GCN5 is a required cofactor for a ubiquitin ligase that targets NF-κB/RelA

Xicheng Mao, Nathan Gluck, Duo Li, Gabriel N. Maine, Haiying Li, Iram W. Zaidi, Aparna Repaka, Marty W. Mayo, Ezra Burstein

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The transcription factor NF-κB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-κB subunits plays an important role in the termination of NF-κB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism Murr1 Domain 1 (COMMD1) and Cul2. We report here that GCN5, a histone acetyltransferase, associates with COMMD1 and other components of the ligase, promotes RelA ubiquitination, and represses κB-dependent transcription. In this role, the acetyltransferase activity of GCN5 is not required. Interestingly, GCN5 binds more avidly to RelA after phosphorylation on Ser 468, an event that is dependent on IKK activity. Consistent with this, we find that both GCN5 and the IκB Kinase (IKK) complex promote RelA degradation. Collectively, the data indicate that GCN5 participates in the ubiquitination process as an accessory factor for a ubiquitin ligase, where it provides a novel link between phosphorylation and ubiquitination.

Original languageEnglish (US)
Pages (from-to)849-861
Number of pages13
JournalGenes and Development
Volume23
Issue number7
DOIs
StatePublished - Apr 1 2009

Fingerprint

Ubiquitination
Ligases
Ubiquitin
Copper
Phosphorylation
Acetyltransferases
Cell Survival
Transcription Factors
Phosphotransferases

Keywords

  • COMMD1
  • Cul2
  • GCN5
  • NF-κB
  • RelA
  • Ubiquitin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Medicine(all)

Cite this

GCN5 is a required cofactor for a ubiquitin ligase that targets NF-κB/RelA. / Mao, Xicheng; Gluck, Nathan; Li, Duo; Maine, Gabriel N.; Li, Haiying; Zaidi, Iram W.; Repaka, Aparna; Mayo, Marty W.; Burstein, Ezra.

In: Genes and Development, Vol. 23, No. 7, 01.04.2009, p. 849-861.

Research output: Contribution to journalArticle

Mao, X, Gluck, N, Li, D, Maine, GN, Li, H, Zaidi, IW, Repaka, A, Mayo, MW & Burstein, E 2009, 'GCN5 is a required cofactor for a ubiquitin ligase that targets NF-κB/RelA', Genes and Development, vol. 23, no. 7, pp. 849-861. https://doi.org/10.1101/gad.1748409
Mao, Xicheng ; Gluck, Nathan ; Li, Duo ; Maine, Gabriel N. ; Li, Haiying ; Zaidi, Iram W. ; Repaka, Aparna ; Mayo, Marty W. ; Burstein, Ezra. / GCN5 is a required cofactor for a ubiquitin ligase that targets NF-κB/RelA. In: Genes and Development. 2009 ; Vol. 23, No. 7. pp. 849-861.
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