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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2',5'-Oligoadenylate Synthetase / genetics*
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Base Sequence
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Cells, Cultured
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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Gene Expression Regulation, Enzymologic / drug effects
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HeLa Cells
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Humans
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Interferon alpha-2
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Interferon-alpha / pharmacology*
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Interferon-gamma / pharmacology*
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Molecular Sequence Data
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Multigene Family
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Promoter Regions, Genetic
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Protein Binding
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Protein Structure, Tertiary*
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Proto-Oncogene Mas
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins / chemistry*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-ets
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Recombinant Proteins
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Stimulation, Chemical
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Transcription Factors / chemistry*
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Transcription Factors / genetics
Substances
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DNA-Binding Proteins
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ETS1 protein, human
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Interferon alpha-2
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Interferon-alpha
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MAS1 protein, human
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Proto-Oncogene Mas
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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Recombinant Proteins
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Transcription Factors
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Interferon-gamma
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2',5'-Oligoadenylate Synthetase