Article
- The EMBO Journal (2007) 26, 436 - 447
- doi:10.1038/sj.emboj.7601489
Published online: 21 December 2006
Subject Categories:
COMMD1 promotes the ubiquitination of NF-
B subunits through a cullin-containing ubiquitin ligase
Gabriel N Maine1,2, Xicheng Mao1,2, Christine M Komarck1,2 and Ezra Burstein1,2,3
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
- Molecular Mechanisms of Disease Program, University of Michigan Medical School, Ann Arbor, MI, USA
- Gastroenterology Section at the Ann Arbor VA Medical Center, Ann Arbor, MI, USA
Correspondence to:
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
Abstract
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.
Keywords:
- COMMD1,
- cullin,
- NF-B,
- transcription,
- ubiquitination
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