Mechanisms by which IκB proteins control NF-κB activity
Mechanisms by which IκB proteins control NF-κB activity
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DOI：
10.1073/pnas.96.1.49
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发表时间：
1999-01-05
影响因子：
11.1
通讯作者：
Thanos, D
中科院分区：
文献类型：
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作者：
Simeonidis, S;Stauber, D;Thanos, D
转录因子NF-kappa B的生物活性由三种I kappa B蛋白差异控制，I kappa B α， I kappa B β和I kappa B epsilon。我们通过构建ikappa B杂交体，研究了ikappa B蛋白差异抑制强度的分子基础，发现ikappa Ba的第一个锚蛋白重复序列是其强抑制作用的原因。在第一个锚蛋白重复序列中，在强I κ B α和弱I κ B β抑制剂之间交换一个假定的β转，可以改变它们对NF-kappa B的体内抑制活性。在I κ B α和I κ B β中，这种p转与NF-kappa B在质量上的不同接触，决定了I κ B将NF-kappa B隔离到细胞质上的效率，从而解释了它们对基因活性的不同影响。
The biological activity of the transcription factor NF-kappa B is differentially controlled by three I kappa B proteins, I kappa B alpha, I kappa B beta, and I kappa B epsilon. We have examined the molecular basis for the differential inhibitory strengths of I kappa B proteins by constructing hybrid I kappa Bs and found that the first ankyrin repeat of I kappa Ba is responsible for its strong inhibitory effect. Swapping a putative beta-turn within the first ankyrin repeat between the strong I kappa B alpha and the weak I kappa B beta inhibitors switches their in vivo inhibitory activity on NF-kappa B. The qualitatively distinct contacts made by this p-turn in I kappa B alpha and I kappa B beta with NF-kappa B determine the efficiency by which I kappa Bs sequester NF-kappa B to the cytoplasm, thus explaining their distinct effects on gene activity.