COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex

Stable Identifier
R-HSA-8955285
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

COMMD1 is a member of a family of 10 copper metabolism MURR1 domain-containing proteins that have pleiotropic roles in copper metabolism, NF kappa beta-mediated transcription, the hypoxic response and electrolyte transport (Burstein et al, 2005; reviewed in Maine and Burstein, 2007). COMMD proteins have differential tissue and expression levels, but appear to have partially overlapping function and form homo- and heterodimers through the shared COMM domain (Burstein et al, 2005). COMMD1 and other family members interact with the cullin subunit of CRL E3 ubiquitin ligase complexes, as well as with CCDC22, a protein implicated in X-linked intellectual disability that may regulate COMMD localization. Together, COMMD proteins and CCDC22 activate the ubiquitin ligase activity of CRL complexes by displacing the CAND1 inhibitor (Burstein et al, 2005; Maine et al, 2007; Mao et al, 2011; Starokadomskyy et al, 2013;Phillips-Krawczak et al, 2015). The specificity of interaction between various COMMD and CUL family members may serve to fine tune the regulation of CRL activation, although these details remain to be determined.

Literature References
PubMed ID Title Journal Year
21778237 COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding

Mao, X, Gluck, N, Chen, B, Starokadomskyy, P, Li, H, Maine, GN, Burstein, E

J. Biol. Chem. 2011
17183367 COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase

Maine, GN, Mao, X, Komarck, CM, Burstein, E

EMBO J. 2007
23563313 CCDC22 deficiency in humans blunts activation of proinflammatory NF-?B signaling

Starokadomskyy, P, Gluck, N, Li, H, Chen, B, Wallis, M, Maine, GN, Mao, X, Zaidi, IW, Hein, MY, McDonald, FJ, Lenzner, S, Zecha, A, Ropers, HH, Kuss, AW, McGaughran, J, Gecz, J, Burstein, E

J. Clin. Invest. 2013
17497243 COMMD proteins: COMMing to the scene

Maine, GN, Burstein, E

Cell. Mol. Life Sci. 2007
15799966 COMMD proteins, a novel family of structural and functional homologs of MURR1

Burstein, E, Hoberg, JE, Wilkinson, AS, Rumble, JM, Csomos, RA, Komarck, CM, Maine, GN, Wilkinson, JC, Mayo, MW, Duckett, CS

J. Biol. Chem. 2005
25355947 COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A

Phillips-Krawczak, CA, Singla, A, Starokadomskyy, P, Deng, Z, Osborne, DG, Li, H, Dick, CJ, Gomez, TS, Koenecke, M, Zhang, JS, Dai, H, Sifuentes-Dominguez, LF, Geng, LN, Kaufmann, SH, Hein, MY, Wallis, M, McGaughran, J, Gecz, J, Sluis, Bv, Billadeau, DD, Burstein, E

Mol. Biol. Cell 2015
Participants
Participant Of
hasEvent
Orthologous Events
Authored
Reviewed