Discrimination between RelA and RelB transcriptional regulation by a dominant negative mutant of IκBα

Abstract

RelA and RelB belong to the nuclear factor-κB (NF-κB-Rel) transcription factor family. Both proteins are structurally and functionally related, but their intracellular and tissue distributions are different. In resting cells, RelB is found mostly in the nucleus, whereas RelA is sequestered in the cytosol by protein inhibitors, among which Iκ-Bα is the dominant form in lymphocytes. Upon cellular activation IκBα is proteolyzed, allowing RelA dimers to enter the nucleus and activate target genes. To study the selectivity of gene regulation by RelA and RelB, we generated T cell lines stably expressing a dominant negative mutant of IκBα. We show that selective inhibition of RelA-NF-κB decreased induction of NFKB1, interleukin-2, and interleukin-2Rα genes but not c-myc. Transcription driven by the IκBα promoter was blocked by the transgenic IκBα; however, wild type IκBα was expressed in the transgenic cell clones but with much slower kinetics than that in control cells. Wild type IκBα expression was concomitant with ReLB up-regulation, suggesting that RelB could be involved in transcription of IκBα through binding to an alternative site. These results indicate that RelB and RelA have both distinct and overlapping effects on gene expression.