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

IF 24.9 1区 医学 Q1 ONCOLOGY
Ting Wu, Yingqi Zhao, Xin Zhang, Yuanhe Wang, Qiuchen Chen, Mingrong Zhang, Huan Sheng, Yuying Zhang, Jinyu Guo, Jun Li, Yuxuan Fan, Ziqing Wang, Yalun Li, Haoran Wang, Minjie Wei, Xiaoyun Hu, Huizhe Wu
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Abstract

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. Additionally, the review provides an overview of current drug research targeting enzymes that regulate PTMs, offering critical insights to advance therapeutic strategies for cancer treatment.

Abstract Image

癌症中的短链酰基翻译后修饰:机制、作用和治疗意义。
翻译后修饰(PTMs)在表观遗传调控中起着关键作用,是调节蛋白质功能的关键途径。PTMs涉及不同的化学基团(如琥珀基、巴豆基和丙基)在特定蛋白质位点上的共价附着,从而改变蛋白质的结构、功能、稳定性和活性,最终影响生物过程。最近,代谢衍生的短链酰化修饰(酰基含有少于6个碳原子)已逐渐被发现,如丁基化、琥珀酰化、巴豆酰化和乳酸化,它们在结构、理化性质、功能和调控方面与传统的乙酰化有所不同。异常的短链酰基- ptms常与肿瘤发生有关。研究强调,琥珀酰化和乳酸酰化等PTMs在调节肿瘤代谢、耐药和免疫反应中至关重要。本文综述了八种短链酰基- ptms -丁基化、琥珀酰化、巴豆酰化、丙二烯酰化、戊二酰化、2-羟基异丁基化、β-羟基丁基化和乳酸化参与肿瘤发生和发展的调控机制。综述了它们在控制肿瘤基因组稳定性、基因转录、蛋白质稳定性、酶活性和核定位等方面的作用,展示了它们对肿瘤代谢、多药耐药和免疫逃避等相关生物学过程的影响。此外,该综述还概述了目前针对调节PTMs的酶的药物研究,为推进癌症治疗策略提供了重要见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Communications
Cancer Communications Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
25.50
自引率
4.30%
发文量
153
审稿时长
4 weeks
期刊介绍: Cancer Communications is an open access, peer-reviewed online journal that encompasses basic, clinical, and translational cancer research. The journal welcomes submissions concerning clinical trials, epidemiology, molecular and cellular biology, and genetics.
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