• 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

PLK1抑制作用会延迟有丝分裂的进入，揭示出哺乳动物细胞在分裂早期磷酸化蛋白质组的变化。

PLK1 inhibition delays mitotic entry revealing changes to the phosphoproteome of mammalian cells early in division.

作者信息

Gobran Monica, Politi Antonio Z, Welp Luisa, Jakobi Jasmin, Urlaub Henning, Lenart Peter

机构信息

Research Group Cytoskeletal Dynamics in Oocytes, Max Planck Institute for Multidisciplinary Sciences, 11 Am Fassberg, 37077, Göttingen, Germany.

Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, 11 Am Fassberg, 37077, Göttingen, Germany.

出版信息

EMBO J. 2025 Apr;44(7):1891-1920. doi: 10.1038/s44318-025-00400-9. Epub 2025 Mar 3.

DOI:10.1038/s44318-025-00400-9
PMID:40033019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11962124/
Abstract

Polo-like kinase 1 (PLK1) is a conserved regulator of cell division. During mitotic prophase, PLK1 contributes to the activation of the cyclin-dependent kinase 1 (CDK1). However, the exact functions of PLK1 in prophase remain incompletely understood. Here, we show that PLK1 inhibition in synchronous G2 cell populations of multiple mammalian cell lines delays or prevents mitotic entry with high variability between individual cells. Using a mathematical model, we recapitulate this phenomenon and provide an explanation for the observed phenotypic variability. We show that PLK1-inhibited cells are delayed in a prophase-like state with low CDK1 activity that increases slowly and gradually over hours. These cells display progressively condensing chromosomes, increased microtubule dynamics, and reorganization of the actin cortex, while the nuclear envelope remains intact. We characterize this state further by phosphoproteomics, revealing phosphorylation of regulators of chromatin organization and the cytoskeleton consistent with the cellular phenotypes. Together, our results indicate that PLK1 inhibition stabilizes cells in a prophase-like state with low CDK1 activity displaying a specific set of early mitotic phosphorylation events.

摘要

Polo样激酶1（PLK1）是细胞分裂的保守调节因子。在有丝分裂前期，PLK1有助于细胞周期蛋白依赖性激酶1（CDK1）的激活。然而，PLK1在前期的确切功能仍未完全了解。在此，我们表明，在多种哺乳动物细胞系的同步G2细胞群体中抑制PLK1会延迟或阻止有丝分裂进入，且单个细胞之间存在高度变异性。使用数学模型，我们重现了这一现象，并对观察到的表型变异性提供了解释。我们表明，PLK1抑制的细胞在类似前期的状态下延迟，CDK1活性低，且在数小时内缓慢逐渐增加。这些细胞显示出染色体逐渐浓缩、微管动力学增加以及肌动蛋白皮层重组，而核膜保持完整。我们通过磷酸化蛋白质组学进一步表征这种状态，揭示染色质组织和细胞骨架调节因子的磷酸化与细胞表型一致。总之，我们的结果表明，PLK1抑制使细胞稳定在类似前期的状态，CDK1活性低，表现出一组特定的早期有丝分裂磷酸化事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/b2824b8e1ec0/44318_2025_400_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/c6cf887b279f/44318_2025_400_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/d874a2c322ad/44318_2025_400_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/208a50bec0a5/44318_2025_400_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/d079dbd853d5/44318_2025_400_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/939d80400328/44318_2025_400_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/0e0eccc5a39f/44318_2025_400_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/1cb00bb6b3cb/44318_2025_400_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/6a7b665f5513/44318_2025_400_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/9f6f1f446ff5/44318_2025_400_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/99689891bedc/44318_2025_400_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/b2824b8e1ec0/44318_2025_400_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/c6cf887b279f/44318_2025_400_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/d874a2c322ad/44318_2025_400_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/208a50bec0a5/44318_2025_400_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/d079dbd853d5/44318_2025_400_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/939d80400328/44318_2025_400_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/0e0eccc5a39f/44318_2025_400_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/1cb00bb6b3cb/44318_2025_400_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/6a7b665f5513/44318_2025_400_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/9f6f1f446ff5/44318_2025_400_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/99689891bedc/44318_2025_400_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2ac/11962124/b2824b8e1ec0/44318_2025_400_Fig11_ESM.jpg

相似文献

1
PLK1 inhibition delays mitotic entry revealing changes to the phosphoproteome of mammalian cells early in division.PLK1抑制作用会延迟有丝分裂的进入，揭示出哺乳动物细胞在分裂早期磷酸化蛋白质组的变化。
EMBO J. 2025 Apr;44(7):1891-1920. doi: 10.1038/s44318-025-00400-9. Epub 2025 Mar 3.
2
FRET-Based Sorting of Live Cells Reveals Shifted Balance between PLK1 and CDK1 Activities During Checkpoint Recovery.基于 FRET 的活细胞分选揭示了在检查点恢复过程中 PLK1 和 CDK1 活性之间的平衡转移。
Cells. 2020 Sep 19;9(9):2126. doi: 10.3390/cells9092126.
3
WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry.WAC 促进 Polo 样激酶 1 的激活以实现及时的有丝分裂进入。
Cell Rep. 2018 Jul 17;24(3):546-556. doi: 10.1016/j.celrep.2018.06.087.
4
Sequential Cdk1 and Plk1 phosphorylation of protein tyrosine phosphatase 1B promotes mitotic cell death.蛋白酪氨酸磷酸酶 1B 的 Cdk1 和 Plk1 顺序磷酸化促进有丝分裂细胞死亡。
Cell Death Dis. 2013 Jan 24;4(1):e468. doi: 10.1038/cddis.2012.208.
5
Cell division cycle 6, a mitotic substrate of polo-like kinase 1, regulates chromosomal segregation mediated by cyclin-dependent kinase 1 and separase.细胞分裂周期蛋白 6，作为 polo 样激酶 1 的有丝分裂底物，调节细胞周期蛋白依赖性激酶 1 和 separase 介导的染色体分离。
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19742-7. doi: 10.1073/pnas.1013557107. Epub 2010 Nov 1.
6
Polo-like kinase 1 inhibits DNA damage response during mitosis.Polo样激酶1在有丝分裂过程中抑制DNA损伤反应。
Cell Cycle. 2015;14(2):219-31. doi: 10.4161/15384101.2014.977067.
7
Polo-like kinase 1 phosphorylation of p150Glued facilitates nuclear envelope breakdown during prophase.丝氨酸/苏氨酸激酶 Polo 样激酶 1 对 p150Glued 的磷酸化作用有助于核膜解体在前期进行。
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14633-8. doi: 10.1073/pnas.1006615107. Epub 2010 Aug 2.
8
Mitotic entry: The interplay between Cdk1, Plk1 and Bora.有丝分裂进入：细胞周期蛋白依赖性激酶1（Cdk1）、极光激酶（Plk1）与博拉蛋白（Bora）之间的相互作用
Cell Cycle. 2016 Dec;15(23):3177-3182. doi: 10.1080/15384101.2016.1249544. Epub 2016 Nov 10.
9
PLK1 Activation in Late G2 Sets Up Commitment to Mitosis.G2晚期的PLK1激活促使细胞进入有丝分裂。
Cell Rep. 2017 Jun 6;19(10):2060-2073. doi: 10.1016/j.celrep.2017.05.031.
10
BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis.在有丝分裂中，由 CDK1 引发的 BUB1 和 CENP-U 是 PLK1 动粒的主要受体。
Mol Cell. 2021 Jan 7;81(1):67-87.e9. doi: 10.1016/j.molcel.2020.10.040. Epub 2020 Nov 27.

本文引用的文献

1
The PRIDE database at 20 years: 2025 update.20年的PRIDE数据库：2025年更新
Nucleic Acids Res. 2025 Jan 6;53(D1):D543-D553. doi: 10.1093/nar/gkae1011.
2
Live-cell imaging defines a threshold in CDK activity at the G2/M transition.活细胞成像在 G2/M 转换时定义了 CDK 活性的阈值。
Dev Cell. 2024 Feb 26;59(4):545-557.e4. doi: 10.1016/j.devcel.2023.12.014. Epub 2024 Jan 15.
3
Mechanisms of nuclear pore complex disassembly by the mitotic Polo-like kinase 1 (PLK-1) in embryos.有丝分裂时期 Polo 样激酶 1（PLK-1）在 胚胎中对核孔复合体的解体机制。
Sci Adv. 2023 Jul 21;9(29):eadf7826. doi: 10.1126/sciadv.adf7826. Epub 2023 Jul 19.
4
Microtubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG.在间期细胞中，微管核形成和 γTuRC 中心体定位需要 ch-TOG。
Nat Commun. 2023 Jan 26;14(1):289. doi: 10.1038/s41467-023-35955-w.
5
The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest.2023 年的 STRING 数据库：针对任何感兴趣的测序基因组的蛋白质-蛋白质关联网络和功能富集分析。
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646. doi: 10.1093/nar/gkac1000.
6
TrackMate 7: integrating state-of-the-art segmentation algorithms into tracking pipelines.TrackMate 7：将最先进的分割算法集成到跟踪管道中。
Nat Methods. 2022 Jul;19(7):829-832. doi: 10.1038/s41592-022-01507-1. Epub 2022 Jun 2.
7
CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry.CDK1-cyclin-B1 诱导黏着斑激酶降解驱动有丝分裂起始时黏着斑解聚。
Nat Cell Biol. 2022 May;24(5):723-736. doi: 10.1038/s41556-022-00886-z. Epub 2022 Apr 25.
8
Mapping the invisible chromatin transactions of prophase chromosome remodeling.绘制前期染色体重塑中不可见的染色质转位。
Mol Cell. 2022 Feb 3;82(3):696-708.e4. doi: 10.1016/j.molcel.2021.12.039. Epub 2022 Jan 31.
9
Low Cell Number Proteomic Analysis Using In-Cell Protease Digests Reveals a Robust Signature for Cell Cycle State Classification.低细胞数蛋白质组学分析采用细胞内蛋白酶消化可揭示细胞周期状态分类的稳健特征。
Mol Cell Proteomics. 2022 Jan;21(1):100169. doi: 10.1016/j.mcpro.2021.100169. Epub 2021 Nov 4.
10
Enhancing the biocompatibility of rhodamine fluorescent probes by a neighbouring group effect.通过邻基效应增强罗丹明荧光探针的生物相容性。
Chem Sci. 2020 Jun 22;11(28):7313-7323. doi: 10.1039/d0sc02154g. eCollection 2020 Jul 28.