IκB蛋白调控核因子κB（NF-κB）活性的机制。
Mechanisms by which IkappaB proteins control NF-kappaB activity.
作者信息
Simeonidis S, Stauber D, Chen G, Hendrickson W A, Thanos D
机构信息
Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):49-54. doi: 10.1073/pnas.96.1.49.
Abstract
The biological activity of the transcription factor NF-kappaB is differentially controlled by three IkappaB proteins, Ikappa Balpha, Ikappa Bbeta, and Ikappa Bepsilon. We have examined the molecular basis for the differential inhibitory strengths of IkappaB proteins by constructing hybrid IkappaBs and found that the first ankyrin repeat of Ikappa Balpha is responsible for its strong inhibitory effect. Swapping a putative beta-turn within the first ankyrin repeat between the strong Ikappa Balpha and the weak IkappaBbeta inhibitors switches their in vivo inhibitory activity on NF-kappaB. The qualitatively distinct contacts made by this beta-turn in Ikappa Balpha and Ikappa Bbeta with NF-kappaB determine the efficiency by which IkappaBs sequester NF-kappaB to the cytoplasm, thus explaining their distinct effects on gene activity.
摘要
转录因子NF-κB的生物活性受到三种IκB蛋白（IκBα、IκBβ和IκBε）的差异调控。我们通过构建杂交IκB蛋白来研究IκB蛋白差异抑制强度的分子基础，发现IκBα的第一个锚蛋白重复序列是其强大抑制作用的原因。在强抑制性的IκBα和弱抑制性的IκBβ抑制剂之间交换第一个锚蛋白重复序列内的一个假定β转角，会改变它们在体内对NF-κB的抑制活性。IκBα和IκBβ中这个β转角与NF-κB形成的性质不同的接触，决定了IκB蛋白将NF-κB隔离到细胞质中的效率，从而解释了它们对基因活性的不同影响。
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