Regulation of the IL-2 receptor alpha-gene. Interaction of a kappa B binding protein with cell-specific transcription factors.
The IL-2R alpha enhancer contains an 11 bp sequence that resembles kappa B, a regulatory element associated with several genes, including Ig kappa-L chain and human immunodeficiency virus. Although nuclear factor of the kappa-enhancer in B cells (NF-kappa B) binding is activated by PMA, TNF-alpha, and IL-1, activation of the IL-2R alpha enhancer does not consistently correlate with NF-kappa B induction. In this report, we show that TNF-alpha activates NF-kappa B and the human immunodeficiency virus enhancer in the Jurkat T leukemia but does not stimulate the IL-2R alpha enhancer. In contrast, this cytokine, and IL-1, increased IL-2R alpha gene expression in YT-1 cells. Comparing YT-1 and Jurkat T leukemias, we find that the IL-2R kappa B site is required for TNF-alpha and IL-1 stimulation in YT-1 cells, but that plasmids containing this site linked to a heterologous promoter do not respond to these cytokines. These data suggest that upstream regulatory elements in addition to IL-2R kappa B are needed to mediate this cytokine effect. TNF-alpha also synergized with PMA and other cytokines in the stimulation of the IL-2R alpha enhancer in YT-1. Because these effects are not observed in Jurkat cells, the function of the IL-2R kappa B site is cell-specific and likely mediated by different associated transcription factors present in each cell type.
Freimuth
W W
WW
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Depper
J M
JM
Nabel
G J
GJ
D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate