Protection of cullin-RING E3 ligases by CSN-UBP12.
Neddylation, a process that conjugates the ubiquitin-like polypeptide NEDD8 to cullin proteins, activates cullin-RING ubiquitin ligases (CRLs). Deneddylation, in which the COP9 signalosome (CSN) removes NEDD8 from cullins, inactivates CRLs. However, genetic studies of CSN function conclude that deneddylation also promotes CRL activity. It has been proposed that a cyclic transition through neddylation and deneddylation is required for the regulation of CRL activity in vivo. Recent discoveries suggest that an additional level of complexity exists, whereby CRL components are targets for degradation, mediated either by autocatalytic ubiquitination or by unknown mechanisms. Deneddylation by CSN and deubiquitylation by CSN-associated ubiquitin-specific protease 12 protect CRL components from cellular depletion, thus maintaining the physiological CRL activities.
Wu
June-Tai
JT
Institute of Molecular Biology, Academia Sinica, 115 Taipei, Taiwan.
Chan
Ya-Ru
YR
Chien
Cheng-Ting
CT
D000818:Animals; D029681:Arabidopsis Proteins / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D044842:Cullin Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
D029681:Arabidopsis Proteins; C488785:CAND1 protein, Arabidopsis; D044842:Cullin Proteins; D046912:Multiprotein Complexes; C513170:RUB1 protein, Arabidopsis; D025801:Ubiquitin; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex