State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu (Y.Ya., Z.X., X.W., X.Z., Z.S., Y.Ye., G.H., L.Z., N.X., S.L.); Departments of Nephrology (Z.X.) and Neurosurgery (L.Z.), West China Hospital, Sichuan University, Chengdu; and Laboratory of Cell and Molecular Biology, and State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences, Beijing (H.Z., N.X.), People's Republic of China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu (Y.Ya., Z.X., X.W., X.Z., Z.S., Y.Ye., G.H., L.Z., N.X., S.L.); Departments of Nephrology (Z.X.) and Neurosurgery (L.Z.), West China Hospital, Sichuan University, Chengdu; and Laboratory of Cell and Molecular Biology, and State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences, Beijing (H.Z., N.X.), People's Republic of China
Mol Pharmacol. 2018 Aug;94(2):885-894. doi: 10.1124/mol.118.112300. Epub 2018 May 21.
SUMOylation, one of post-translational modifications, is covalently modified on lysine residues of a target protein through an enzymatic cascade reaction similar to protein ubiquitination. Along with identification of many SUMOylated proteins, protein SUMOylation has been proven to regulate multiple biologic activities including transcription, cell cycle, DNA repair, and innate immunity. The dysregulation of protein SUMOylation and deSUMOylation modification is linked with carcinogenesis and tumor progression. The SUMOylation-associated enzymes are usually elevated in various cancers, which function as cancer biomarkers to relate to poor outcomes for patients. Considering the significance of protein SUMOylation in regulating diverse biologic functions in cancer progression, numerous small-molecule inhibitors targeting protein SUMOylation pathway are developed as potentially clinical anticancer therapeutics. Here, we systematically summarize the latest progresses of associations of small ubiquitin-like modifier (SUMO) enzymes with cancers and small-molecular inhibitors against human cancers by targeting SUMOylation enzymes. We also compared the pros and cons of several special anticancer inhibitors targeting SUMO pathway. As more efforts are invested in this field, small-molecule inhibitors targeting the SUMOylation modification pathway are promising for development into novel anticancer drugs.
SUMOylation 是一种翻译后修饰，通过类似于蛋白质泛素化的酶级联反应，在靶蛋白的赖氨酸残基上共价修饰。随着许多 SUMOylated 蛋白质的鉴定，蛋白质 SUMOylation 已被证明调节多种生物活性，包括转录、细胞周期、DNA 修复和先天免疫。蛋白质 SUMOylation 和去 SUMOylation 修饰的失调与癌症发生和肿瘤进展有关。SUMOylation 相关酶通常在各种癌症中升高，它们作为癌症生物标志物与患者预后不良相关。鉴于蛋白质 SUMOylation 在调节癌症进展中多种生物功能的重要性，针对蛋白质 SUMOylation 途径的许多小分子抑制剂被开发为潜在的临床抗癌治疗药物。在这里，我们系统地总结了小分子泛素样修饰物（SUMO）酶与癌症的最新关联，以及针对 SUMOylation 酶的小分子抑制剂对人类癌症的作用。我们还比较了几种针对 SUMO 通路的特殊抗癌抑制剂的优缺点。随着在该领域投入更多的努力，针对 SUMOylation 修饰途径的小分子抑制剂有望开发成为新型抗癌药物。
