COMMD1 promotes the ubiquitination of NF-κB subunits through a cullin-containing ubiquitin ligase

Gabriel N. Maine, Xicheng Mao, Christine M. Komarck, Ezra Burstein

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

NF-κB is a pleiotropic transcription factor involved in multiple processes, including inflammation and oncogenesis. We have previously reported that COMMD1 represses κB-dependent transcription by negatively regulating NF-κB-chromatin interactions. Recently, ubiquitination of NF-κB subunits has been similarly implicated in the control of NF-κB recruitment to chromatin. We report here that COMMD1 accelerates the ubiquitination and degradation of NF-κB subunits through its interaction with a multimeric ubiquitin ligase containing Elongins B and C, Cul2 and SOCS1 (ECS SOCS1). COMMD1-deficient cells demonstrate stabilization of RelA, greater nuclear accumulation of RelA after TNF stimulation, de-repression of several κB-responsive genes, and enhanced NF-κB-mediated cellular responses. COMMD1 binds to Cul2 in a stimulus-dependent manner and serves to facilitate substrate binding to the ligase by stabilizing the interaction between SOCS1 and RelA. Our data uncover that ubiquitination and degradation of NF-κB subunits by this COMMD1-containing ubiquitin ligase is a novel and critical mechanism of regulation of NF-κB-mediated transcription.

Original languageEnglish (US)
Pages (from-to)436-447
Number of pages12
JournalEMBO Journal
Volume26
Issue number2
DOIs
StatePublished - Jan 24 2007

Keywords

  • COMMD1
  • Cullin
  • NF-κB
  • Transcription
  • Ubiquitination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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