Short‐chain acyl post‐translational modifications in cancers: Mechanisms, roles, and therapeutic implications

作者：Ting Wu, Ying‐Qi Zhao, Xinming Zhang, Yuanhe Wang, Qiuchen Chen, Ming‐Rong Zhang, Huan Sheng, Yuying Zhang, Jinyu Guo, Jun Li, Yuxuan Fan, Ziqing Wang, Yalun Li, Haoran Wang, Minjie Wei, Xiaoyun Hu, Huizhe Wu · 发表于：癌症：英文版 · 年份：2025 · DOI：10.1002/cac2.70048 · 被引用次数：44 · 研究领域：Histone Deacetylase Inhibitors Research、Ubiquitin and proteasome pathways、Peptidase Inhibition and Analysis

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation, and lactylation, differing from traditional acetylation in structure, physicochemical properties, function, and regulation. Aberrant short-chain acyl-PTMs are often associated with tumorigenesis. Research highlights that PTMs like succinylation and lactylation are essential in regulating tumor metabolism, drug resistance, and immune responses. This review elucidates the regulatory mechanisms of eight short-chain acyl-PTMs-butyrylation, succinylation, crotonylation, malonylation, glutarylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, and lactylation-that are involved in tumor initiation and progression. Their roles in controlling tumor genomic stability, gene transcription, protein stability, enzyme activity, and nuclear localization are summarized, demonstrating their impact on related biological processes such as tumor metabolism, multi-drug resistance, and immune evasion. Ad...