Regulation of the IL-2 receptor α-gene. Interaction of a κB binding protein with cell-specific transcription factors

W. W. Freimuth, J. M. Depper, G. J. Nabel

Research output: Contribution to journalArticle

Abstract

The IL-2Rα enhancer contains an 11 bp sequence that resembles κB, a regulatory element associated with several genes, including Ig κ-L chain and human immunodeficiency virus. Although nuclear factor of the κ-enhancer in B cells (NF-κB) binding is activated by PMA, TNF-α, and IL-1, activation of the IL-2Rα enhancer does not consistently correlate with NF-κB induction. In this report, we show that TNF-α activates NF-κB and the human immunodeficiency virus enhancer in the Jurkat T leukemia but does not stimulate the IL-2Rα enhancer. In contrast, this cytokine, and IL-1, increased IL-2Rα gene expression in YT-1 cells. Comparing YT-1 and Jurkat T leukemias, we find that the IL-2R κB site is required for TNF-α 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 κB are needed to mediate this cytokine effect. TNF-α also synergized with PMA and other cytokines in the stimulation of the IL-2Rα enhancer in YT-1. Because these effects are not observed in Jurkat cells, the function of the IL-2R κB site is cell-specific and likely mediated by different associated transcription factors present in each cell type.

Original languageEnglish (US)
Pages (from-to)3064-3068
Number of pages5
JournalJournal of Immunology
Volume143
Issue number9
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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