Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha.
Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha.
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DOI：
10.1021/bi901948j
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发表时间：
2010-03-02
期刊：
影响因子：
2.9
通讯作者：
Komives, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Ferreiro, Diego U.;Komives, Elizabeth A.
转录因子 NF-κB 家族通过快速转录激活和随后的信号抑制来响应炎症细胞因子。系统控制的大部分取决于其主要抑制剂 IκBα 的独特特征，IκBα 似乎具有折叠动力学，这是其活性的生物物理特性的基础。理论折叠研究和实验表明，IκBα 的锚蛋白重复结构域的一部分在结合时折叠。在静息细胞中，IκBα 不断被合成，但大部分会迅速降解，仅留下极少量的游离 IκBα。几乎所有 NF-κB 都与 IκBα 结合，导致核定位和转录激活几乎完全受到抑制。结合溶液生物物理测量和细胞内定量蛋白质半衰期测量，使我们能够了解抑制是如何发生的、为什么 IκBα 在游离状态下可以快速降解但在结合状态下保持极其稳定，以及如何通过 IκB 折叠动力学来调节信号激活和抑制。这篇综述总结了体外和体内实验的结果，这些实验集中证明了生物物理学和细胞生物学之间在理解 NF-κB 信号模块的转录控制方面的有效相互作用。
The NF-κB family of transcription factors responds to inflammatory cytokines with rapid transcriptional activation and subsequent signal repression. Much of the system control depends on the unique characteristics of its major inhibitor, IκBα, which appears to have folding dynamics that underlie the biophysical properties of its activity. Theoretical folding studies followed by experiments have shown that a portion of the ankyrin repeat domain of IκBα folds on binding. In resting cells, IκBα is constantly being synthesized but most of it is rapidly degraded leaving only a very small pool of free IκBα. Nearly all of the NF-κB is bound to IκBα resulting in near complete inhibition of nuclear localization and transcriptional activation. Combined solution biophysical measurements and quantitative protein half-life measurements inside cells have allowed us to understand how the inhibition occurs, why IκBα can be degraded quickly in the free state but remain extremely stable in the bound state, and how signal activation and repression can be tuned by IκB folding dynamics. This review summarizes results of in vitro and in vivo experiments that converge demonstrating the effective interplay between biophysics and cell biology in understanding transcriptional control by the NF-κB signaling module.
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影响因子：
5.6
作者：
Binz, HK;Stumpp, MT;Plückthun, A
通讯作者：
Plückthun, A
影响因子：
64.5
作者：
Huxford, T;Huang, DB;Ghosh, G
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DOI：
10.1073/pnas.90.6.2532
发表时间：
1993-03-15
影响因子：
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作者：
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通讯作者：
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作者：
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影响因子：
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