发现具有治疗活性的neddylation E2酶抑制剂。
Discovery of neddylation E2s inhibitors with therapeutic activity.
发表日期：2023 Sep 16
作者：
Maa Mamun, Ying Liu, Yin-Ping Geng, Yi-Chao Zheng, Ya Gao, Jian-Gang Sun, Long-Fei Zhao, Li-Juan Zhao, Hong-Min Liu
来源：
Oncogenesis
摘要：
神经前体细胞发育下调8号基因（NEDD8）的单体或聚合物被编写到底物中称为泛素样蛋白化修饰。为了进行泛素样蛋白化修饰，需要三种酶：激活酶（E1）、结合酶（E2）和连接酶（E3）。然而，泛素连接酶酶E2M（UBE2M）和E2F（UBE2F）在其中扮演着核心角色，它们是E2酶家族的一部分。对这两种蛋白质的结构和机制的最新了解揭示了它们在细胞凋亡、细胞周期阻滞和基因组稳定性方面的生理效应。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非常具有吸引力。在这个评估中，我们总结了E2与E1和E3的现有理解，并总结了将泛素样蛋白化修饰酶E2作为药理学靶点用于开发新型抗癌疗法的前景。© 2023. Springer Nature America, Inc.
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.© 2023. Springer Nature America, Inc.