Research ArticleImmunology

Negative regulation of NF-κB p65 activity by serine 536 phosphorylation

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Science Signaling  23 Aug 2016:
Vol. 9, Issue 442, pp. ra85
DOI: 10.1126/scisignal.aab2820

IKK is the start and stop signal

By phosphorylating inhibitor of κB (IκB), the kinase IKK targets it for destruction, thus enabling the dimeric transcription factor nuclear factor κB (NF-κB) to translocate to the nucleus and alter target gene expression. Pradère et al. generated knock-in mice expressing a mutant p65 subunit of NF-κB that could not be phosphorylated by IKK at Ser534 (the mouse homolog of human p65 Ser536). The mutated p65 translocated to the nucleus properly, but the protein exhibited enhanced stability, which resulted in exacerbated responses to inflammatory stimuli in vivo. Experiments with human cells indicated that this regulatory mechanism was conserved. Thus, in addition to stimulating NF-κB signaling by phosphorylating IκB, IKK limits inflammation by targeting this regulatory site in mouse and human p65.

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