Cullin-RING ubiquitin E3 ligase complexes are the largest family of E3 ligases, and their activation requires modification of the cullin subunit through the ubiquitin-like protein NEDD8. Lower organisms have single DCN1 homologues that promote the neddylation of all cullins but mammalian cells express five DCN-like (DCNL) proteins; the reason for this discrepancy, however, is unclear. In their Research Article in this issue (p. 1441), Thimo Kurz and colleagues explore the specificity and interactions of the different mammalian DCNL homologues. The authors show that, in cultured cells, DCNLs can form stable complexes with cullins and CAND1, a protein that inhibits cullin neddylation, and these complexes can only be neddylated in the presence of a substrate adaptor. The authors also report that all DCNLs are expressed in the cultured cells and interact with most cullins. However, DCNLs have unique subcellular localisations, and their expression in mouse tissue is shown to be much more restricted. DCNL1 is the only DCNL to be widely expressed, suggesting that DCNLs have tissue-specific functions that are not apparent in cultured cells. These data provide new insights into the regulation of inactive cullin complexes, suggesting that, rather than being redundant, DCNLs instead neddylate distinct cullin subpopulations.
- © 2016. Published by The Company of Biologists Ltd