Regulation of NF-κB function
Regulation of NF-κB function
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DOI：
10.1042/bss0730165
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Perkins, ND
中科院分区：
文献类型：
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作者：
Campbell, KJ;Perkins, ND
在其发现后的20年里，对NF-κ B（核因子-κ B）转录因子家族的研究揭示了惊人的功能多样性。NF-κ B蛋白是细胞对大量不同刺激的免疫、炎症、应激、增殖和凋亡反应的调节剂。NF-κ B复合物可在所有细胞类型中发现，表明NF-κ B可被诱导的不同环境的数量是巨大的。此外，许多报告表明NF-κ B的功能明显相反或矛盾。很明显，仅仅理解NF-κ B亚基的核定位和DNA结合途径是不够的。如果我们要从整体上理解NF-κ B通路，了解NF-κ B亚基功能的调节也是很重要的。这些问题包括在特定情况下控制NF-κ B调控基因的特异性和时间的机制。他们还包括为什么NF-κ B亚基有时可以抑制而不是激活转录的原因，以及NF-κ B反应如何与细胞中其他重要的转录因子途径整合，如DNA损伤或癌基因激活后p53肿瘤抑制因子的诱导。了解调节NF-κ B功能的机制对于我们理解NF-κ B亚基在人类炎症性疾病和癌症中的作用具有重要意义，并且还可能影响未来基于NF-κ B的临床治疗的使用。
In the 20 years since its discovery, research into the NF-kappa B (nuclear factor-kappa B) family of transcription factors has revealed an amazing diversity of functions. NF-kappa B proteins are regulators of the immune, inflammatory, stress, proliferative and apoptotic responses of a cell to a very large number of different stimuli. NF-kappa B complexes can be found in all cell types, indicating that the number of different contexts in which NF-kappa B can become induced is enormous. Moreover, many reports suggest apparently opposing or contradictory functions for NF-kappa B. It is clear that it is not simply enough to understand the pathways leading to nuclear localization and DNA binding of NF-kappa B subunits. It is also important that we comprehend the regulation of NF-kappa B subunit functionality if we are to understand the NF-kappa B pathway as a whole. These issues include the mechanisms controlling the specificity and timing of genes regulated by NF-kappa B under particular circumstances. They also include the reasons why NF-kappa B subunits can sometimes repress rather than activate transcription and how the NF-kappa B response is integrated with other important transcription factor pathways in the cell, such as the induction of the p53 tumour suppressor following DNA damage or oncogene activation. Understanding the mechanisms that regulate NF-kappa B function has important implications for our understanding of the role that NF-kappa B subunits play in human inflammatory diseases and cancer, and could also impact on the use of future NF-kappa B-based clinical therapies.