Mamun Maa, Liu Ying, Geng Yin-Ping, Zheng Yi-Chao, Gao Ya, Sun Jian-Gang, Zhao Long-Fei, Zhao Li-Juan, Liu Hong-Min
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment; Key Laboratory of Henan Province for Drug Quality and Evaluation; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China.
Henan Engineering Research Center for Application & Translation of Precision Clinical Pharmacy; Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Oncogenesis. 2023 Sep 16;12(1):45. doi: 10.1038/s41389-023-00490-2.
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是指将神经前体细胞中发育性下调的8（NEDD8）单体或聚合物连接到底物上的过程。Neddylation的发生需要三种酶：激活酶（E1）、结合酶（E2）和连接酶（E3）。然而，泛素结合酶E2M（UBE2M）和E2F（UBE2F）起着核心作用，它们属于E2酶家族。最近对这两种蛋白质结构和机制的了解为深入了解它们对细胞凋亡、细胞周期阻滞和基因组稳定性的生理影响提供了线索。因此，开发针对UBE2M或UBE2F与E1或E3相互作用的新型抑制剂来治疗癌症具有吸引力。在本评估中，我们总结了目前对E2与E1和E3相互作用的认识，并综述了将Neddylation E2作为开发新型抗癌药物的药理学靶点的前景。
