Tumor necrosis factor-alpha activation of the IL-2 receptor-alpha gene involves the induction of kappa B-specific DNA binding proteins

J Immunol. 1989 May 1;142(9):3121-8.

Abstract

TNF-alpha induces the expression of IL-2R and promotes the proliferation and differentiation of T and B cells. In this report, we have studied the biochemical basis for TNF-alpha activation of the IL-2R alpha (Tac, p55) gene. Transfection of human T cell lines with selectively mutated forms of the IL-2R alpha promoter revealed that a kappa B element (nucleotides -267 to -256), as well as 5' flanking sequences (nucleotides -281 to -271) are required for TNF-alpha induction of this transcriptional unit. DNA binding studies demonstrated that this IL-2R alpha kappa B control element is specifically bound by a set of TNF-alpha inducible T cell nuclear proteins of relative Mr 80 to 90, 50 to 55, and 38 to 42 kDa. This protein recognition site from the IL-2R alpha promoter, as well as related kappa B motifs from the long terminal repeat of the type I human immunodeficiency virus, proved sufficient to impart TNF-alpha inducibility to an unresponsive heterologous promoter. These findings suggest that TNF-alpha-stimulated expression of the IL-2R alpha gene involves the induction of specific DNA binding proteins that in turn interact with a kappa B-like promoter element and facilitate activation of this transcription unit.

MeSH terms

  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / radiation effects
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / radiation effects
  • Humans
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / metabolism
  • Nucleotide Mapping
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / radiation effects
  • Receptors, Interleukin-2 / genetics*
  • Receptors, Interleukin-2 / radiation effects
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcription Factors / radiation effects
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Ultraviolet Rays

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Receptors, Interleukin-2
  • Transcription Factors
  • Tumor Necrosis Factor-alpha