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标题：Kinetic enhancement of NF-κB·DNA dissociation by IκBα
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作者：Simon Bergqvist ; Vera Alverdi ; Benedicte Mengel 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：46
页码：19328-19333
DOI：10.1073/pnas.0908797106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：binding kinetics ; disordered proteins ; protein–DNA interaction ; transcription ; surface plasmon resonance