Protein neddylation as a therapeutic target: challenges and opportunities.
review · Level V
Where this comes from
- Record sourced from PubMed, PMID 42544581.
- Also identified by DOI 10.1172/JCI206924 and PMC identifier 13430020.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Protein neddylation is an evolutionarily conserved posttranslational modification that conjugates NEDD8 to its substrate, catalyzed by an E1-activating enzyme, E2-conjugating enzyme, and E3 ligase. Neddylation is essential for cellular homeostasis, and its dysregulation has been implicated in diverse human diseases, including cancer, neurodegenerative diseases, and metabolic disorders, making the process a promising therapeutic target. In this Review, we systematically summarize the biochemical activity and biological functions of neddylation; its alterations in human diseases, particularly in cancers; and its validation as an attractive target for cancer therapy. We provide an overview on the discovery of neddylation inhibitors and the progress of MLN4924 (pevonedistat) and TAS4464 clinical trials and critically evaluate the core challenges and emerging opportunities for therapeutic strategies targeting neddylation.
Medical subject headings
- Protein Processing, Post-Translational
- Pyrimidines
- Ubiquitins
- Neoplasms
- Cyclopentanes