• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

BET蛋白的生物化学、生理学及病理作用综述

A Comprehensive Review of BET Protein Biochemistry, Physiology, and Pathological Roles.

作者信息

Ali Hafiz Akbar, Li Yalan, Bilal Akram Hafiz Muhammad, Qin Tingting, Yuan Ziqiao, Zhao Wen

机构信息

Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

出版信息

Front Pharmacol. 2022 Mar 25;13:818891. doi: 10.3389/fphar.2022.818891. eCollection 2022.

DOI:10.3389/fphar.2022.818891
PMID:35401196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8990909/
Abstract

Epigenetic modifications, specifically acetylation of histone plays a decisive role in gene regulation and transcription of normal cellular mechanisms and pathological conditions. The bromodomain and extraterminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT), being epigenetic readers, ligate to acetylated regions of histone and synchronize gene transcription. BET proteins are crucial for normal cellular processing as they control cell cycle progression, neurogenesis, differentiation, and maturation of erythroids and spermatogenesis, etc. Research-based evidence indicated that BET proteins (mainly BRD4) are associated with numeral pathological ailments, including cancer, inflammation, infections, renal diseases, and cardiac diseases. To counter the BET protein-related pathological conditions, there are some BET inhibitors developed and also under development. BET proteins are a topic of most research nowadays. This review, provides an ephemeral but comprehensive knowledge about BET proteins' basic structure, biochemistry, physiological roles, and pathological conditions in which the role of BETs have been proven. This review also highlights the current and future approaches to pledge BET protein-related pathologies.

摘要

表观遗传修饰，特别是组蛋白乙酰化，在正常细胞机制和病理状态的基因调控及转录中起决定性作用。含溴结构域和额外末端（BET）蛋白（BRD2、BRD3、BRD4和BRDT）作为表观遗传阅读器，与组蛋白的乙酰化区域结合并同步基因转录。BET蛋白对正常细胞过程至关重要，因为它们控制细胞周期进程、神经发生、分化以及红细胞生成和精子发生等的成熟过程等。基于研究的证据表明，BET蛋白（主要是BRD4）与多种病理疾病相关，包括癌症、炎症、感染、肾脏疾病和心脏疾病等。为对抗与BET蛋白相关的病理状况，已经开发出一些BET抑制剂，还有一些正在研发中。BET蛋白是当前研究最多的课题之一。本综述提供了关于BET蛋白的基本结构、生物化学、生理作用以及已证实BET蛋白发挥作用的病理状况的简短但全面的知识。本综述还强调了应对与BET蛋白相关病理的当前和未来方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/9aa286efe5cd/fphar-13-818891-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/86608e969ec7/fphar-13-818891-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/9f8a69a66e22/fphar-13-818891-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/69fb9b13a01b/fphar-13-818891-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/9aa286efe5cd/fphar-13-818891-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/86608e969ec7/fphar-13-818891-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/9f8a69a66e22/fphar-13-818891-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/69fb9b13a01b/fphar-13-818891-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/8990909/9aa286efe5cd/fphar-13-818891-g004.jpg

相似文献

1
A Comprehensive Review of BET Protein Biochemistry, Physiology, and Pathological Roles.BET蛋白的生物化学、生理学及病理作用综述
Front Pharmacol. 2022 Mar 25;13:818891. doi: 10.3389/fphar.2022.818891. eCollection 2022.
2
Epigenetic Readers of Lysine Acetylation Regulate Cocaine-Induced Plasticity.赖氨酸乙酰化的表观遗传阅读器调控可卡因诱导的可塑性。
J Neurosci. 2015 Nov 11;35(45):15062-72. doi: 10.1523/JNEUROSCI.0826-15.2015.
3
Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases.含溴结构域和额外末端结构域蛋白作为肾脏疾病新的表观遗传靶点
Front Pharmacol. 2019 Nov 8;10:1315. doi: 10.3389/fphar.2019.01315. eCollection 2019.
4
BET Epigenetic Reader Proteins in Cardiovascular Transcriptional Programs.BET 表观遗传读蛋白在心血管转录程序中的作用。
Circ Res. 2020 Apr 24;126(9):1190-1208. doi: 10.1161/CIRCRESAHA.120.315929. Epub 2020 Apr 23.
5
The Bromodomain and Extra-Terminal Domain (BET) Family: Functional Anatomy of BET Paralogous Proteins.溴结构域与额外末端结构域（BET）家族：BET 旁系同源蛋白的功能剖析
Int J Mol Sci. 2016 Nov 7;17(11):1849. doi: 10.3390/ijms17111849.
6
Bromodomain and extraterminal domain-containing protein inhibition attenuates acute inflammation after spinal cord injury.溴结构域和末端外结构域蛋白抑制物减轻脊髓损伤后的急性炎症。
Exp Neurol. 2018 Nov;309:181-192. doi: 10.1016/j.expneurol.2018.08.005. Epub 2018 Aug 19.
7
BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.BET 溴结构域抑制剂：新颖的设计策略和治疗应用。
Molecules. 2023 Mar 29;28(7):3043. doi: 10.3390/molecules28073043.
8
BRD4 bimodal binding at promoters and drug-induced displacement at Pol II pause sites associates with I-BET sensitivity.BRD4 双模态结合在启动子上，以及药物诱导的在 Pol II 暂停位点的置换与 I-BET 敏感性相关。
Epigenetics Chromatin. 2019 Jul 2;12(1):39. doi: 10.1186/s13072-019-0286-5.
9
Small-Molecule Targeting of BET Proteins in Cancer.小分子靶向 BET 蛋白治疗癌症。
Adv Cancer Res. 2016;131:21-58. doi: 10.1016/bs.acr.2016.04.001. Epub 2016 May 31.
10
BRD3 and BRD4 BET Bromodomain Proteins Differentially Regulate Skeletal Myogenesis.BRD3 和 BRD4 BET 溴结构域蛋白对骨骼成肌分化的调控存在差异。
Sci Rep. 2017 Jul 21;7(1):6153. doi: 10.1038/s41598-017-06483-7.

引用本文的文献

1
BRD4 binds the nucleosome via both histone and DNA interactions.BRD4通过与组蛋白和DNA的相互作用结合核小体。
bioRxiv. 2025 May 30:2025.05.29.656846. doi: 10.1101/2025.05.29.656846.
2
A Minireview on BET Inhibitors: Beyond Bromodomain Targeting.BET抑制剂综述：超越溴结构域靶向作用
Biomedicines. 2025 Mar 1;13(3):594. doi: 10.3390/biomedicines13030594.
3
Therapeutic Targeting of BET Proteins in Sarcoma.肉瘤中BET蛋白的治疗靶点

本文引用的文献

1
Progress in the development of domain selective inhibitors of the bromo and extra terminal domain family (BET) proteins.溴结构域和末端外结构域家族（BET）蛋白的结构选择性抑制剂的研究进展。
Eur J Med Chem. 2021 Dec 15;226:113853. doi: 10.1016/j.ejmech.2021.113853. Epub 2021 Sep 13.
2
Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes.发现选择性 HDAC/BRD4 双重抑制剂作为表观遗传探针。
Eur J Med Chem. 2021 Jan 1;209:112868. doi: 10.1016/j.ejmech.2020.112868. Epub 2020 Oct 13.
3
Bromodomains and Extra-Terminal (BET) Inhibitor JQ1 Suppresses Proliferation of Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolysis.
Mol Cancer Ther. 2025 Sep 2;24(9):1320-1330. doi: 10.1158/1535-7163.MCT-24-1027.
4
A "Goldilocks Zone" for Recruiting BET Proteins with Bromodomain-1-Selective Ligands.招募具有溴结构域 1 选择性配体的 BET 蛋白的“金发姑娘区域”。
ACS Chem Biol. 2024 Nov 15;19(11):2268-2276. doi: 10.1021/acschembio.4c00505. Epub 2024 Oct 14.
5
Precision Targeting of BET Proteins - Navigating Disease Pathways, Inhibitor Insights, and Shaping Therapeutic Frontiers: A Comprehensive Review.BET蛋白的精准靶向——探索疾病途径、抑制剂见解与塑造治疗前沿：全面综述
Curr Drug Targets. 2025;26(3):147-166. doi: 10.2174/0113894501304747240823111337.
6
Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.糖尿病心血管并发症的表观遗传机制：未来治疗的方向。
Mol Med. 2024 Sep 27;30(1):161. doi: 10.1186/s10020-024-00939-z.
7
SARS-CoV-2 E protein interacts with BRD2 and BRD4 SEED domains and alters transcription in a different way than BET inhibition.SARS-CoV-2 E 蛋白与 BRD2 和 BRD4 SEED 结构域相互作用，并以不同于 BET 抑制的方式改变转录。
Cell Mol Life Sci. 2024 Jul 27;81(1):313. doi: 10.1007/s00018-024-05343-8.
8
BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436.BET 靶向 PROTACs 在三阴性乳腺癌细胞系 MDA-MB-231 和 MDA-MB-436 中的作用。
Breast Cancer Res Treat. 2024 Nov;208(1):89-101. doi: 10.1007/s10549-024-07403-w. Epub 2024 Jun 19.
9
Peptide Inhibitor Targeting the Extraterminal Domain in BRD4 Potently Suppresses Breast Cancer Both and .靶向BRD4末端外结构域的肽抑制剂可有效抑制乳腺癌的生长和转移。
J Med Chem. 2024 Apr 25;67(8):6658-6672. doi: 10.1021/acs.jmedchem.4c00141. Epub 2024 Apr 3.
10
Bromodomain Protein-directed Agents and MYC in Small Cell Lung Cancer.溴结构域蛋白靶向药物与小细胞肺癌中的 MYC
Curr Cancer Drug Targets. 2024;24(9):930-940. doi: 10.2174/0115680096272757231211113206.
溴结构域和末端（BET）抑制剂 JQ1 通过抑制 c-Myc 介导的糖酵解来抑制急性淋巴细胞白血病的增殖。
Med Sci Monit. 2020 Apr 8;26:e923411. doi: 10.12659/MSM.923411.
4
Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial.阿巴他用于标准治疗的添加对近期急性冠状动脉综合征和 2 型糖尿病患者主要不良心血管事件的影响：一项随机临床试验。
JAMA. 2020 Apr 28;323(16):1565-1573. doi: 10.1001/jama.2020.3308.
5
Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation.选择性靶向 BET 蛋白的 BD1 和 BD2 在癌症和免疫炎症中的作用。
Science. 2020 Apr 24;368(6489):387-394. doi: 10.1126/science.aaz8455. Epub 2020 Mar 19.
6
P-TEFb as A Promising Therapeutic Target.P-TEFb 作为一种有前途的治疗靶点。
Molecules. 2020 Feb 14;25(4):838. doi: 10.3390/molecules25040838.
7
Jumonji domain-containing protein 6 protein and its role in cancer.Jumonji 结构域包含蛋白 6 及其在癌症中的作用。
Cell Prolif. 2020 Feb;53(2):e12747. doi: 10.1111/cpr.12747. Epub 2020 Jan 21.
8
BRD4 blockage alleviates pathological cardiac hypertrophy through the suppression of fibrosis and inflammation via reducing ROS generation.BRD4 阻断通过减少 ROS 生成来抑制纤维化和炎症，从而减轻病理性心肌肥厚。
Biomed Pharmacother. 2020 Jan;121:109368. doi: 10.1016/j.biopha.2019.109368. Epub 2019 Nov 25.
9
Pharmacological Targeting of BET Bromodomain Proteins in Acute Myeloid Leukemia and Malignant Lymphomas: From Molecular Characterization to Clinical Applications.急性髓系白血病和恶性淋巴瘤中BET溴结构域蛋白的药理学靶向：从分子特征到临床应用
Cancers (Basel). 2019 Oct 2;11(10):1483. doi: 10.3390/cancers11101483.
10
Discovery, structural insight, and bioactivities of BY27 as a selective inhibitor of the second bromodomains of BET proteins.发现、结构见解和 BY27 的生物活性，作为 BET 蛋白第二个溴结构域的选择性抑制剂。
Eur J Med Chem. 2019 Nov 15;182:111633. doi: 10.1016/j.ejmech.2019.111633. Epub 2019 Aug 21.