title: Protein neddylation: beyond cullin-RING ligases.
abstract: NEDD8 (neural precursor cell expressed developmentally downregulated protein 8) is a ubiquitin-like protein that activates the largest ubiquitin E3 ligase family, the cullin-RING ligases. Many non-cullin neddylation targets have been proposed in recent years. However, overexpression of exogenous NEDD8 can trigger NEDD8 conjugation through the ubiquitylation machinery, which makes validating potential NEDD8 targets challenging. Here, we re-evaluate studies of non-cullin targets of NEDD8 in light of the current understanding of the neddylation pathway, and suggest criteria for identifying genuine neddylation substrates under homeostatic conditions. We describe the biological processes that might be regulated by non-cullin neddylation, and the utility of neddylation inhibitors for research and as potential therapies. Understanding the biological significance of non-cullin neddylation is an exciting research prospect primed to reveal fundamental insights.
authors.affiliation: ETH Zurich, Institute of Biochemistry, Department of Biology, Otto-Stern-Weg 3, CH-8093 Zurich, Switzerland.
authors.forename: Radoslav I
authors.initials: RI
authors.lastname: Enchev
authors.affiliation: Department of Structural Biology and Howard Hughes Medical Institute, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Schulman
authors.affiliation: ETH Zurich, Institute of Biochemistry, Department of Biology, Otto-Stern-Weg 3, CH-8093 Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D000818:Animals; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000075687:NEDD8 Protein; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D044842:Cullin Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins