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.