Protein acylation: mechanisms, biological functions and therapeutic targets.

Protein acylation: mechanisms, biological functions and therapeutic targets.
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蛋白质酰化:机制、生物学功能和治疗靶点

DOI:
10.1038/s41392-022-01245-y
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发表时间:
2022-12-29
影响因子:
39.3
通讯作者:
Hua, Fang
Hua, Fang
中科院分区:
医学1区
文献类型:
--
作者:
Shang, Shuang;Liu, Jing;Hua, Fang

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代谢重编程不仅参与癌症的发病机制,而且参与神经退行性疾病、心血管疾病和传染病的发病机制。随着代谢组学和蛋白质组学的发展,发现代谢物通过提供酰基或改变酰基转移酶或脱酰基酶的活性来影响蛋白质的酰化。反过来,蛋白质酰化参与与生理学和疾病相关的关键细胞过程,例如蛋白质稳定性、蛋白质亚细胞定位、酶活性、转录活性、蛋白质-蛋白质相互作用和蛋白质-DNA相互作用。本文综述了8种非组蛋白酰化在多种疾病生理过程和进展中的功能多样性及其作用机制。我们还强调了酰基转移酶、脱酰酶和酰化阅读蛋白抑制剂开发的最新进展,以探讨其在药物发现中的潜在应用。
Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular diseases, and infectious diseases. With the progress of metabonomics and proteomics, metabolites have been found to affect protein acylations through providing acyl groups or changing the activities of acyltransferases or deacylases. Reciprocally, protein acylation is involved in key cellular processes relevant to physiology and diseases, such as protein stability, protein subcellular localization, enzyme activity, transcriptional activity, protein–protein interactions and protein–DNA interactions. Herein, we summarize the functional diversity and mechanisms of eight kinds of nonhistone protein acylations in the physiological processes and progression of several diseases. We also highlight the recent progress in the development of inhibitors for acyltransferase, deacylase, and acylation reader proteins for their potential applications in drug discovery.
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