NFkappaB activation is required for interferon regulatory factor-1-mediated interferon beta induction

Eur J Biochem. 1999 Apr;261(2):546-54. doi: 10.1046/j.1432-1327.1999.00308.x.


The interferon regulatory factor 1 (IRF-1) acts as a transcriptional inducer of the interferon beta (IFN-beta) gene and interferon-stimulated genes. Here we report that IRF-1-mediated IFN-beta induction depends on NFkappaB activity. IRF-1 by itself initiates NFkappaB activation by inducing a reduction in cellular MAD3/IkappaBalpha, an inhibitor of NFkappaB. After nuclear translocation, NFkappaB synergizes with IRF-1 on the cis-elements positive regulatory domain (PRD)II and PRDI/III to induce transcription of the IFN-beta gene. In contrast with IFN-beta transcription induced by dsRNA or virus, c-Jun/ATF-2 binding to PRDIV is not involved. Recombinant MAD3/IkappaBalpha is phosphorylated in vitro by extracts from IRF-1-expressing cells. IRF-1-dependent MAD3/IkappaBalpha degradation is not detectable in cells expressing a dominant negative mutant of the protein kinase PKR, suggesting that PKR mediates MAD3/IkappaBalpha degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / genetics
  • Genes, Reporter / genetics
  • I-kappa B Proteins*
  • Interferon Regulatory Factor-1
  • Interferon-beta / genetics*
  • Microscopy, Fluorescence
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Nuclear Proteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Promoter Regions, Genetic / genetics
  • Recombinant Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics
  • Transfection
  • eIF-2 Kinase / metabolism


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Interferon Regulatory Factor-1
  • NF-kappa B
  • Nuclear Proteins
  • Phosphoproteins
  • Recombinant Proteins
  • NF-KappaB Inhibitor alpha
  • Interferon-beta
  • eIF-2 Kinase