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Kinetic enhancement of NF-κB-DNA dissociation by IκBα

机译:IκBα促进NF-κB-DNA解离的动力学

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摘要

A hallmark of the NF-κB transcription response to inflammatory cytokines is the remarkably rapid rate of robust activation and subsequent signal repression. Although the rapidity of postinduc-tion repression is explained partly by the fact that the gene for IκBα is strongly induced by NF-κB, the newly synthesized IκBα: still must enter the nucleus and compete for binding to NF-κB with the very large number of κB sites in the DNA. We present results from real-time binding kinetic experiments, demonstrating that IκBα increases the dissociation rate of NF-κB from the DNA in a highly efficient kinetic process. Analysis of various IκB mutant proteins shows that this process requires the C-terminal PEST sequence and the weakly folded fifth and sixth ankyrin repeats of IκBα. Muta-tional stabilization of these repeats reduces the efficiency with which IκBα enhances the dissociation rate.
机译:对炎性细胞因子的NF-κB转录反应的标志是鲁棒激活和随后信号抑制的显着快速速率。尽管诱导后抑制的快速性部分是由于NF-κB强烈诱导了IκBα基因的事实,但新合成的IκBα:仍必须进入细胞核并竞争与NF-κB的大量结合DNA中的κB位点。我们目前的实时结合动力学实验结果表明,IκBα可在高效的动力学过程中提高NF-κB从DNA的解离速率。对各种IκB突变蛋白的分析表明,此过程需要C末端PEST序列以及IκBα的弱折叠的第五和第六锚蛋白重复序列​​。这些重复序列的突变稳定作用会降低IκBα提高解离速率的效率。

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