Critical role of a common transcription factor, IRF-1, in the regulation of IFN-beta and IFN-inducible genes

EMBO J. 1992 Jan;11(1):185-93.

Abstract

Interferon regulatory factor 1 (IRF-1) is a protein that binds to cis-elements within the promoter of interferon (IFN)-beta and some IFN-inducible genes. We used a human fibroblast line, GM-637, to generate stable transfectants constitutively expressing IRF-1 mRNA in either the sense or antisense orientation. Upon induction with poly-(I).poly(C) or Newcastle disease virus, cells expressing sense IRF-1 mRNA produced significantly higher levels of IFN-beta mRNA and protein than control cells, whereas cells expressing antisense IRF-1 mRNA produced little or no IFN-beta mRNA and protein. Furthermore, clear differences were seen among the transfectants in the level of expression of two IFN-induced genes (2'-5'-oligoadenylate synthetase and class I HLA). Our data show that IRF-1 is essential for the induced expression of the IFN-beta gene. The results also indicate an important role of IRF-1 in the expression of IFN-inducible genes and suggest a role for IRF-1 in many other cytokine actions.

Publication types

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

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Cell Line, Transformed
  • DNA-Binding Proteins / genetics*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Interferon Regulatory Factor-1
  • Interferons / pharmacology*
  • Major Histocompatibility Complex / genetics
  • Phosphoproteins / genetics*
  • RNA
  • RNA, Antisense
  • Skin / cytology
  • Transcription Factors / genetics*
  • Transfection

Substances

  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Phosphoproteins
  • RNA, Antisense
  • RNA, recombinant
  • Transcription Factors
  • RNA
  • Interferons
  • 2',5'-Oligoadenylate Synthetase