Journal of Biological Chemistry
Volume 286, Issue 37, 16 September 2011, Pages 32355-32365
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Cell Biology
COMMD1 (Copper Metabolism MURR1 Domain-containing Protein 1) Regulates Cullin RING Ligases by Preventing CAND1 (Cullin-associated Nedd8-dissociated Protein 1) Binding*

https://doi.org/10.1074/jbc.M111.278408Get rights and content
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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.

E3 Ubiquitin Ligase
Protein Degradation
Ubiquitin
Ubiquitin Ligase
Ubiquitination
CAND1
COMMD1
Cul1
Cul2
Cullin

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*

This work was supported, in whole or in part, by National Institutes of Health Grant R01 DK073639. This work was also supported by Crohn's and Colitis Foundation of America Grant SRA 2737 and a University of Texas Southwestern Medical Center DOCS Award (to E. B.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

1

Both authors contributed equally to this work.