title: COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding.
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.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Xicheng
authors.initials: X
authors.lastname: Mao
authors.forename: Nathan
authors.initials: N
authors.lastname: Gluck
authors.forename: Baozhi
authors.initials: B
authors.lastname: Chen
authors.forename: Petro
authors.initials: P
authors.lastname: Starokadomskyy
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Maine
authors.forename: Ezra
authors.initials: E
authors.lastname: Burstein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C486317:CAND1 protein, human; C480519:COMMD1 protein, human; C105153:CUL2 protein, human; D044842:Cullin Proteins; D046912:Multiprotein Complexes; D014157:Transcription Factors