The IκB-NF-κB signaling module:: Temporal control and selective gene activation
The IκB-NF-κB signaling module:: Temporal control and selective gene activation
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DOI：
10.1126/science.1071914
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发表时间：
2002-11-08
期刊：
影响因子：
56.9
通讯作者：
Baltimore, D
中科院分区：
文献类型：
--
作者：
Hoffmann, A;Levchenko, A;Baltimore, D
转录激活因子NF-κ B（核因子κ B）的核定位在哺乳动物细胞中由NF-κ B抑制蛋白的三种亚型控制：I κ B α、I κ B β和I κ B β。基于简化减少敲除细胞系中的IkappaB-NF-kappaB信号传导模块，我们提出了一个计算模型，该模型描述了协调降解和IkappaB蛋白合成的NF-kappaB激活的时间控制。该模型表明，IkappaBalpha是负责强负反馈，允许快速关闭的NF-κ B反应，而IkappaBbeta和β-κ B功能，以减少系统的振荡电位和稳定NF-κ B反应在较长的刺激。双峰信号处理特性相对于刺激持续时间的模型显示，并产生特异性基因表达。
Nuclear localization of the transcriptional activator NFkappa-B (nuclear factor kappaB) is controlled in mammalian cells by three isoforms of NF-kappaB inhibitor protein: IkappaBalpha, -beta, and -epsilon. Based on simplifying reductions of the IkappaB-NF-kappaB signaling module in knockout cell lines, we present a computational model that describes the temporal control of NF-kappaB activation by the coordinated degradation and synthesis of IkappaB proteins. The model demonstrates that IkappaBalpha is responsible for strong negative feedback that allows for a fast turn-off of the NF-kappaB response, whereas IkappaBbeta and -epsilon function to reduce the system's oscillatory potential and stabilize NF-kappaB responses during longer stimulations. Bimodal signal-processing characteristics with respect to stimulus duration are revealed by the model and are shown to generate specificity in gene expression.