:
Molecular Pharmacology Research Group

Full metadata record

DC FieldValue Language
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): 7066-7077en
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.en
dc.format.extent515930 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1171054&blobtype=pdfen
dc.subjectX geneen
dc.subjectHepatitis B virusen
dc.subjectTNF-alphaen
dc.subjectTumor Necrosis Factor-alphaen
dc.titleThe hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathway.en
dc.typeArticleen
dc.format.digYES-
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