Kinetic enhancement of NF-κB•DNA dissociation by IκBα
Kinetic enhancement of NF-κB•DNA dissociation by IκBα
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DOI：
10.1073/pnas.0908797106
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发表时间：
2009-11-17
影响因子：
11.1
通讯作者：
Komives, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Bergqvist, Simon;Alverdi, Vera;Komives, Elizabeth A.
NF-κ B对炎性细胞因子的转录应答的标志是显著快速的强烈活化和随后的信号抑制。尽管I κ B α基因被NF-κ B强烈诱导的事实部分地解释了诱导后阻遏的快速性，但是新合成的I κ B α仍然必须进入细胞核并与DNA中非常大量的κ B位点竞争结合NF-κ B。我们目前的结果，从实时结合动力学实验，表明I κ B α增加了NF-κ B从DNA的解离速率在一个高效的动力学过程。各种I κ B突变蛋白的分析表明，该过程需要C-末端PEST序列和I κ B α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性降低了I κ B α增强解离速率的效率。
A hallmark of the NF-kappa B transcription response to inflammatory cytokines is the remarkably rapid rate of robust activation and subsequent signal repression. Although the rapidity of postinduction repression is explained partly by the fact that the gene for I kappa B alpha is strongly induced by NF-kappa B, the newly synthesized I kappa B alpha still must enter the nucleus and compete for binding to NF-kappa B with the very large number of kappa B sites in the DNA. We present results from real-time binding kinetic experiments, demonstrating that I kappa B alpha increases the dissociation rate of NF-kappa B from the DNA in a highly efficient kinetic process. Analysis of various I kappa B mutant proteins shows that this process requires the C-terminal PEST sequence and the weakly folded fifth and sixth ankyrin repeats of I kappa B alpha. Mutational stabilization of these repeats reduces the efficiency with which I kappa B alpha enhances the dissociation rate.