School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China.
School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Pharmacol Res. 2021 Aug;170:105493. doi: 10.1016/j.phrs.2021.105493. Epub 2021 Feb 15.
Gastric carcinoma has serious morbidity and mortality, which seriously threats human health. The studies on gastrointestinal cell biology have shown that the ubiquitination modification that occurs after protein translation plays an essential role in the pathogenesis of gastric carcinoma. Protein ubiquitination is catalyzed by E3 ubiquitin ligase and can regulate various substrate proteins in different cellular pathways. Cullin-RING E3 ligase (CRLs) is a representative of the E3 ubiquitin ligase family, which requires cullin (CUL) neddylation modification for activation to regulate homeostasis of ~20% of cellular proteins. The substrate molecules regulated by CRLs are often involved in many cell progressions such as cell cycle progression, cell apoptosis, DNA damage and repair. Given that CRLs play an important role in modulation of biological activities, so targeting a certain CULs member neddylation may be an attractive strategy for selectively controlling the cellular proteins levels to achieve the goal of cancer treatment. In this review, we will discuss the roles of CULs and Ring protein in gastric carcinoma and summarize the current neddylation modulators for gastric carcinoma treatment.
胃癌具有严重的发病率和死亡率，严重威胁着人类的健康。胃肠道细胞生物学的研究表明，蛋白质翻译后发生的泛素化修饰在胃癌的发病机制中起着至关重要的作用。蛋白质泛素化是由 E3 泛素连接酶催化的，可以调节不同细胞途径中的各种底物蛋白。Cullin-RING E3 连接酶（CRLs）是 E3 泛素连接酶家族的代表，它需要 cullin（CUL）的 neddylation 修饰来激活，以调节约 20%的细胞蛋白的内稳态。CRLs 调节的底物分子通常涉及许多细胞进程，如细胞周期进程、细胞凋亡、DNA 损伤和修复。鉴于 CRLs 在调节生物活性方面发挥着重要作用，因此靶向特定的 CULs 成员的 neddylation 可能是一种有吸引力的策略，可用于选择性控制细胞蛋白水平，以实现癌症治疗的目标。在这篇综述中，我们将讨论 CULs 和 Ring 蛋白在胃癌中的作用，并总结目前用于胃癌治疗的 neddylation 调节剂。
