The neddylation conjugation pathway has a pivotal role in mediating 
ubiquitination of proteins and regulation of numerous biological processes. 
Dysregulation in the ubiquitination and neddylation pathways is associated with 
many cancers. Ubiquitination involves covalent attachment of ubiquitin to target 
proteins, leading to protein degradation by the proteasome system. The activity 
of the E3-ubiquitin ligase family, cullin-RING ligases, is essential for 
promoting ubiquitin transfer to the appropriate substrates. Neddylation, a 
process mediated by the protein NEDD8, is required for conformational changes of 
cullins, a scaffolding protein situated in the core of cullin-RING ligases, and 
regulation of E3 ligase activity. In this review, we present a comprehensive 
discussion of the recent findings on the neddylation pathway and its importance 
during tumorigenesis. The ramifications regarding the potential therapeutic use 
of ubiquination and neddylation inhibition are also discussed.