Gao Jie, Yu Wei
Institute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.
Cancers (Basel). 2025 Aug 14;17(16):2652. doi: 10.3390/cancers17162652.
Lysine succinylation is a recently discovered post-translational protein modification, the process of which requires the participation of various enzymes. The close association between cancer and protein post-translational modifications (PTMs), such as acetylation and phosphorylation, has been extensively investigated and well-established. In recent years, growing attention has been directed toward the role of succinylation in cancer progression. Accumulating evidence demonstrates that protein succinylation and desuccinylation play critical roles in promoting the development of various cancers, including lung, prostate, and renal cancers. Notably, the primary substrates undergoing succinylation are non-histone proteins. Therefore, elucidating the functions of cancer-related succinylated proteins is essential for identifying novel therapeutic targets. This review comprehensively summarizes current research advances regarding protein succinylation in common cancers and discusses the progress in developing succinylation-targeting drugs. Specifically, we focus on the molecular mechanisms by which succinylation regulates cancer progression, along with the identification of key succinylation sites. Our discussion aims to provide valuable insights for future research and the development of innovative cancer treatments.
赖氨酸琥珀酰化是一种最近发现的蛋白质翻译后修饰,其过程需要多种酶的参与。癌症与蛋白质翻译后修饰(如乙酰化和磷酸化)之间的密切关联已得到广泛研究并被充分证实。近年来,琥珀酰化在癌症进展中的作用受到越来越多的关注。越来越多的证据表明,蛋白质琥珀酰化和去琥珀酰化在促进包括肺癌、前列腺癌和肾癌在内的各种癌症的发展中起着关键作用。值得注意的是,发生琥珀酰化的主要底物是非组蛋白。因此,阐明癌症相关琥珀酰化蛋白的功能对于确定新的治疗靶点至关重要。本综述全面总结了常见癌症中蛋白质琥珀酰化的当前研究进展,并讨论了开发靶向琥珀酰化药物的进展。具体而言,我们关注琥珀酰化调节癌症进展的分子机制以及关键琥珀酰化位点的鉴定。我们的讨论旨在为未来的研究和创新癌症治疗的开发提供有价值的见解。