Diamant Gil, Dikstein Rivka
Dept. of Biological Chemistry, The Weizmann Institute of Science, Rehovot , Israel.
Biochim Biophys Acta. 2013 Sep;1829(9):937-45. doi: 10.1016/j.bbagrm.2013.04.007. Epub 2013 Apr 25.
The NF-κB family of transcription factors governs the cellular reaction to a variety of extracellular signals. Following stimulation, NF-κB activates genes involved in inflammation, cell survival, cell cycle, immune cell homeostasis and more. This review focuses on studies of the past decade that uncover the transcription elongation process as a key regulatory stage in the activation pathway of NF-κB. Of interest are studies that point to the elongation phase as central to the selectivity of target gene activation by NF-κB. Particularly, the cascade leading to phosphorylation and acetylation of the NF-κB subunit p65 on serine 276 and lysine 310, respectively, was shown to mediate the recruitment of Brd4 and P-TEFb to many pro-inflammatory target genes, which in turn facilitate elongation and mRNA processing. On the other hand, some anti-inflammatory genes are refractory to this pathway and are dependent on the elongation factor DSIF for efficient elongation and mRNA processing. While these studies have advanced our knowledge of NF-κB transcriptional activity, they have also raised unresolved issues regarding the specific genomic and physiological contexts by which NF-κB utilizes different mechanisms for activation.
转录因子NF-κB家族调控细胞对多种细胞外信号的反应。受到刺激后，NF-κB会激活参与炎症、细胞存活、细胞周期、免疫细胞稳态等过程的基因。本综述聚焦于过去十年的研究，这些研究揭示了转录延伸过程是NF-κB激活途径中的关键调控阶段。有趣的是，一些研究指出延伸阶段是NF-κB激活靶基因选择性的核心。特别是，分别导致NF-κB亚基p65的丝氨酸276和赖氨酸310磷酸化和乙酰化的级联反应，被证明介导了Brd4和P-TEFb募集到许多促炎靶基因上，进而促进延伸和mRNA加工。另一方面，一些抗炎基因对该途径不敏感，并且依赖延伸因子DSIF进行有效的延伸和mRNA加工。虽然这些研究增进了我们对NF-κB转录活性的了解，但它们也提出了一些尚未解决的问题，即NF-κB在特定基因组和生理背景下利用不同激活机制的问题。
