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 language | English (US) |
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Pages (from-to) | 436-447 |
Number of pages | 12 |
Journal | EMBO Journal |
Volume | 26 |
Issue number | 2 |
DOIs | |
State | Published - Jan 24 2007 |
Keywords
- COMMD1
- Cullin
- NF-κB
- Transcription
- Ubiquitination
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology