NEDD8

Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.

Neural Precursor Cell Expressed, Developmentally Down-Regulated 8

Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis via its conjugation to a limited number of cellular proteins, such as cullins or p53/TP53 (PubMed:9694792, PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:15242646, PubMed:14690597).

Attachment of NEDD8 to cullins is critical for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, thus facilitating polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins (PubMed:9694792, PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:20688984).

Attachment of NEDD8 to p53/TP53 inhibits p53/TP53 transcriptional activity (PubMed:15242646).

Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M (PubMed:14690597).

Anatomical structure morphogenesis Source: ProtInc
Cellular protein modification process Source: ProtInc
Modification-dependent protein catabolic process Source: GO_Central
Protein localization Source: Ensembl
Protein neddylation Source: MGI
Proteolysis Source: ProtInc
Regulation of proteolysis Source: GO_Central
Regulation of transcription by RNA polymerase II Source: Ensembl
Ubiquitin-dependent protein catabolic process Source: ProtInc

Nucleus
Note: Mainly nuclear.

Cleavage of precursor form by UCHL3 or SENP8 is necessary for function.
(Microbial infection) Deamidated at Gln-40 by bacterial cyclomodulin Cif produced by enteropathogenic E.coli, Y.pseudotuberculosis or B.pseudomallei, leading to impair NEDD8 ability to activate cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (PubMed:20688984, PubMed:21903097, PubMed:23589306, PubMed:26632597, PubMed:23175788). Deamidation occurs on NEDD8-modified cullins (PubMed:20850415, PubMed:21903097). NEDD8 deamidation prevents switching from the inactive to active state by maintaining the 'closed' structure of the CRL complexes (PubMed:23589306, PubMed:26632597). Deamidation may also impair its deconjugation by the COP9 signalosome; However this result needs additional evidences (PubMed:20850415, PubMed:21903097).