Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65

Abstract

NF-κB represents a family of eukaryotic transcription factors participating in the regulation of various cellular genes involved in the immediate early processes of immune, acute-phase, and inflammatory responses. Cellular localization and consequently the transcriptional activity of NF-κB is tightly regulated by its partner IκBα. Here, we show that the p65 subunit of NF-κB is acetylated by both p300 and PCAF on lysines 122 and 123. Both HDAC2 and HDAC3 interact with p65, although only HDAC3 was able to deacetylate p65. Acetylation of p65 reduces its ability to bind κB-DNA. Finally, acetylation of p65 facilitated its removal from DNA and consequently its IκBα-mediated export from the nucleus. We propose that acetylation of p65 plays a key role in IκBα-mediated attenuation of NF-κB transcriptional activity which is an important process that restores the latent state in post-induced cells.