NEDD8 Activating Enzyme (NAE)

NEDD8 activating enzyme (NAE) is a critical E1 enzyme that catalyzes the first step in the neddylation pathway, which involves the conjugation of NEDD8, a ubiquitin-like protein, to target substrates. This post-translational modification regulates various cellular processes by modulating the activity of cullin-RING ligases (CRLs), a major class of E3 ubiquitin ligases. Dysregulation or abnormal activation of the neddylation pathway has been implicated in cancer pathogenesis due to its impact on cell proliferation and survival mechanisms. Inhibition or genetic disruption of NAE leads to accumulation/stabilization of CRL substrates. Several small-molecule inhibitors have been developed targeting NAE, suppressing tumor growth across hematologic malignancies and solid tumors.

Other names

NAE1/APPBP1UBA3

Sulfonyl adenine analog; blocks ATP binding site on NAE; prevents activation/neddylation cascade