Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes

Proc Natl Acad Sci U S A. 1989 Apr;86(7):2331-5. doi: 10.1073/pnas.86.7.2331.


We have investigated the biochemical basis for the activation of interleukin 2 receptor alpha-subunit (IL-2R alpha) gene expression in primary human T lymphocytes by a cytokine (tumor necrosis factor alpha), a T-cell mitogen (phorbol 12-myristate 13-acetate), and the transactivator protein (Tax) from the type I human T-cell leukemia virus. Using in vivo transfection techniques specificially designed for these primary T cells in conjunction with in vitro gel retardation and DNA footprinting assays, we found that activation of the IL-2R alpha promoter by each of these agents involves the induction of nuclear proteins that specifically interact with a kappa B-like enhancer element (i.e., an element resembling the immunoglobulin kappa-chain enhancer sequence recognized by transcription factor NF-kappa B). DNA-protein crosslinking studies revealed that primary T cells express at least three different inducible DNA-binding proteins (50-55, 70-75, and 80-90 kDa) that specifically interact with this IL-2R alpha kappa B element.

MeSH terms

  • Base Sequence
  • Chromosome Deletion
  • DNA-Binding Proteins / biosynthesis*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation*
  • Genes / drug effects*
  • Genes, Immunoglobulin
  • HIV-1 / immunology*
  • HTLV-I Antigens / immunology*
  • Humans
  • Immunoglobulin kappa-Chains / genetics*
  • Interleukin-2 / immunology*
  • Macromolecular Substances
  • Molecular Sequence Data
  • Mutation
  • Receptors, Interleukin-2 / genetics*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Trans-Activators
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology*


  • DNA-Binding Proteins
  • HTLV-I Antigens
  • Immunoglobulin kappa-Chains
  • Interleukin-2
  • Macromolecular Substances
  • Receptors, Interleukin-2
  • Trans-Activators
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Tetradecanoylphorbol Acetate