Inhibition of the RelA(p65) NF-kappa B subunit by Egr-1

Induction of transcription from the human immunodeficiency virus 1 long ter minal repeat by the RelA (p65) NF-kappa B subunit has been shown to be depe ndent upon an interaction with the zinc finger DNA-binding domain of Sp1. I t was unknown, however, whether NF-kappa B could also interact with other z inc finger-containing transcription factors. In this study we demonstrate t hat the early growth response transcription factor Egr-1, whose DNA-binding domain shares a high degree of homology with that of Sp1, can also interac t with RelA in vitro and regulate NF-kappa B transcriptional activity in vi vo. Similar to the interaction with Sp1, the Rel homology domain of RelA in teracts with the zinc finger domain of Egr-1, Surprisingly, and in contrast to Sp1, Egr-1 specifically represses RelA transcriptional activity through its zinc finger domain. Moreover, the interaction between RelA and the Egr -1 zinc fingers is mutually exclusive with DNA binding suggesting a model i n which Egr-1 directly sequesters NF-kappa B from its target promoters. Bec ause Egr-1 is induced by many of the same stimuli that activate NF-kappa B, this novel transcriptional regulatory mechanism has many implications for the involvement of both factors in cellular processes such as apoptosis and the response to stress and infection.