COMMD1 (Copper Metabolism MURR1 Domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding

Xicheng Mao, Nathan Gluck, Baozhi Chen, Petro Starokadomskyy, Haiying Li, Gabriel N. Maine, Ezra Burstein

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Cullin RING ligases (CRLs), the most prolific class of ubiquitin ligase enzymes, are multimeric complexes that regulate a wide range of cellular processes. CRL activity is regulated by CAND1 (Cullin-associated Nedd8-dissociated protein 1), an inhibitor that promotes the dissociation of substrate receptor components from the CRL. We demonstrate here that COMMD1 (copper metabolism MURR1 domain-containing 1), a factor previously found to promote ubiquitination of various substrates, regulates CRL activation by antagonizing CAND1 binding. We show that COMMD1 interacts with multiple Cullins, that the COMMD1-Cul2 complex cannot bind CAND1, and that, conversely, COMMD1 can actively displace CAND1 from CRLs. These findings highlight a novel mechanism of CRL activation and suggest that CRL regulation may underlie the pleiotropic activities of COMMD1.

Original languageEnglish (US)
Pages (from-to)32355-32365
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number37
DOIs
StatePublished - Sep 16 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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