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PMID: 12456660 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB.

The EMBO journal ·Vol. 21 ·No. 23 ·2002-12-02 ·Pages 6539-48

Chen LF, Mu Y, Greene WC

Abstract

The nuclear function of the heterodimeric NF-kappaB transcription factor is regulated in part through reversible acetylation of its RelA subunit. We now demonstrate that the p300 and CBP acetyltransferases play a major role in the in vivo acetylation of RelA, principally targeting lysines 218, 221 and 310 for modification. Analysis of the functional properties of hypoacetylated RelA mutants containing lysine-to-arginine substitutions at these sites and of wild-type RelA co-expressed in the presence of a dominantly interfering mutant of p300 reveals that acetylation at lysine 221 in RelA enhances DNA binding and impairs assembly with IkappaBalpha. Conversely, acetylation of lysine 310 is required for full transcriptional activity of RelA in the absence of effects on DNA binding and IkappaBalpha assembly. Together, these findings highlight how site-specific acetylation of RelA differentially regulates distinct biological activities of the NF-kappaB transcription factor complex.

MeSH Terms
Acetylation Acetyltransferases/metabolism Cell Cycle Proteins/metabolism Cell Nucleus/metabolism Enhancer Elements, Genetic Histone Acetyltransferases Mutation NF-kappa B/genetics,metabolism Transcription Factor RelA Transcription Factors p300-CBP Transcription Factors
Chemicals
Cell Cycle Proteins NF-kappa B Transcription Factor RelA Transcription Factors Acetyltransferases Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chen Lin-feng
Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, CA 94141, USA.
Mu Yajun
Greene Warner C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf660
Published
2002-12-02
Pages
6539-48
Language
English
Region
England
NLM ID
8208664
PMCID
PMC136963
Subset
IM
Grants
NIMH NIH HHS · P30 MH59037 · United States
External Links
PubMed source DOI: 10.1093/emboj/cdf660 PMC Full Text View journal details
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