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. 2016 Mar 18;5(1):12.
doi: 10.3390/cells5010012.

The Regulation of NF-κB Subunits by Phosphorylation

Free PMC article

The Regulation of NF-κB Subunits by Phosphorylation

Frank Christian et al. Cells. .
Free PMC article


The NF-κB transcription factor is the master regulator of the inflammatory response and is essential for the homeostasis of the immune system. NF-κB regulates the transcription of genes that control inflammation, immune cell development, cell cycle, proliferation, and cell death. The fundamental role that NF-κB plays in key physiological processes makes it an important factor in determining health and disease. The importance of NF-κB in tissue homeostasis and immunity has frustrated therapeutic approaches aimed at inhibiting NF-κB activation. However, significant research efforts have revealed the crucial contribution of NF-κB phosphorylation to controlling NF-κB directed transactivation. Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-κB for therapeutic benefit. This review will focus on the phosphorylation of the NF-κB subunits and the impact on NF-κB function.

Keywords: NF-κB; kinase; phosphorylation; transcription factor.


Figure 1
Figure 1
Phosphorylation of the NF-κB subunits. Shown are schematic diagrams of the five members of the NF-κB family: p65 (RelA), RelB, c-Rel, p100 (p52) and p105 (p50). Arrows indicate the C-terminal residues of p50 and p52, which are generated following p105 and p52 processing, respectively. The principal structural motifs for each subunit are indicated, which include the REL homology domain (RHD); transactivation domain (TAD); ankyrin repreat domain (Ank); death domain (DD) and leucine zipper domain (LZ). Phosphorylations that have been shown to regulate NF-κB activity are mapped to each subunit indicating their location relative to each structural motif. The numbering of amino acids corresponds to the human protein sequence.

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