Neddylation is the writing of monomers or polymers of neural precursor cells expressed developmentally down-regulated 8 (NEDD8) to substrate. For neddylation to occur, three enzymes are required: activators (E1), conjugators (E2), and ligators (E3). However, the central role is played by the ubiquitin-conjugating enzymes E2M (UBE2M) and E2F (UBE2F), which are part of the E2 enzyme family. Recent understanding of the structure and mechanism of these two proteins provides insight into their physiological effects on apoptosis, cell cycle arrest and genome stability. To treat cancer, it is therefore appealing to develop novel inhibitors against UBE2M or UBE2F interactions with either E1 or E3. In this evaluation, we summarized the existing understanding of E2 interaction with E1 and E3 and reviewed the prospective of using neddylation E2 as a pharmacological target for evolving new anti-cancer remedies.

Neddylation 是将发育下调 8 (NEDD8) 表达的神经前体细胞的单体或多聚体写入底物。为了发生 neddylation，需要三种酶：激活剂 (E1)、接合剂 (E2) 和连接剂 (E3)。然而，发挥核心作用的是泛素结合酶 E2M (UBE2M) 和 E2F (UBE2F)，它们是 E2 酶家族的一部分。最近对这两种蛋白质的结构和机制的了解有助于深入了解它们对细胞凋亡、细胞周期停滞和基因组稳定性的生理影响。因此，为了治疗癌症，开发针对 UBE2M 或 UBE2F 与 E1 或 E3 相互作用的新型抑制剂非常有吸引力。在本次评估中，我们总结了对 E2 与 E1 和 E3 相互作用的现有理解，并回顾了使用 neddylation E2 作为开发新抗癌药物的药理学靶点的前景。