Linked Life Data

12920522

Source:http://linkedlifedata.com/resource/pubmed/id/12920522

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-9-23
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0946-2716
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
549-57
pubmed:dateRevised
2011-7-8
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation.
pubmed:affiliation
Gladstone Institute of Virology and Immunology, University of California, P.O. Box 419100, San Francisco, CA 94141-9100, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't