title: Targeting neddylation in cancer therapy.
abstract: 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.
authors.affiliation: International Center for Genetic Engineering & Biotechnology, Cancer Genomics Group, Werner & Beit Building South, Anzio road, UCT Campus, Cape Town 7925, South Africa.
authors.forename: Kristal
authors.initials: K
authors.lastname: Duncan
authors.forename: Georgia
authors.initials: G
authors.lastname: Schäfer
authors.forename: Akhona
authors.initials: A
authors.lastname: Vava
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Zerbini
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D044767:Ubiquitin-Protein Ligases