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

Lin Feng Chen, Warner C. Greene

Research output: Contribution to journalReview articlepeer-review

Abstract

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

Original languageEnglish (US)
Pages (from-to)549-557
Number of pages9
JournalJournal of Molecular Medicine
Volume81
Issue number9
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

Keywords

  • Acetylation
  • Deacetylation
  • HDAC3
  • NF-κB
  • RelA
  • p300

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Regulation of distinct biological activities of the NF-κB transcription factor complex by acetylation'. Together they form a unique fingerprint.

Cite this