DISCRIMINATION BETWEEN RELA AND RELB TRANSCRIPTIONAL REGULATION BY A DOMINANT-NEGATIVE MUTANT OF I-KAPPA-B-ALPHA

RelA and RelB belong to the nuclear factor-kappa B (NF-kappa B-Rel) tr anscription factor family. Both proteins are structurally and function ally related, but their intracellular and tissue distributions are dif ferent. In resting cells, RelB is found mostly in the nucleus, whereas RelA is sequestered in the cytosol by protein inhibitors, among which I kappa B alpha is the dominant form in lymphocytes. Upon cellular ac tivation I kappa B alpha is proteolyzed, allowing RelA dimers to enter the nucleus and activate target genes. To study the selectivity of ge ne regulation by RelA and RelB, we generated T cell lines stably expre ssing a dominant negative mutant of I kappa B alpha. We show that sele ctive inhibition of RelA-NF-kappa B decreased induction of NPKB1, inte rleukin-2, and interleukin-2R alpha genes but not c-myc. Transcription driven by the I kappa B alpha promoter was blocked by the transgenic I kappa B alpha; however, wild type I kappa B alpha was expressed in t he transgenic cell clones but with much slower kinetics than that in c ontrol cells. Wild type I kappa B alpha expression was concomitant wit h RelB up-regulation, suggesting that RelB could be involved in transc ription of I kappa B alpha through binding to an alternative site. The se results indicate that RelB and RelA have both distinct and overlapp ing effects on gene expression.