Ubiquitin-like protein NEDD8 (NEDD8)

Ubiquitin-like protein NEDD8 is a small protein modifier highly homologous to ubiquitin and central to the neddylation pathway, a specialized post-translational modification process[3][4][5]. Through neddylation, NEDD8 covalently attaches to target proteins, most notably cullin family subunits of Cullin-RING E3 ubiquitin ligases, modulating their activity and enabling proper cell cycle regulation, embryogenesis, and cellular response to stress[3][4][5]. Dysregulation of NEDD8 or the neddylation machinery is implicated in tumorigenesis and other diseases, making components of the neddylation pathway (such as NEDD8, its activating enzyme NAE, and conjugating enzymes) attractive therapeutic targets. The first-in-class drug Pevonedistat (MLN4924) inhibits NAE, thereby blocking neddylation and CRL ligase activity, resulting in antitumor effects but with characteristic safety concerns including myelosuppression[3][5][4].

Other names

NEDD8NEDD-8Nedd-8NeddylinNeural precursor cell expressed developmentally down-regulated protein 8NEDD8 ubiquitin like modifierNEDD8, ubiquitin-like protein NEDD8neddylinneural precursor cell expressed, developmentally down-regulated 8ubiquitin-like protein Nedd8

Inhibition of NEDD8-activating enzyme (NAE), leading to blockade of neddylation and suppression of cullin-RING ligase activity; this stabilizes substrates such as cell cycle inhibitors and induces apoptosis or cell cycle arrest in cancer cells[3][5].