title: Specific binding of the ETS-domain protein to the interferon-stimulated response element.
abstract: Interferon (IFN) activation of genes bearing an IFN-stimulated response element (ISRE) is regulated through binding of IFN-stimulated gene factors (ISGF) to the ISRE found in many IFN-stimulated genes. Using a multimerized human 2-5A synthetase ISRE as probe, we screened lambda gt11 expression libraries for cDNA encoding ISRE-binding activity and isolated a clone for murine proto-oncogene ets-1. The Ets-1 protein binds to the 2-5A synthetase ISRE at a site that also binds ISGF3, a multicomponent factor whose ISRE binding correlates with IFN-induced activation of transcription from ISRE-containing promoters. IFN-induced ISGF3 complex formation on the ISRE can be inhibited by specific Ets-1 antibody. Coexpression of Ets-1 represses ISRE-dependent reporter activity, suggesting that one or more members of the Ets protein family may negatively regulate transcriptional activity mediated by the 2-5A synthetase ISRE.
authors.affiliation: Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada.
authors.forename: M N
authors.initials: MN
authors.lastname: Rutherford
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: S J
authors.initials: SJ
authors.lastname: Haque
authors.forename: J
authors.initials: J
authors.lastname: Ghysdael
authors.forename: B R
authors.initials: BR
authors.lastname: Williams
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D014157:Transcription Factors; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase