Specific binding of the ETS-domain protein to the interferon-stimulated response element

J Interferon Cytokine Res. 1997 Jan;17(1):1-10. doi: 10.1089/jir.1997.17.1.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics*
  • Base Sequence
  • Cells, Cultured
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Enzymologic / drug effects
  • HeLa Cells
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology*
  • Interferon-gamma / pharmacology*
  • Molecular Sequence Data
  • Multigene Family
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary*
  • Proto-Oncogene Mas
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ets
  • Recombinant Proteins
  • Stimulation, Chemical
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics


  • DNA-Binding Proteins
  • ETS1 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Recombinant Proteins
  • Transcription Factors
  • Interferon-gamma
  • 2',5'-Oligoadenylate Synthetase