Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation

J Mol Med (Berl). 2003 Sep;81(9):549-57. doi: 10.1007/s00109-003-0469-0. Epub 2003 Aug 15.


Although the proximal cytoplasmic signaling events that control the activation of the NF-kappaB transcription factor are understood in considerable detail, the subsequent intranuclear events that regulate the strength and duration of the NF-kappaB-mediated transcriptional response remain poorly defined. Recent studies have revealed that NF-kappaB is subject to reversible acetylation and that this posttranslational modification functions as an intranuclear molecular switch to control NF-kappaB action. In this review, we summarize this new and fascinating mechanism through which the pleiotropic effects of NF-kappaB are regulated within the cells. NF-kappaB is a heterodimer composed of p50 and RelA subunits. Both subunits are acetylated at multiple lysine residues with the p300/CBP acetyltransferases playing a major role in this process in vivo. Further, the acetylation of different lysines regulates different functions of NF-kappaB, including transcriptional activation, DNA binding affinity, IkappaBalpha assembly, and subcellular localization. Acetylated forms RelA are subject to deacetylation by histone deacetylase 3 (HDAC3). This selective action of HDAC3 promotes IkappaBalpha binding and rapid CRM1-dependent nuclear export of the deacetylated NF-kappaB complex, which terminates the NF-kappaB response and replenishes the cytoplasmic pool of latent NF-kappaB/IkappaBalpha complexes. This readies the cell for the next NF-kappaB-inducing stimulus. Thus, reversible acetylation of RelA serves as an important intranuclear regulatory mechanism that further provides for dynamic control of NF-kappaB action.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acetylation
  • Acetyltransferases / pharmacology
  • Animals
  • Cell Cycle Proteins / pharmacology
  • Histone Acetyltransferases
  • Humans
  • NF-kappa B / metabolism*
  • Protein Processing, Post-Translational
  • Transcription Factor RelA
  • Transcription Factors
  • p300-CBP Transcription Factors


  • Cell Cycle Proteins
  • NF-kappa B
  • Transcription Factor RelA
  • Transcription Factors
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor