NF-κB 信号系统的调控逻辑。
The regulatory logic of the NF-kappaB signaling system.
机构信息
Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
出版信息
Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a000216. doi: 10.1101/cshperspect.a000216.
Abstract
NF-kappaB refers to multiple dimers of Rel homology domain (RHD) containing polypeptides, which are controlled by a stimulus-responsive signaling system that mediates the physiological responses to inflammatory intercellular cytokines, pathogen exposure, and developmental signals. The NF-kappaB signaling system operates on transient or short timescales, relevant to inflammation and immune responses, and on longer-term timescales relevant to cell differentiation and organ formation. Here, we summarize our current understanding of the kinetic mechanisms that allow for NF-kappaB regulation at these different timescales. We distinguish between the regulation of NF-kappaB dimer formation and the regulation of NF-kappaB activity. Given the number of regulators and reactions involved, the NF-kappaB signaling system is capable of integrating a multitude of signals to tune NF-kappaB activity, signal dose responsiveness, and dynamic control. We discuss the prevailing mechanisms that mediate signaling cross talk.
摘要
NF-κB 是指含有 Rel 同源结构域 (RHD) 的多种二聚体，由刺激反应性信号系统调控，介导细胞因子的炎症反应、病原体暴露和发育信号等生理反应。NF-κB 信号系统在短暂或短期时间尺度上发挥作用，与炎症和免疫反应有关，在长期时间尺度上与细胞分化和器官形成有关。在这里，我们总结了我们目前对允许 NF-κB 在不同时间尺度上进行调节的动力学机制的理解。我们区分了 NF-κB 二聚体形成的调节和 NF-κB 活性的调节。鉴于涉及的调节因子和反应数量众多，NF-κB 信号系统能够整合多种信号来调节 NF-κB 活性、信号剂量反应性和动态控制。我们讨论了介导信号串扰的流行机制。
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