Ubiquitin-like protein NEDD8

NEDD8 is a ubiquitin-like protein that functions as a post-translational modifier of cellular proteins, particularly cullins and p53/TP53 (UniProt: Q15843). Through neddylation of cullins, NEDD8 regulates cullin-RING E3 ubiquitin ligase complexes and facilitates proteasomal degradation of cell cycle regulators and other proteins. NEDD8 conjugation to p53/TP53 inhibits its transcriptional activity and requires activation by the E1 complex UBE1C-APPBP1 and E2 enzyme UBE2M.

NEDD8 is involved in cell cycle control and embryogenesis via its conjugation to a limited set of cellular substrates. No curated diseases are listed in UniProt for this protein.

NEDD8 shows downregulation in Alzheimer's disease brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.29 based on TMT-labeled quantitative proteomics across four subcellular fractions. This reduced neddylation capacity may impact proteasomal protein turnover pathways relevant to neurodegeneration.