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Vol. 273, Issue 1, 592-599, January 2, 1998

Discrimination between RelA and RelB Transcriptional Regulation by a Dominant Negative Mutant of Ikappa Balpha

Valérie Ferreira, Nadine Tarantino, and Marie Körner

From the Laboratoire d'Immunologie Cellulaire, CNRS URA 625, Bat. CERVI, Hôpital de la Pitié Salpêtrière, 83, Bd. de l'Hôpital, 75013 Paris, France

RelA and RelB belong to the nuclear factor-kappa B (NF-kappa B-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 Ikappa Balpha is the dominant form in lymphocytes. Upon cellular activation Ikappa Balpha 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 Ikappa Balpha . We show that selective inhibition of RelA-NF-kappa B decreased induction of NFKB1, interleukin-2, and interleukin-2Ralpha genes but not c-myc. Transcription driven by the Ikappa Balpha promoter was blocked by the transgenic Ikappa Balpha ; however, wild type Ikappa Balpha was expressed in the transgenic cell clones but with much slower kinetics than that in control cells. Wild type Ikappa Balpha expression was concomitant with RelB up-regulation, suggesting that RelB could be involved in transcription of Ikappa Balpha through binding to an alternative site. These results indicate that RelB and RelA have both distinct and overlapping effects on gene expression.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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