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| Subject Categories: Chromatin & Transcription | Proteins |
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| The EMBO Journal
(2007) 26, 436–447, doi:10.1038/sj.emboj.7601489 Published online 21 December 2006 |
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COMMD1 promotes the ubiquitination of NF- B subunits through a cullin-containing ubiquitin ligase |
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| Gabriel N Maine1, 2, Xicheng Mao1, 2, Christine M Komarck1, 2 and Ezra Burstein1, 2, 3 |
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1 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA 2 Molecular Mechanisms of Disease Program, University of Michigan Medical School, Ann Arbor, MI, USA 3 Gastroenterology Section at the Ann Arbor VA Medical Center, Ann Arbor, MI, USA To whom correspondence should be addressed Ezra Burstein, 109 Zina Pitcher Place, 1526 BSRB, Ann Arbor, MI 48109-2200, USA. Tel.: +1 734 647 9853; Fax: +1 734 615 4022; E-mail: ezrab@umich.edu Received 29 June 2006; Accepted 9 November 2006; Published online 21 December 2006. |
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| Abstract |
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| NF-B is a pleiotropic transcription factor involved in multiple processes, including inflammation and oncogenesis. We have previously reported that COMMD1 represses B-dependent transcription by negatively regulating NF-B–chromatin interactions. Recently, ubiquitination of NF-B subunits has been similarly implicated in the control of NF-B recruitment to chromatin. We report here that COMMD1 accelerates the ubiquitination and degradation of NF-B subunits through its interaction with a multimeric ubiquitin ligase containing Elongins B and C, Cul2 and SOCS1 (ECSSOCS1). COMMD1-deficient cells demonstrate stabilization of RelA, greater nuclear accumulation of RelA after TNF stimulation, de-repression of several B-responsive genes, and enhanced NF-B-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-B subunits by this COMMD1-containing ubiquitin ligase is a novel and critical mechanism of regulation of NF-B-mediated transcription. |
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| Keywords: COMMD1, cullin, NF-B, transcription, ubiquitination |
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