Targeting neddylation in cancer therapy

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.