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  • The EMBO Journal (2002) 21, 6539 - 6548
  • doi:10.1093/emboj/cdf660

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

Lin-feng Chen1, Yajun Mu1 and Warner C. Greene1,2,3

  1. Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, CA 94141, USA
  2. Department of Medicine, University of California at San Francisco, San Francisco, CA 94141, USA
  3. Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94141, USA

Correspondence to:

Warner C. Greene, E-mail: wgreene@gladstone.ucsf.edu

Received 7 June 2002; Accepted 18 October 2002; Revised 16 September 2002

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.

  • Keywords:

    • acetylation,
    • deacetylation,
    • IkappaBalpha,
    • p300,
    • RelA