瞄准赖氨酸乙酰化的读者和作者

IF 122.7 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Ming-Ming Zhou, Philip A. Cole
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引用次数: 0

摘要

赖氨酸乙酰化是组蛋白和其他蛋白质的一种主要翻译后修饰,由 "写入 "赖氨酸乙酰转移酶(KATs)催化,并介导与溴化结构域(BrDs)和其他 "读取 "蛋白质的相互作用。KATs 和 BrDs 在调控基因表达、细胞生长、染色质结构和表观遗传学方面发挥着关键作用,在包括癌症在内的疾病状态中常常出现失调。为了开发新的治疗药物,人们一直在加速寻找能靶向单个 KATs 和 BrDs 的强效选择性小分子,其中一些药物已进入临床试验阶段。在此,我们总结了 KATs 和 BrDs 的不同家族,讨论了它们的功能和结构,并重点介绍了在设计和开发有望阻断这些染色质蛋白的作用以治疗疾病的化学制剂方面取得的主要进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Targeting lysine acetylation readers and writers

Targeting lysine acetylation readers and writers

Targeting lysine acetylation readers and writers
Lysine acetylation is a major post-translational modification in histones and other proteins that is catalysed by the ‘writer’ lysine acetyltransferases (KATs) and mediates interactions with bromodomains (BrDs) and other ‘reader’ proteins. KATs and BrDs play key roles in regulating gene expression, cell growth, chromatin structure, and epigenetics and are often dysregulated in disease states, including cancer. There have been accelerating efforts to identify potent and selective small molecules that can target individual KATs and BrDs with the goal of developing new therapeutics, and some of these agents are in clinical trials. Here, we summarize the different families of KATs and BrDs, discuss their functions and structures, and highlight key advances in the design and development of chemical agents that show promise in blocking the action of these chromatin proteins for disease treatment. Lysine acetylation is a post-translational modification on histones and other proteins that is catalysed by acetyltransferases (‘writers’) and mediates interactions with bromodomains and other ‘reader’ domains. This Review summarizes the properties and functions of these writers and readers and discusses efforts to identify small-molecule therapeutics that target them, some of which are being evaluated in clinical trials.
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来源期刊
Nature Reviews. Drug Discovery
Nature Reviews. Drug Discovery 医学-生物工程与应用微生物
CiteScore
137.40
自引率
0.30%
发文量
227
期刊介绍: Nature Reviews Drug Discovery is a monthly journal aimed at everyone working in the drug discovery and development arena. Each issue includes: Highest-quality reviews and perspectives covering a broad scope. News stories investigating the hottest topics in drug discovery. Timely summaries of key primary research papers. Concise updates on the latest advances in areas such as new drug approvals, patent law, and emerging industry trends and strategies.
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