Zhou Lisha, Lin Xiongzhi, Zhu Jin, Zhang Luyi, Chen Siyuan, Yang Hui, Jia Lijun, Chen Baofu
Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang, China.
Graduate School of Medicine, Hebei North University, Zhangjiakou, Hebei, China.
Cell Death Discov. 2023 Jan 23;9(1):23. 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.
NEDD8缀合酶（E2）包括研究充分的泛素缀合酶E2 M（UBE2M）和特征描述较少的泛素缀合酶E2 F（UBE2F）。UBE2M和UBE2F在催化Cullin或非Cullin底物的NEDD化过程中具有独特且显著的作用。这些酶在多种恶性肿瘤中过度表达，导致总体生存率较差。靶向UBE2M以通过调节肿瘤细胞的多种生物学反应（如DNA损伤反应、凋亡或衰老）或调节抗肿瘤免疫来影响肿瘤生长具有强大的治疗潜力。多种靶向UBE2M与缺陷型Cullin NEDD化蛋白1（DCN1，一种NEDD化的共E3）之间相互作用的抑制剂显示出有前景的抗肿瘤效果。相比之下，靶向UBE2F的潜在益处仍有待探索。目前报道它可抑制凋亡进而诱导细胞生长；因此，靶向UBE2F通过触发凋亡可作为一种有效的化疗/放疗增敏策略。本综述重点介绍了UBE2M和UBE2F在肿瘤进展中的作用的最新进展，表明这些E2是两个有前景的抗肿瘤靶点。
