Department of Microbiology and Immunology, College of Physicians and Surgeons, New York, New York 10032, USA.
Genes Dev. 2012 Feb 1;26(3):203-34. doi: 10.1101/gad.183434.111.
The ability to sense and adjust to the environment is crucial to life. For multicellular organisms, the ability to respond to external changes is essential not only for survival but also for normal development and physiology. Although signaling events can directly modify cellular function, typically signaling acts to alter transcriptional responses to generate both transient and sustained changes. Rapid, but transient, changes in gene expression are mediated by inducible transcription factors such as NF-κB. For the past 25 years, NF-κB has served as a paradigm for inducible transcription factors and has provided numerous insights into how signaling events influence gene expression and physiology. Since its discovery as a regulator of expression of the κ light chain gene in B cells, research on NF-κB continues to yield new insights into fundamental cellular processes. Advances in understanding the mechanisms that regulate NF-κB have been accompanied by progress in elucidating the biological significance of this transcription factor in various physiological processes. NF-κB likely plays the most prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease. As our appreciation of the fundamental role of inflammation in disease pathogenesis has increased, so too has the importance of NF-κB as a key regulatory molecule gained progressively greater significance. However, despite the tremendous progress that has been made in understanding the regulation of NF-κB, there is much that remains to be understood. In this review, we highlight both the progress that has been made and the fundamental questions that remain unanswered after 25 years of study.
感知和适应环境的能力对生命至关重要。对于多细胞生物来说，对外界变化做出反应的能力不仅对于生存，而且对于正常的发育和生理机能都是必不可少的。虽然信号事件可以直接修饰细胞功能，但信号通常作用于改变转录反应，以产生短暂和持续的变化。基因表达的快速但短暂变化是由可诱导的转录因子（如 NF-κB）介导的。在过去的 25 年中，NF-κB 一直是可诱导转录因子的典范，为信号事件如何影响基因表达和生理机能提供了许多见解。自发现它是 B 细胞中κ轻链基因表达的调节剂以来，NF-κB 的研究不断为基本细胞过程提供新的见解。对调节 NF-κB 机制的理解的进展伴随着阐明该转录因子在各种生理过程中的生物学意义的进展。NF-κB 可能在免疫系统的发育和功能中发挥最突出的作用，毫不奇怪，当失调时，它会导致炎症性疾病的病理生理学。随着我们对炎症在疾病发病机制中的基本作用的认识不断提高，NF-κB 作为关键调节分子的重要性也逐渐得到了更多的重视。然而，尽管在理解 NF-κB 的调节方面已经取得了巨大的进展，但仍有许多问题需要进一步研究。在这篇综述中，我们强调了已经取得的进展以及在经过 25 年的研究后仍然存在的未解决的基本问题。
