当期文章

蛋白质琥珀酸化修饰在癌症中的研究进展

鞠前前, 孙诚^*

国家药品监督管理局组织工程技术产品研究与评价重点实验室，教育部神经再生重点实验室，江苏省组织工程与神经再生重点实验室，神经再生协同创新中心，南通大学神经再生重点实验室，南通 226001

摘要

代谢异常是癌症的显著特征之一。编码三羧酸(tricarboxylic acid, TCA)循环关键代谢酶的基因突变可导致“致癌代谢物”的积累。这些代谢物通过抑制酶活性或驱动蛋白质共价修饰，在肿瘤发生、发展及免疫反应中发挥重要作用。延胡索酸因TCA循环紊乱或延胡索酸水合酶(fumarate hydratase, FH)失活突变而积累，影响线粒体功能、DNA损伤修复、蛋白质功能及肿瘤微环境。作为一种α,β-不饱和亲电子代谢物，延胡索酸通过迈克尔加成反应与蛋白质半胱氨酸残基形成稳定的S-(2-琥珀酸)半胱氨酸[S-(2-succinyl)cysteine, 2SC]修饰，这一翻译后修饰过程被称为蛋白质琥珀酸化修饰。研究表明，蛋白质琥珀酸化修饰在肿瘤发生、发展及免疫逃逸中发挥关键作用，其研究结果为肿瘤诊疗提供了新视角。未来，基于蛋白质琥珀酸化修饰的代谢干预策略有望显著改善肿瘤治疗效果。本综述系统总结了蛋白质琥珀酸化修饰在肿瘤代谢和免疫逃逸中的作用及其潜在的临床应用价值。

关键词： 延胡索酸; 琥珀酸化修饰; S-(2-琥珀酸)半胱氨酸; 延胡索酸水合酶; 半胱氨酸; 生物标志物

Research progress on protein succination modification in cancer

JU Qian-Qian, SUN Cheng^*

NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Key Laboratory of Neuroregeneration of Ministry of Education, Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Co-innovation Center of Neuroregeneration, Key Laboratory of Neuroregeneration of Nantong University, Nantong 226001, China

Abstract

Metabolic dysregulation is a hallmark of cancer. Mutations in genes encoding key enzymes of the tricarboxylic acid (TCA) cycle can result in the accumulation of "oncometabolites". These metabolites play essential roles in tumor initiation, progression, and immune evasion by inhibiting enzymatic activity or driving covalent protein modifications. Accumulation of fumarate due to TCA cycle disruptions or fumarate hydratase (FH) inactivation mutation affects mitochondrial function, DNA repair, protein function, and the tumor microenvironment. As an α,β-unsaturated electrophilic metabolite, fumarate reacts with cysteine residues on susceptible proteins via Michael addition, generating stable S-(2-succinyl)cysteine (2SC) modifications, a post-translational modification process known as protein succination modification. Research has shown that protein succination modification plays a critical role in tumor initiation, progression, and immune evasion, providing new insights for cancer diagnosis and therapy. Future metabolic interventions targeting succination modification could significantly improve cancer therapies. This review offers a comprehensive overview of the role of protein succination modification in tumor metabolism and immune evasion, along with its potential clinical applications.

Key words: fumarate; succination modification; S-(2-succinyl)cysteine; fumarate hydratase; cysteine; biomarker

收稿日期：　　录用日期：

通讯作者：孙诚　　E-mail:

DOI: 10.13294/j.aps.2026.0036

引用本文：

鞠前前, 孙诚. 蛋白质琥珀酸化修饰在癌症中的研究进展[J]. 生理学报 2026; 78 (2): 331-341.

JU Qian-Qian, SUN Cheng. Research progress on protein succination modification in cancer. Acta Physiol Sin 2026; 78 (2): 331-341 (in Chinese with English abstract).