Diverse molecular mechanisms of inhibition of NF-kappa B/DNA binding complexes by I kappa B proteins.
The activity of the rel/NF-kappa B/dorsal family of kappa B site binding proteins is regulated by I kappa B proteins. The ankyrin repeat motif identified I kappa B family members, which include I kappa B alpha (pp40/MAD-3), I kappa B gamma, and bcl3, directly associated with kappa B site binding proteins, resulting in specific DNA-binding inhibition of rel, p50, or p65 dimers. We report that I kappa B gamma, containing eight ankyrin repeats, mediates a reversible inhibition of (p50)2-DNA complex but cannot displace preformed DNA-protein complexes. I kappa B alpha and bcl3, on the other hand, can displace preformed DNA-protein complexes. I kappa B alpha specifically displaces (p65)2 or p50/p65-DNA complexes but requires the C-terminal 37 amino acids in addition to the ankyrin repeat domain. Human bcl3 protein specifically displaces (p50)2-DNA complexes. Because I kappa B alpha and bcl3 can displace preformed (p65)2 or (p50)2-DNA complexes, respectively, we propose that they can act as repressors or antirepressors of NF-kappa B-induced gene expression.
Léveillard
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Molecular Biology and Viroiogy Laboratory, Salk Institute, San Diego, CA 92186-5800.
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D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000235:genetics; D000081242:B-Cell Lymphoma 3 Protein; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction; D051841:Transcription Factor RelB; D014157:Transcription Factors
D017487:Ankyrins; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; D004247:DNA