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dc.contributor.authorWong, LH
dc.contributor.authorSim, H
dc.contributor.authorChatterjee-Kishore, M
dc.contributor.authorHatzinisiriou, I
dc.contributor.authorDevenish, RJ
dc.contributor.authorStark, G
dc.contributor.authorRalph, SJ
dc.contributor.editorHerbert Tabor
dc.date.accessioned2017-05-03T14:15:00Z
dc.date.available2017-05-03T14:15:00Z
dc.date.issued2002
dc.date.modified2009-04-23T08:00:40Z
dc.identifier.issn0021-9258
dc.identifier.doi10.1074/jbc.M111302200
dc.identifier.urihttp://hdl.handle.net/10072/22668
dc.description.abstractThe transcription factor STAT1 plays a pivotal role in signal transduction of type I and II interferons (IFNs). STAT1 activation leads to changes in expression of key regulatory genes encoding caspases and cell cycle inhibitors. Deficient STAT1 expression in human cancer cells and virally mediated inhibition of STAT1 function have been associated with cellular resistance to IFNs and mycobacterial infection in humans. Thus, given the relative importance of STAT1, we isolated and characterized a human STAT1 intronic enhancer region displaying IFN-regulated activity. Functional analyses by transient expression identified a repressor region and type I and II IFN-inducible elements within the STAT1 enhancer sequence. A candidate IRF-E/GAS/IRF-E (IGI) sequence containing GAAANN nucleotide repeats was shown by gel shift assay to bind to IFN regulatory factor-1 (IRF-1), but not to IFN-stimulated gene factor-3 (ISGF-3) or STAT1-3. An additional larger IGI-binding complex containing IRF-1 was identified. Mutation of the GAAANN repeats within the IGI DNA element eliminated IRF-1 binding and the IFN-regulated activity of the STAT1 intronic enhancer region. Transfection of the IFN-resistant MM96 cell line to express increased levels of IRF-1 protein also elevated STAT1, STAT2, and p48/IRF-9 expression and enhanced cellular responsiveness to IFN-. Reciprocating regulation between IRF-1 and STAT1 genes and encoded proteins indicates that an intracellular amplifier circuit exists controlling cellular responsiveness to the IFNs.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_AU
dc.publisherThe American Society for Biochemistry and Molecular Biology
dc.publisher.placeMaryland, USA
dc.relation.ispartofpagefrom19408
dc.relation.ispartofpageto19417
dc.relation.ispartofissue22
dc.relation.ispartofjournalJournal of Biological Chemistry
dc.relation.ispartofvolume277
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchChemical Sciences
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode11
dc.subject.fieldofresearchcode03
dc.titleIsolation and characterization of a human STAT1 gene regulatory element: Inducibility by interferon (IFN) types I and II and role of IFN regulatory factor-1
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2002
gro.hasfulltextNo Full Text
gro.griffith.authorRalph, Stephen J.


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