Fig. 1.

The process of neddylation modification. a Neddylation is a process that tags the ubiquitin-like small molecule NEDD8 onto its substrate through an enzymatic cascade involving NEDD8-activating enzyme E1, NEDD8-conjugating enzyme E2 and substrate-specific NEDD8 E3 ligases. MLN4924 is a NAE inhibitor that blocks the entire neddylation pathway. b Cullin-RING ligase, consisting of a scaffold cullin, a RING protein that binds to NEDD8-loaded E2, an adaptor, and a substrate receptor, promotes ubiquitylation and degradation of their substrates. N8, NEDD8