Journal of Molecular Medicine

, Volume 81, Issue 9, pp 549–557

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

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.

Keywords

Acetylation Deacetylation p300 HDAC3 NF-κB RelA 

Abbreviations

NF-κB

Nuclear factor κB

RHD

Rel homology domain

IKK

IκB kinase complex

TSA

Trichostatin A

HDAC

Histone deacetylase

HAT

Histone acetyltransferase

TNF-α

Tumor necrosis factor α

NCoR

Nuclear receptor corepressor

SMRT

Silencing mediator for retinoid and thyroid hormone receptors

SRC-1, 3

Steroid receptor coactivator 1, 3

NIK

NF-κB-inducing kinase

MEF

Mouse embryo fibroblast

CRM-1

Chromosomal region maintenance-1

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Gladstone Institute of Virology and ImmunologyUniversity of CaliforniaSan FranciscoUSA
  2. 2.Departments of Medicine and of Microbiology and ImmunologyUniversity of CaliforniaSan FranciscoUSA

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