Promoter of the human NF-kappa B p50/p105 gene. Regulation by NF-kappa B subunits and by c-REL.

Abstract

NF-kappa B is a transcription factor involved in the regulation of numerous genes encoding proteins involved in immune function, in inflammation or in cellular growth control. NF-kappa B is typically characterized as a heterodimer of a 50-kDa subunit (p50) and a 65-kDa (p65) subunit. Interestingly, the p50 subunit is derived by processing of a 105-kDa precursor. Induction of NF-kappa B DNA-binding activity involves both the release of cytoplasmically stored factor from its inhibitor known as I kappa B and the induction of NF-kappa B gene expression. We report here the cloning and functional analysis of the promoter of the p50/p105 NF-kappa B gene. Our data suggest the existence of multiple transcription initiation sites for this gene in the B cell line Raji, Jurkat T cells, and HeLa cells. The promoter is constitutively active in these cells and is inducible by phorbol ester and mitogen stimulation of Jurkat T cells. Expression of I kappa B inhibits this inducible activation of the p50/p105 promoter. Furthermore, we have shown that co-transfection of a p50/p105 promoter-reporter plasmid with expression vectors encoding the p50 or p65 subunits of NF-kappa B or c-Rel results in stimulation of gene expression. Supportive of the transfection data, we have identified a DNA-binding site for NF-kappa B in the promoter of the p50/p105 gene that is responsive only to a combination of p50 and p65. The data demonstrate that the p50/p105 NF-kappa B gene is regulated by members of the NF-kappa B/Rel family and likely by other important transcription factors.