Inhibition of the RelA(p65) NF-kappaB subunit by Egr-1.
Induction of transcription from the human immunodeficiency virus 1 long terminal repeat by the RelA (p65) NF-kappaB subunit has been shown to be dependent upon an interaction with the zinc finger DNA-binding domain of Sp1. It was unknown, however, whether NF-kappaB could also interact with other zinc finger-containing transcription factors. In this study we demonstrate that the early growth response transcription factor Egr-1, whose DNA-binding domain shares a high degree of homology with that of Sp1, can also interact with RelA in vitro and regulate NF-kappaB transcriptional activity in vivo. Similar to the interaction with Sp1, the Rel homology domain of RelA interacts 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 in which Egr-1 directly sequesters NF-kappaB from its target promoters. Because Egr-1 is induced by many of the same stimuli that activate NF-kappaB, 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.
Chapman
N R
NR
Department of Biochemistry, Division of Gene Expression and Regulation, MSI/WTB Complex, Dow Street, University of Dundee, Dundee, DD1 5EH Scotland, United Kingdom.
Perkins
N D
ND
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D051766:Early Growth Response Protein 1; D006801:Humans; D017874:Immediate-Early Proteins; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011401:Promoter Regions, Genetic; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014157:Transcription Factors