赖氨酸乙酰转移酶抑制剂的生物学医学启示
KATs off: Biomedical insights from lysine acetyltransferase inhibitors.
机构信息
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
出版信息
Curr Opin Chem Biol. 2023 Feb;72:102255. doi: 10.1016/j.cbpa.2022.102255. Epub 2022 Dec 28.
Abstract
Lysine acetyltransferase (KAT) enzymes including the p300, MYST, and GCN5 families play major roles in modulating the structure of chromatin and regulating transcription. Because of their dysregulation in various disease states including cancer, efforts to develop inhibitors of KATs have steadily gained momentum. Here we provide an overview of recent progress on the development of high quality chemical probes of the p300 and MYST family of KATs and how they are emerging as useful tools for basic and translational investigation.
摘要
赖氨酸乙酰转移酶（KAT）酶包括 p300、MYST 和 GCN5 家族，在调节染色质结构和转录调控中发挥重要作用。由于它们在包括癌症在内的各种疾病状态中的失调，开发 KAT 抑制剂的努力一直在稳步推进。本文概述了开发 p300 和 MYST 家族 KAT 的高质量化学探针的最新进展，以及它们如何成为基础和转化研究的有用工具。
相似文献
1
KATs off: Biomedical insights from lysine acetyltransferase inhibitors.赖氨酸乙酰转移酶抑制剂的生物学医学启示
Curr Opin Chem Biol. 2023 Feb;72:102255. doi: 10.1016/j.cbpa.2022.102255. Epub 2022 Dec 28.
2
Genome-scale analysis of regulatory protein acetylation enzymes from photosynthetic eukaryotes.光合真核生物中调控蛋白乙酰化酶的全基因组规模分析。
BMC Genomics. 2017 Jul 5;18(1):514. doi: 10.1186/s12864-017-3894-0.
3
Profiling Cellular Substrates of Lysine Acetyltransferases GCN5 and p300 with Orthogonal Labeling and Click Chemistry.利用正交标记和点击化学技术分析赖氨酸乙酰转移酶GCN5和p300的细胞底物
ACS Chem Biol. 2017 Jun 16;12(6):1547-1555. doi: 10.1021/acschembio.7b00114. Epub 2017 Apr 26.
4
Identification of Novel Protein Lysine Acetyltransferases in Escherichia coli.大肠杆菌中新型蛋白质赖氨酸乙酰转移酶的鉴定
mBio. 2018 Oct 23;9(5):e01905-18. doi: 10.1128/mBio.01905-18.
5
Quantitative Acetylomics Reveals Substrates of Lysine Acetyltransferase GCN5 in Adult and Aging .定量乙酰化组学揭示赖氨酸乙酰转移酶 GCN5 在成年和衰老中的作用底物。
J Proteome Res. 2023 Sep 1;22(9):2909-2924. doi: 10.1021/acs.jproteome.3c00247. Epub 2023 Aug 6.
6
Lysine Acetyltransferases and Their Role in AR Signaling and Prostate Cancer.赖氨酸乙酰转移酶及其在 AR 信号转导和前列腺癌中的作用。
Front Endocrinol (Lausanne). 2022 Aug 17;13:886594. doi: 10.3389/fendo.2022.886594. eCollection 2022.
7
Characterization and prediction of lysine (K)-acetyl-transferase specific acetylation sites.赖氨酸（K）-乙酰转移酶特异性乙酰化位点的鉴定和预测。
Mol Cell Proteomics. 2012 Jan;11(1):M111.011080. doi: 10.1074/mcp.M111.011080. Epub 2011 Sep 30.
8
Chemical Biology Approaches for Investigating the Functions of Lysine Acetyltransferases.化学生物学方法研究赖氨酸乙酰转移酶的功能。
Angew Chem Int Ed Engl. 2018 Jan 26;57(5):1162-1184. doi: 10.1002/anie.201704745. Epub 2017 Dec 27.
9
Microfluidic Mobility Shift Profiling of Lysine Acetyltransferases Enables Screening and Mechanistic Analysis of Cellular Acetylation Inhibitors.赖氨酸乙酰转移酶的微流控迁移率变动分析可用于细胞乙酰化抑制剂的筛选和机制分析。
ACS Chem Biol. 2016 Mar 18;11(3):734-41. doi: 10.1021/acschembio.5b00709. Epub 2015 Oct 14.
10
Roles for lysine acetyltransferases during mammalian hibernation.赖氨酸乙酰转移酶在哺乳动物冬眠过程中的作用。
J Therm Biol. 2018 May;74:71-76. doi: 10.1016/j.jtherbio.2018.03.013. Epub 2018 Mar 15.
引用本文的文献
1
Structural and functional characterization of CREB-binding protein (CREBBP) as a histone propionyltransferase.作为组蛋白丙酰转移酶的CREB结合蛋白（CREBBP）的结构与功能特性
J Biol Chem. 2025 Jul 2;301(8):110444. doi: 10.1016/j.jbc.2025.110444.
2
NAA10 (N-Alpha-Acetyltransferase 10): A Multifunctional Regulator in Development, Disease, and Cancer.NAA10（N-α-乙酰基转移酶10）：发育、疾病和癌症中的多功能调节因子。
Cells. 2025 Jun 7;14(12):863. doi: 10.3390/cells14120863.
3
Development of p300-targeting degraders with enhanced selectivity and onset of degradation.具有增强选择性和降解起始效果的p300靶向降解剂的开发。
RSC Med Chem. 2025 Mar 3;16(5):2049-2060. doi: 10.1039/d4md00969j. eCollection 2025 May 22.
4
Acetylation: a new target for protein degradation in cancer.乙酰化：癌症中蛋白质降解的新靶点。
Trends Cancer. 2025 Apr;11(4):403-420. doi: 10.1016/j.trecan.2025.01.013. Epub 2025 Mar 6.
5
Modulation of the substrate preference of a MYST acetyltransferase by a scaffold protein.支架蛋白对MYST乙酰转移酶底物偏好性的调控
J Biol Chem. 2025 Mar;301(3):108262. doi: 10.1016/j.jbc.2025.108262. Epub 2025 Feb 3.
6
Targeting lysine acetylation readers and writers.靶向赖氨酸乙酰化的识别蛋白和写入蛋白。
Nat Rev Drug Discov. 2025 Feb;24(2):112-133. doi: 10.1038/s41573-024-01080-6. Epub 2024 Nov 21.
7
Paralogue-Selective Degradation of the Lysine Acetyltransferase EP300.赖氨酸乙酰转移酶EP300的旁系同源物选择性降解
JACS Au. 2024 Jul 29;4(8):3094-3103. doi: 10.1021/jacsau.4c00442. eCollection 2024 Aug 26.
8
Evaluating the Cellular Roles of the Lysine Acetyltransferase Tip60 in Cancer: A Multi-Action Molecular Target for Precision Oncology.评估赖氨酸乙酰转移酶Tip60在癌症中的细胞作用：精准肿瘤学的多作用分子靶点
Cancers (Basel). 2024 Jul 27;16(15):2677. doi: 10.3390/cancers16152677.
9
The role of acetylation in obesity-induced cardiac metabolic alterations.乙酰化在肥胖诱导的心脏代谢改变中的作用。
J Pharm Pharm Sci. 2024 Jul 23;27:13080. doi: 10.3389/jpps.2024.13080. eCollection 2024.
10
Paralogue-selective degradation of the lysine acetyltransferase EP300.赖氨酸乙酰转移酶EP300的旁系同源物选择性降解
bioRxiv. 2024 May 5:2024.05.03.592353. doi: 10.1101/2024.05.03.592353.
本文引用的文献
1
Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes.组蛋白 H2B 的乙酰化标记活跃的增强子，并预测 CBP/p300 的靶基因。
Nat Genet. 2023 Apr;55(4):679-692. doi: 10.1038/s41588-023-01348-4. Epub 2023 Apr 6.
2
Targeting cell cycle and apoptosis to overcome chemotherapy resistance in acute myeloid leukemia.靶向细胞周期和凋亡以克服急性髓系白血病的化疗耐药性。
Leukemia. 2023 Jan;37(1):143-153. doi: 10.1038/s41375-022-01755-2. Epub 2022 Nov 18.
3
Structure of the NuA4 acetyltransferase complex bound to the nucleosome.NuA4 乙酰转移酶复合物与核小体结合的结构。
Nature. 2022 Oct;610(7932):569-574. doi: 10.1038/s41586-022-05303-x. Epub 2022 Oct 5.
4
The p300 Inhibitor A-485 Exerts Antitumor Activity in Growth Hormone Pituitary Adenoma.p300 抑制剂 A-485 在生长激素垂体腺瘤中发挥抗肿瘤活性。
J Clin Endocrinol Metab. 2022 May 17;107(6):e2291-e2300. doi: 10.1210/clinem/dgac128.
5
RBBP4-p300 axis modulates expression of genes essential for cell survival and is a potential target for therapy in glioblastoma.RBBP4-p300 轴调节细胞存活所必需的基因的表达，是胶质母细胞瘤治疗的潜在靶点。
Neuro Oncol. 2022 Aug 1;24(8):1261-1272. doi: 10.1093/neuonc/noac051.
6
Histone H2B Deacylation Selectivity: Exploring Chromatin's Dark Matter with an Engineered Sortase.组蛋白 H2B 去乙酰化选择性：用工程化的 sortase 探索染色质的暗物质。
J Am Chem Soc. 2022 Mar 2;144(8):3360-3364. doi: 10.1021/jacs.1c13555. Epub 2022 Feb 17.
7
YEATS Domains as Novel Epigenetic Readers: Structures, Functions, and Inhibitor Development.叶茨结构域作为新型表观遗传读码器：结构、功能及抑制剂开发。
ACS Chem Biol. 2023 Apr 21;18(4):994-1013. doi: 10.1021/acschembio.1c00945. Epub 2022 Jan 18.
8
Design, synthesis and biological evaluation of a novel spiro oxazolidinedione as potent p300/CBP HAT inhibitor for the treatment of ovarian cancer.新型螺环噁唑烷二酮类 p300/CBP HAT 抑制剂的设计、合成与生物评价及其在卵巢癌治疗中的应用。
Bioorg Med Chem. 2021 Dec 15;52:116512. doi: 10.1016/j.bmc.2021.116512. Epub 2021 Nov 10.
9
EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified Neuroblastoma.EP300 选择性控制 MYCN 扩增神经母细胞瘤的增强子景观。
Cancer Discov. 2022 Mar 1;12(3):730-751. doi: 10.1158/2159-8290.CD-21-0385.
10
Inactivation of the CIC-DUX4 oncogene through P300/CBP inhibition, a therapeutic approach for CIC-DUX4 sarcoma.通过抑制P300/CBP使CIC-DUX4致癌基因失活，一种治疗CIC-DUX4肉瘤的方法。
Oncogenesis. 2021 Oct 12;10(10):68. doi: 10.1038/s41389-021-00357-4.
Zotero 插件