NEDD8-activating enzyme E1 regulatory subunit (NAE1)

NEDD8-activating enzyme E1 regulatory subunit (NAE1) is the regulatory component of the E1 heterodimeric enzyme complex (with UBA3) that catalyzes the first step in activation of NEDD8, a ubiquitin-like protein. This activation, termed neddylation, is essential for regulating cell cycle progression, viability, cell growth, and DNA repair mechanisms. NAE1 binds the amyloid precursor protein and has been implicated in neuronal functions and in the pathogenesis of Alzheimer’s disease, as well as in cancer where inhibition of NAE1 is being clinically pursued. Pevonedistat, an NAE inhibitor, blocks neddylation and impairs DNA repair and cell cycle progression, particularly in cancer cells. Overexpression of NAE1 leads to deregulated cell cycle and apoptosis, underlining its role as a mechanistically and therapeutically relevant target in oncology, neurobiology, and cellular homeostasis

Other names

Amyloid beta precursor protein-binding protein 1, 59 kDaAPPBP1Amyloid protein-binding protein 1Proto-oncogene protein 1ula-1HPP1A-116A10.1

Inhibition of NEDD8-activating enzyme, leading to disruption of neddylation, impaired protein degradation, and cell cycle arrest; Pevonedistat forms an inhibitory covalent adduct with NEDD8 in the NAE active site, blocking the enzyme’s activity