Post-activation Turn-off of NF-κB-dependent Transcription Is Regulated by Acetylation of p65*

By R. Kiernan, V. Brès, Raymond W. M. Ng, M. Coudart, Selma El Messaoudi, C. Sardet, D. Jin, S. Emiliani, M. Benkirane. Journal of Biological Chemistry, 2003

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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 κΒ-DNA. Finally, acetylation of p65 facilitated its removal from DNA and consequently its IκΒα-mediated export from the nucleus. We propose that acetylation of p65 plays a key role in IκΒα-mediated attenuation of NF-κΒ transcriptional activity which is an important process that restores the latent state in post-induced cells.

Subfields: Cancer Research, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/d964ea01d5228dad7a4c458a7073821a79d08815

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Citations in the corpus

Sirtuins: critical regulators at the crossroads between cancer and aging (2007, background): “Phosphorylation of NF-kB on Ser276 recruits HAT-containing complexes to target promoters (Zhong et al., 2002), while acetylation of NF-kB on multiple lysines affects both its DNA binding and transactivation activity (Chen et al., 2002; Kiernan et al., 2003).”
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase (2004, background): “The RelA/p65 protein can be acetylated at five lysine residues, K122, 123, 218, 221, and 310 (Figure 4A) (Chen et al, 2002; Kiernan et al, 2003).”
IκB Kinase α-Mediated Derepression of SMRT Potentiates Acetylation of RelA/p65 by p300 (2006, background): “The transactivation potential and DNA binding activity of RelA/ p65 are regulated by p300-induced acetylation (14, 16, 33, 42, 69, 72).”
NF-κB RelA Phosphorylation Regulates RelA Acetylation (2005, background): “The acetyltransferases p300 and CBP appear to play a major role in the in vivo acetylation of RelA (6, 17 ).”
Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway (2006, background): “RelA is also acetylated at Lys-122 and Lys-123, which has an inhibitory effect (see below) (Kiernan et al., 2003).”