title: Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB.
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.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, CA 94141, USA.
authors.forename: Lin-feng
authors.initials: LF
authors.lastname: Chen
authors.forename: Yajun
authors.initials: Y
authors.lastname: Mu
authors.forename: Warner C
authors.initials: WC
authors.lastname: Greene
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D051548:Histone Acetyltransferases; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor