Hoffmann Alexander, Baltimore David
Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Immunol Rev. 2006 Apr;210:171-86. doi: 10.1111/j.0105-2896.2006.00375.x.
Over the past few years, the transcription factor nuclear factor (NF)-kappaB and the proteins that regulate it have emerged as a signaling system of pre-eminent importance in human physiology and in an increasing number of pathologies. While NF-kappaB is present in all differentiated cell types, its discovery and early characterization were rooted in understanding B-cell biology. Significant research efforts over two decades have yielded a large body of literature devoted to understanding NF-kappaB's functioning in the immune system. NF-kappaB has been found to play roles in many different compartments of the immune system during differentiation of immune cells and development of lymphoid organs and during immune activation. NF-kappaB is the nuclear effector of signaling pathways emanating from many receptors, including those of the inflammatory tumor necrosis factor and Toll-like receptor superfamilies. With this review, we hope to provide historical context and summarize the diverse physiological functions of NF-kappaB in the immune system before focusing on recent advances in elucidating the molecular mechanisms that mediate cell type-specific and stimulus-specific functions of this pleiotropic signaling system. Understanding the genetic regulatory circuitry of NF-kappaB functionalities involves system-wide measurements, biophysical studies, and computational modeling.
在过去几年中，转录因子核因子（NF）-κB及其调控蛋白已成为人类生理学以及越来越多病理过程中极为重要的信号系统。虽然NF-κB存在于所有分化的细胞类型中，但其发现和早期特征描述源于对B细胞生物学的理解。二十多年来的大量研究工作产生了大量致力于理解NF-κB在免疫系统中功能的文献。已发现NF-κB在免疫细胞分化、淋巴器官发育以及免疫激活过程中的免疫系统许多不同部分发挥作用。NF-κB是许多受体发出的信号通路的核效应器，包括炎性肿瘤坏死因子和Toll样受体超家族的受体。通过这篇综述，我们希望提供历史背景并总结NF-κB在免疫系统中的多种生理功能，然后重点介绍在阐明介导这种多效性信号系统的细胞类型特异性和刺激特异性功能的分子机制方面的最新进展。理解NF-κB功能的遗传调控回路涉及全系统测量、生物物理研究和计算建模。
