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.
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.
Lowenthal
J W
JW
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Ballard
D W
DW
Böhnlein
E
E
Greene
W C
WC
D001483:Base Sequence; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005796:Genes / Q000187:drug effects*; D005803:Genes, Immunoglobulin; D015497:HIV-1 / Q000276:immunology*; D015486:HTLV-I Antigens / Q000276:immunology*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007376:Interleukin-2 / Q000276:immunology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D015486:HTLV-I Antigens; D007145:Immunoglobulin kappa-Chains; D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate