Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65.
NF-kappaB 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-kappaB is tightly regulated by its partner IkappaBalpha. Here, we show that the p65 subunit of NF-kappaB 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 kappaBeta-DNA. Finally, acetylation of p65 facilitated its removal from DNA and consequently its IkappaBetaalpha-mediated export from the nucleus. We propose that acetylation of p65 plays a key role in IkappaBetaalpha-mediated attenuation of NF-kappaBeta transcriptional activity which is an important process that restores the latent state in post-induced cells.
Kiernan
Rosemary
R
Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, Montpellier 34296, France.
Brès
Vanessa
V
Ng
Raymond W M
RW
Coudart
Marie-Pierre
MP
El Messaoudi
Selma
S
Sardet
Claude
C
Jin
Dong-Yan
DY
Emiliani
Stephane
S
Benkirane
Monsef
M
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008239:Lysine / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
D000123:Acetyltransferases; D002843:Chromatin; D004247:DNA; D051548:Histone Acetyltransferases; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D008239:Lysine; D016328:NF-kappa B; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D051996:Transcription Factor RelA; D000099186:Histone Deacetylase 3