Tumor necrosis factor-alpha activation of the IL-2 receptor-alpha gene involves the induction of kappa B-specific DNA binding proteins.
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.
Lowenthal
J W
JW
Howard Hughes Medical Institute, Department of Medicine, Durham, North Carolina 27710.
Ballard
D W
DW
Bogerd
H
H
Böhnlein
E
E
Greene
W C
WC
D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism; D009710:Nucleotide Mapping; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000528:radiation effects; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000528:radiation effects; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha