Suppr超能文献

表观遗传学及其他:以蛋白质赖氨酸甲基化写作者为靶点治疗疾病。

Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease.

机构信息

Department of Biology, Stanford University, Stanford, CA, USA.

Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Nat Rev Drug Discov. 2021 Apr;20(4):265-286. doi: 10.1038/s41573-020-00108-x. Epub 2021 Jan 19.

Abstract

Protein lysine methylation is a crucial post-translational modification that regulates the functions of both histone and non-histone proteins. Deregulation of the enzymes or 'writers' of protein lysine methylation, lysine methyltransferases (KMTs), is implicated in the cause of many diseases, including cancer, mental health disorders and developmental disorders. Over the past decade, significant advances have been made in developing drugs to target KMTs that are involved in histone methylation and epigenetic regulation. The first of these inhibitors, tazemetostat, was recently approved for the treatment of epithelioid sarcoma and follicular lymphoma, and several more are in clinical and preclinical evaluation. Beyond chromatin, the many KMTs that regulate protein synthesis and other fundamental biological processes are emerging as promising new targets for drug development to treat diverse diseases.

摘要

蛋白质赖氨酸甲基化是一种至关重要的翻译后修饰,它调节组蛋白和非组蛋白的功能。蛋白质赖氨酸甲基转移酶(KMTs)的酶或“书写器”的失调与许多疾病的病因有关,包括癌症、精神健康障碍和发育障碍。在过去的十年中,在开发针对涉及组蛋白甲基化和表观遗传调控的 KMT 的药物方面取得了重大进展。这些抑制剂中的第一个,塔美塞他,最近被批准用于治疗上皮样肉瘤和滤泡性淋巴瘤,还有更多的正在临床和临床前评估中。除了染色质之外,许多调节蛋白质合成和其他基本生物过程的 KMT 正在成为治疗各种疾病的药物开发的有前途的新靶点。

相似文献

2
Chemical biology and pharmacology of histone lysine methylation inhibitors.组蛋白赖氨酸甲基化抑制剂的化学生物学和药理学。
Biochim Biophys Acta Gene Regul Mech. 2022 Aug;1865(6):194840. doi: 10.1016/j.bbagrm.2022.194840. Epub 2022 Jun 24.
3
Emerging roles of lysine methylation on non-histone proteins.赖氨酸甲基化在非组蛋白上的新作用。
Cell Mol Life Sci. 2015 Nov;72(22):4257-72. doi: 10.1007/s00018-015-2001-4. Epub 2015 Jul 31.
4
Targeting histone lysine methylation in cancer.靶向癌症中的组蛋白赖氨酸甲基化。
Pharmacol Ther. 2015 Jun;150:1-22. doi: 10.1016/j.pharmthera.2015.01.002. Epub 2015 Jan 9.
5
Lysine methylation: Implications in neurodegenerative disease.赖氨酸甲基化:在神经退行性疾病中的意义。
Brain Res. 2019 Mar 15;1707:164-171. doi: 10.1016/j.brainres.2018.11.024. Epub 2018 Nov 19.
8
9
An unexpected journey: lysine methylation across the proteome.一段意外之旅:蛋白质组中的赖氨酸甲基化
Biochim Biophys Acta. 2014 Dec;1839(12):1395-403. doi: 10.1016/j.bbagrm.2014.02.008. Epub 2014 Feb 20.

引用本文的文献

4
The role of ubiquitination and deubiquitination in urological tumours.泛素化和去泛素化在泌尿系统肿瘤中的作用。
Front Pharmacol. 2025 Jul 23;16:1532878. doi: 10.3389/fphar.2025.1532878. eCollection 2025.

本文引用的文献

6
Epigenetic Therapy for Epithelioid Sarcoma.上皮样肉瘤的表观遗传学治疗。
Cell. 2020 Apr 16;181(2):211. doi: 10.1016/j.cell.2020.03.042.
8
H2A.Z facilitates licensing and activation of early replication origins.H2A.Z 促进早期复制起始点的许可和激活。
Nature. 2020 Jan;577(7791):576-581. doi: 10.1038/s41586-019-1877-9. Epub 2019 Dec 25.
9
Discovery of a chemical probe for PRDM9.发现 PRDM9 的化学探针。
Nat Commun. 2019 Dec 17;10(1):5759. doi: 10.1038/s41467-019-13652-x.
10
Discovery of a first-in-class EZH2 selective degrader.发现首个 EZH2 选择性降解剂。
Nat Chem Biol. 2020 Feb;16(2):214-222. doi: 10.1038/s41589-019-0421-4. Epub 2019 Dec 9.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验