NEDD8-conjugating enzyme E2s: critical targets for cancer therapy

• Published in: Cell death discovery Vol. 9; no. 1; p. 23
• Main Authors: Zhou, Lisha, Lin, Xiongzhi, Zhu, Jin, Zhang, Luyi, Chen, Siyuan, Yang, Hui, Jia, Lijun, Chen, Baofu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-01-2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/67/395; 631/67/580; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cancer therapies; Cell Biology; Cell Cycle Analysis; Cullin; DNA damage; Enzymes; Life Sciences; Malignancy; Review; Review Article; Senescence; Stem Cells; Tumor cells; Ubiquitin; Ubiquitin-conjugating enzyme; Ubiquitin-protein ligase
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-023-01337-w

NEDD8-conjugating enzymes, E2s, include the well-studied ubiquitin-conjugating enzyme E2 M (UBE2M) and the poorly characterized ubiquitin-conjugating enzyme E2 F (UBE2F). UBE2M and UBE2F have distinct and prominent roles in catalyzing the neddylation of Cullin or non-Cullin substrates. These enzymes are overexpressed in various malignancies, conferring a worse overall survival. Targeting UBE2M to influence tumor growth by either modulating several biological responses of tumor cells (such as DNA-damage response, apoptosis, or senescence) or regulating the anti-tumor immunity holds strong therapeutic potential. Multiple inhibitors that target the interaction between UBE2M and defective cullin neddylation protein 1 (DCN1), a co-E3 for neddylation, exhibit promising anti-tumor effects. By contrast, the potential benefits of targeting UBE2F are still to be explored. It is currently reported to inhibit apoptosis and then induce cell growth; hence, targeting UBE2F serves as an effective chemo-/radiosensitizing strategy by triggering apoptosis. This review highlights the most recent advances in the roles of UBE2M and UBE2F in tumor progression, indicating these E2s as two promising anti-tumor targets.