NEDD8
Description
The NEDD8 (NEDD8 ubiquitin like modifier) is a protein-coding gene located on chromosome 14.
NEDD8 is a protein encoded by the NEDD8 gene in humans, known as Rub1 in Saccharomyces cerevisiae. This ubiquitin-like (UBL) protein undergoes covalent conjugation to a limited number of cellular proteins, a process termed NEDDylation, which is analogous to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity with ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. NEDDylation is critical for the recruitment of E2 to the ligase complex, facilitating ubiquitin conjugation. Therefore, NEDD8 modification has been implicated in cell cycle progression and cytoskeletal regulation.
NEDD8, like ubiquitin and SUMO, is conjugated to cellular proteins after its C-terminal tail is processed. The NEDD8 activating E1 enzyme is a heterodimer composed of APPBP1 and UBA3 subunits. The APPBP1/UBA3 enzyme exhibits homology to the N- and C-terminal halves of the ubiquitin E1 enzyme, respectively. The UBA3 subunit contains the catalytic center and activates NEDD8 in an ATP-dependent reaction by forming a high-energy thiolester intermediate.
NEDD8, also known as NEDDylation, is a ubiquitin-like protein that plays a key role in regulating cell cycle control and embryonic development. It achieves this by attaching itself to a limited set of cellular proteins, including cullins and p53/TP53. The attachment of NEDD8 to cullins is crucial for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, which ultimately facilitates polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. Conversely, the attachment of NEDD8 to p53/TP53 inhibits its transcriptional activity. The covalent attachment of NEDD8 to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M.
NEDD8 is also known as NEDD-8.
