Léveillard T, Verma I M
Molecular Biology and Viroiogy Laboratory, Salk Institute, San Diego, CA 92186-5800.
Gene Expr. 1993;3(2):135-50.
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.
κB位点结合蛋白的rel/NF-κB/背侧家族的活性受IκB蛋白调控。锚蛋白重复基序鉴定出了IκB家族成员，其中包括IκBα（pp40/MAD-3）、IκBγ和bcl3，它们直接与κB位点结合蛋白相关，导致rel、p50或p65二聚体的特异性DNA结合受到抑制。我们报道，含有八个锚蛋白重复序列的IκBγ介导了对（p50）2-DNA复合物的可逆抑制，但不能取代预先形成的DNA-蛋白质复合物。另一方面，IκBα和bcl3可以取代预先形成的DNA-蛋白质复合物。IκBα特异性取代（p65）2或p50/p65-DNA复合物，但除了锚蛋白重复结构域外还需要C末端的37个氨基酸。人bcl3蛋白特异性取代（p50）2-DNA复合物。由于IκBα和bcl3分别可以取代预先形成的（p65）2或（p50）2-DNA复合物，我们提出它们可以作为NF-κB诱导的基因表达的阻遏物或抗阻遏物。
