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 结合酶 E2 包括研究充分的泛素结合酶 E2 M (UBE2M) 和尚未充分表征的泛素结合酶 E2 F (UBE2F)。UBE2M 和 UBE2F 在催化 Cullin 或非 Cullin 底物的 neddylation 中具有独特而突出的作用。这些酶在各种恶性肿瘤中过度表达，导致总体存活率较差。通过调节肿瘤细胞的几种生物学反应（如 DNA 损伤反应、细胞凋亡或衰老）或调节抗肿瘤免疫来靶向 UBE2M 以影响肿瘤生长具有强大的治疗潜力。针对 UBE2M 和缺陷型库林 neddylation 蛋白 1 (DCN1)（一种用于 neddylation 的联合 E3）之间相互作用的多种抑制剂表现出有希望的抗肿瘤作用。相比之下，靶向 UBE2F 的潜在好处仍有待探索。目前报道抑制细胞凋亡，进而诱导细胞生长；因此，靶向 UBE2F 通过触发细胞凋亡作为一种有效的化学/放射增敏策略。这篇综述强调了 UBE2M 和 UBE2F 在肿瘤进展中的作用的最新进展，表明这些 E2 是两个有希望的抗肿瘤靶点。