A mutant Rel-homology domain promotes transcription by p50/NFkappaB1.
Previous studies showed that the binding of p50/NFkappaB1 to particular kappaB DNA sites altered its conformation in a way that correlated with transcriptional activation. Here, we investigated the effects of protein-protein interactions on the transcriptional activity of p50. We show that the association of p50 with a mutant Rel-homology domain (RHD) defective for DNA binding led to synergistic activation of kappaB site-dependent transcription, whereas neither protein alone had any effect. Partial proteolytic analysis showed that the conformation of p50 in these complexes differed from that in wild-type c-Rel-RHD/p50 complexes, and correlated with activated transcription. These results suggest that the Rel-homology domain can act as an allosteric effector to promote transcription by p50/NFkappaB1 and that the configuration of p50 is important for its activity. This also suggests that Rel proteins can promote transcription by other Rel-family members without binding to their DNA recognition site. These studies emphasize the important role of protein-protein interactions in Rel and NFkappaB-mediated transcription.
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Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854-5638, USA.
Gélinas
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D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors