• 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

双氧化酶产生的活性氧激活 ATR/Chk1 诱导气管细胞 G2 期阻滞。

Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in tracheoblasts.

机构信息

Regulation of Cell Fate, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, India.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.

出版信息

Elife. 2021 Oct 8;10:e68636. doi: 10.7554/eLife.68636.

DOI:10.7554/eLife.68636
PMID:34622778
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8594940/
Abstract

Progenitors of the thoracic tracheal system of adult (tracheoblasts) arrest in G2 during larval life and rekindle a mitotic program subsequently. G2 arrest is dependent on ataxia telangiectasia mutated and rad3-related kinase (ATR)-dependent phosphorylation of checkpoint kinase 1 (Chk1) that is actuated in the absence of detectable DNA damage. We are interested in the mechanisms that activate ATR/Chk1 (Kizhedathu et al., 2018; Kizhedathu et al., 2020). Here we report that levels of reactive oxygen species (ROS) are high in arrested tracheoblasts and decrease upon mitotic re-entry. High ROS is dependent on expression of Duox, an HO generating dual oxidase. ROS quenching by overexpression of superoxide dismutase 1, or by knockdown of Duox, abolishes Chk1 phosphorylation and results in precocious proliferation. Tracheae deficient in Duox, or deficient in both Duox and regulators of DNA damage-dependent ATR/Chk1 activation (ATRIP/TOPBP1/claspin), can induce phosphorylation of Chk1 in response to micromolar concentrations of HO in minutes. The findings presented reveal that HO activates ATR/Chk1 in tracheoblasts by a non-canonical, potentially direct, mechanism.

摘要

成体胸气管系统的祖细胞（tracheoblasts）在幼虫期的 G2 期停滞，并随后重新启动有丝分裂程序。G2 期停滞依赖于共济失调毛细血管扩张突变和 rad3 相关激酶（ATR）依赖性磷酸化检查点激酶 1（Chk1），而在没有检测到 DNA 损伤的情况下，ATR/Chk1（Kizhedathu 等人，2018 年；Kizhedathu 等人，2020 年）。我们对激活 ATR/Chk1 的机制感兴趣。在这里，我们报告说，停滞的气管细胞中的活性氧（ROS）水平很高，并且在有丝分裂重新进入时会降低。高 ROS 依赖于 HO 生成的双氧化酶 Duox 的表达。通过过表达超氧化物歧化酶 1 或敲低 Duox 来清除 ROS，会消除 Chk1 的磷酸化，并导致早熟增殖。缺乏 Duox 的气管或缺乏 Duox 和 DNA 损伤依赖性 ATR/Chk1 激活调节剂（ATRIP/TOPBP1/claspin）的气管，在几分钟内可以对毫摩尔浓度的 HO 做出 Chk1 磷酸化的反应。这些发现表明，HO 通过一种非典型的、潜在的直接机制，在气管细胞中激活 ATR/Chk1。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/28a0ac7cc0f0/elife-68636-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/1452b9d734b4/elife-68636-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/36e8ced4d4f9/elife-68636-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/8ed746a54743/elife-68636-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/8f38b2f0f348/elife-68636-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/c33414508548/elife-68636-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/af8730e2cc08/elife-68636-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/d7a58608d2e6/elife-68636-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/ddb76c417f45/elife-68636-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/57a8ce2923df/elife-68636-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/28a0ac7cc0f0/elife-68636-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/1452b9d734b4/elife-68636-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/36e8ced4d4f9/elife-68636-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/8ed746a54743/elife-68636-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/8f38b2f0f348/elife-68636-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/c33414508548/elife-68636-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/af8730e2cc08/elife-68636-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/d7a58608d2e6/elife-68636-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/ddb76c417f45/elife-68636-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/57a8ce2923df/elife-68636-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ef5/8594940/28a0ac7cc0f0/elife-68636-fig5-figsupp1.jpg

相似文献

1
Duox-generated reactive oxygen species activate ATR/Chk1 to induce G2 arrest in tracheoblasts.双氧化酶产生的活性氧激活 ATR/Chk1 诱导气管细胞 G2 期阻滞。
Elife. 2021 Oct 8;10:e68636. doi: 10.7554/eLife.68636.
2
Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila.ATR (mei-41)/Chk1(Grapes) 通过负调控 G2-M 促进果蝇气管成纤维细胞的生长和气管的肥大。
Elife. 2018 Apr 16;7:e29988. doi: 10.7554/eLife.29988.
3
Multiple Wnts act synergistically to induce Chk1/Grapes expression and mediate G2 arrest in tracheoblasts.多种 Wnt 蛋白协同作用诱导 Chk1/Grapes 表达并介导气管细胞的 G2 期阻滞。
Elife. 2020 Sep 2;9:e57056. doi: 10.7554/eLife.57056.
4
Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks.果蝇 Claspin 对于由 DNA 复制压力诱导而非 DNA 双链断裂诱导的 G2 期阻滞是必需的。
DNA Repair (Amst). 2012 Sep 1;11(9):741-52. doi: 10.1016/j.dnarep.2012.06.007. Epub 2012 Jul 15.
5
UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway.紫外线诱导的 G2 检验点依赖于 p38MAPK 和 ATR-Chk1 通路的最小激活。
J Cell Sci. 2013 May 1;126(Pt 9):1923-30. doi: 10.1242/jcs.118265. Epub 2013 Feb 27.
6
Bortezomib induces G2-M arrest in human colon cancer cells through ROS-inducible phosphorylation of ATM-CHK1.硼替佐米通过 ROS 诱导的 ATM-CHK1 磷酸化诱导人结肠癌细胞 G2-M 期阻滞。
Int J Oncol. 2012 Jul;41(1):76-82. doi: 10.3892/ijo.2012.1448. Epub 2012 Apr 26.
7
Tethering DNA damage checkpoint mediator proteins topoisomerase IIbeta-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1).将 DNA 损伤检查点介质蛋白拓扑异构酶 IIβ结合蛋白 1（TopBP1）和 Claspin 连接到 DNA 上，可激活共济失调毛细血管扩张突变和 RAD3 相关（ATR）对检查点激酶 1（Chk1）的磷酸化。
J Biol Chem. 2011 Jun 3;286(22):19229-36. doi: 10.1074/jbc.M111.237958. Epub 2011 Apr 18.
8
Regulation of ATR-CHK1 signaling by ubiquitination of CLASPIN.CLASPIN 的泛素化调节 ATR-CHK1 信号通路。
Biochem Soc Trans. 2022 Oct 31;50(5):1471-1480. doi: 10.1042/BST20220729.
9
Reconstitution of human claspin-mediated phosphorylation of Chk1 by the ATR (ataxia telangiectasia-mutated and rad3-related) checkpoint kinase.由 ATR（共济失调毛细血管扩张症突变和 rad3 相关）检查点激酶重建人 claspin 介导的 Chk1 磷酸化。
J Biol Chem. 2009 Nov 27;284(48):33107-14. doi: 10.1074/jbc.M109.064485. Epub 2009 Oct 14.
10
Dissecting cellular responses to irradiation via targeted disruptions of the ATM-CHK1-PP2A circuit.通过靶向破坏 ATM-CHK1-PP2A 通路来解析细胞对辐照的反应。
Cell Cycle. 2013 Apr 1;12(7):1105-18. doi: 10.4161/cc.24127. Epub 2013 Mar 5.

引用本文的文献

1
DNA damage response regulator ATR licenses PINK1-mediated mitophagy.DNA损伤反应调节因子ATR许可PINK1介导的线粒体自噬。
Nucleic Acids Res. 2025 Feb 27;53(5). doi: 10.1093/nar/gkaf178.
2
Ionizing radiation triggers mitophagy to enhance DNA damage in cancer cells.电离辐射引发线粒体自噬以增强癌细胞中的DNA损伤。
Cell Death Discov. 2023 Jul 28;9(1):267. doi: 10.1038/s41420-023-01573-0.
3
Screening of Drosophila microRNA-degradation sequences reveals Argonaute1 mRNA's role in regulating miR-999.果蝇 microRNA 降解序列的筛选揭示了 Argonaute1 mRNA 在调节 miR-999 中的作用。

本文引用的文献

1
Oxidative stress associated metabolic adaptations regulate radioresistance in human lung cancer cells.氧化应激相关代谢适应性调节人肺癌细胞的放射抵抗性。
J Photochem Photobiol B. 2020 Dec;213:112080. doi: 10.1016/j.jphotobiol.2020.112080. Epub 2020 Nov 13.
2
Multiple Wnts act synergistically to induce Chk1/Grapes expression and mediate G2 arrest in tracheoblasts.多种 Wnt 蛋白协同作用诱导 Chk1/Grapes 表达并介导气管细胞的 G2 期阻滞。
Elife. 2020 Sep 2;9:e57056. doi: 10.7554/eLife.57056.
3
ROS and the DNA damage response in cancer.
Nat Commun. 2023 Apr 13;14(1):2108. doi: 10.1038/s41467-023-37819-9.
4
Dual Oxidase, a Hydrogen-Peroxide-Producing Enzyme, Regulates Neuronal Oxidative Damage and Animal Lifespan in .双氧化酶，一种产生过氧化氢的酶，调节 中的神经元氧化损伤和动物寿命。
Cells. 2022 Jun 29;11(13):2059. doi: 10.3390/cells11132059.
活性氧（ROS）与癌症中的 DNA 损伤反应。
Redox Biol. 2019 Jul;25:101084. doi: 10.1016/j.redox.2018.101084. Epub 2018 Dec 21.
4
Overexpression of the ATR homologous checkpoint kinase Mei-41 induces a G2/M checkpoint in imaginal tissue.ATR同源检查点激酶Mei-41的过表达在成虫盘组织中诱导了G2/M检查点。
Hereditas. 2018 Sep 6;155:27. doi: 10.1186/s41065-018-0066-4. eCollection 2018.
5
SWISS-MODEL: homology modelling of protein structures and complexes.SWISS-MODEL：蛋白质结构和复合物的同源建模。
Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303. doi: 10.1093/nar/gky427.
6
Reactive Oxygen Species-Mediated Tumor Microenvironment Transformation: The Mechanism of Radioresistant Gastric Cancer.活性氧介导的肿瘤微环境转化：耐辐射胃癌的机制。
Oxid Med Cell Longev. 2018 Mar 27;2018:5801209. doi: 10.1155/2018/5801209. eCollection 2018.
7
DUOXA1-mediated ROS production promotes cisplatin resistance by activating ATR-Chk1 pathway in ovarian cancer.DUOXA1 介导的活性氧产生通过激活 ATR-Chk1 通路促进卵巢癌对顺铂的耐药性。
Cancer Lett. 2018 Aug 1;428:104-116. doi: 10.1016/j.canlet.2018.04.029. Epub 2018 Apr 26.
8
Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila.ATR (mei-41)/Chk1(Grapes) 通过负调控 G2-M 促进果蝇气管成纤维细胞的生长和气管的肥大。
Elife. 2018 Apr 16;7:e29988. doi: 10.7554/eLife.29988.
9
Cryo-EM structure of human ATR-ATRIP complex.人类 ATR-ATRIP 复合物的冷冻电镜结构。
Cell Res. 2018 Feb;28(2):143-156. doi: 10.1038/cr.2017.158. Epub 2017 Dec 22.
10
ROS and ROS-Mediated Cellular Signaling.活性氧（ROS）与 ROS 介导的细胞信号转导。
Oxid Med Cell Longev. 2016;2016:4350965. doi: 10.1155/2016/4350965. Epub 2016 Feb 22.