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Tumor Necrosis Factor-Alpha Activation of the IL-2 Receptor-Alpha Gene Involves the Induction of Kappa B-specific DNA Binding Proteins

Tumor Necrosis Factor-Alpha Activation of the IL-2 Receptor-Alpha Gene Involves the Induction of Kappa B-specific DNA Binding Proteins

J W Lowenthal, D W Ballard, H Bogerd, E Böhnlein, W C Greene

J Immunol. 1989 May 1;142(9):3121-8.

PMID: 2785134

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248883	sTNF-receptor Type I human			Price

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