Transcriptional Control by NF-kappa B: Elongation in Focus

The NF-kappa B family of transcription factors governs the cellular reaction to a variety of extracellular signals. Following stimulation, NF-kappa B 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-kappa B. Of interest are studies that point to the elongation phase as central to the selectivity of target gene activation by NF-kappa B. Particularly, the cascade leading to phosphorylation and acetylation of the NF-kappa B 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 rnRNA processing. While these studies have advanced our knowledge of NF-kappa B transcriptional activity, they have also raised unresolved issues regarding the specific genomic and physiological contexts by which NF-kappa B utilizes different mechanisms for activation. (c) 2013 Elsevier B.V. All rights reserved.