• 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

长城磷酸化内硫素既是PP2A-B55异源三聚体的抑制剂又是其底物。

Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers.

作者信息

Williams Byron C, Filter Joshua J, Blake-Hodek Kristina A, Wadzinski Brian E, Fuda Nicholas J, Shalloway David, Goldberg Michael L

机构信息

Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.

出版信息

Elife. 2014 Mar 11;3:e01695. doi: 10.7554/eLife.01695.

DOI:10.7554/eLife.01695
PMID:24618897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3949306/
Abstract

During M phase, Endosulfine (Endos) family proteins are phosphorylated by Greatwall kinase (Gwl), and the resultant pEndos inhibits the phosphatase PP2A-B55, which would otherwise prematurely reverse many CDK-driven phosphorylations. We show here that PP2A-B55 is the enzyme responsible for dephosphorylating pEndos during M phase exit. The kinetic parameters for PP2A-B55's action on pEndos are orders of magnitude lower than those for CDK-phosphorylated substrates, suggesting a simple model for PP2A-B55 regulation that we call inhibition by unfair competition. As the name suggests, during M phase PP2A-B55's attention is diverted to pEndos, which binds much more avidly and is dephosphorylated more slowly than other substrates. When Gwl is inactivated during the M phase-to-interphase transition, the dynamic balance changes: pEndos dephosphorylated by PP2A-B55 cannot be replaced, so the phosphatase can refocus its attention on CDK-phosphorylated substrates. This mechanism explains simultaneously how PP2A-B55 and Gwl together regulate pEndos, and how pEndos controls PP2A-B55. DOI: http://dx.doi.org/10.7554/eLife.01695.001.

摘要

在M期，硫丹（Endos）家族蛋白被长城激酶（Gwl）磷酸化，产生的磷酸化硫丹（pEndos）抑制磷酸酶PP2A - B55，否则该磷酸酶会过早逆转许多细胞周期蛋白依赖性激酶（CDK）驱动的磷酸化反应。我们在此表明，PP2A - B55是在M期退出过程中负责使pEndos去磷酸化的酶。PP2A - B55作用于pEndos的动力学参数比其作用于CDK磷酸化底物的动力学参数低几个数量级，这提示了一种我们称为不公平竞争抑制的PP2A - B55调节简单模型。顾名思义，在M期，PP2A - B55的注意力被转移到pEndos上，pEndos比其他底物结合得更紧密且去磷酸化更慢。当Gwl在M期向间期转变过程中失活时，动态平衡发生变化：被PP2A - B55去磷酸化的pEndos无法被替代，因此该磷酸酶能够将注意力重新集中到CDK磷酸化的底物上。这一机制同时解释了PP2A - B55和Gwl如何共同调节pEndos，以及pEndos如何控制PP2A - B55。DOI: http://dx.doi.org/10.7554/eLife.01695.001 。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/4ee5a56657f1/elife01695f011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/4086cc28882e/elife01695f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/434ea7a6a4ab/elife01695f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/c209d0880e94/elife01695fs001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/8f6334bcae0a/elife01695fs002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/5c43fa8d1391/elife01695fs003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/7603b6b2dc9c/elife01695fs004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/2743d38116e4/elife01695fs005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/331fadbdbbda/elife01695fs006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/b3ecb6678163/elife01695f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/612d28719c30/elife01695fs007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/0b8a9bf48cbc/elife01695f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/b23d9f38fb5f/elife01695f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/f449dbe4513d/elife01695f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/1ba03347d23a/elife01695fs008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/e6ac67a7cc2a/elife01695fs009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/818c515a0adc/elife01695f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/15cc79679cac/elife01695f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/3a89c0142f3a/elife01695f009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/a114795e0e76/elife01695f010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/5fe2e1f52ee6/elife01695fs010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/4ee5a56657f1/elife01695f011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/4086cc28882e/elife01695f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/434ea7a6a4ab/elife01695f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/c209d0880e94/elife01695fs001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/8f6334bcae0a/elife01695fs002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/5c43fa8d1391/elife01695fs003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/7603b6b2dc9c/elife01695fs004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/2743d38116e4/elife01695fs005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/331fadbdbbda/elife01695fs006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/b3ecb6678163/elife01695f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/612d28719c30/elife01695fs007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/0b8a9bf48cbc/elife01695f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/b23d9f38fb5f/elife01695f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/f449dbe4513d/elife01695f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/1ba03347d23a/elife01695fs008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/e6ac67a7cc2a/elife01695fs009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/818c515a0adc/elife01695f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/15cc79679cac/elife01695f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/3a89c0142f3a/elife01695f009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/a114795e0e76/elife01695f010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/5fe2e1f52ee6/elife01695fs010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc1/3949306/4ee5a56657f1/elife01695f011.jpg

相似文献

1
Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers.长城磷酸化内硫素既是PP2A-B55异源三聚体的抑制剂又是其底物。
Elife. 2014 Mar 11;3:e01695. doi: 10.7554/eLife.01695.
2
Bypassing the Greatwall-Endosulfine pathway: plasticity of a pivotal cell-cycle regulatory module in Drosophila melanogaster and Caenorhabditis elegans.绕过长城-Endosulfine 途径：果蝇和秀丽隐杆线虫关键细胞周期调控模块的可塑性。
Genetics. 2012 Aug;191(4):1181-97. doi: 10.1534/genetics.112.140574. Epub 2012 May 29.
3
Greatwall-Endosulfine: A Molecular Switch that Regulates PP2A/B55 Protein Phosphatase Activity in Dividing and Quiescent Cells.长城内硫酯酶：调控有丝分裂和静止细胞中 PP2A/B55 蛋白磷酸酶活性的分子开关。
Int J Mol Sci. 2019 Dec 10;20(24):6228. doi: 10.3390/ijms20246228.
4
Spatial regulation of greatwall by Cdk1 and PP2A-Tws in the cell cycle.细胞周期中Cdk1和PP2A-Tws对greatwall的空间调控。
Cell Cycle. 2016;15(4):528-39. doi: 10.1080/15384101.2015.1127476.
5
Suppression of scant identifies Endos as a substrate of greatwall kinase and a negative regulator of protein phosphatase 2A in mitosis.抑制 scant 鉴定 Endos 为有丝分裂中 greatwall 激酶的底物和蛋白磷酸酶 2A 的负调节剂。
PLoS Genet. 2011 Aug;7(8):e1002225. doi: 10.1371/journal.pgen.1002225. Epub 2011 Aug 11.
6
Regulation of Greatwall kinase during Xenopus oocyte maturation.沃尔夫冈激酶在爪蟾卵母细胞成熟过程中的调控作用。
Mol Biol Cell. 2011 Jul 1;22(13):2157-64. doi: 10.1091/mbc.E11-01-0008. Epub 2011 May 5.
7
Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression.Fcp1磷酸酶调控Greatwall激酶以促进PP2A-B55激活和有丝分裂进程。
Elife. 2015 Dec 14;4:e10399. doi: 10.7554/eLife.10399.
8
PP2A/B55 and Fcp1 regulate Greatwall and Ensa dephosphorylation during mitotic exit.PP2A/B55 和 Fcp1 调节有丝分裂后期 Greatwall 和 Ensa 的去磷酸化。
PLoS Genet. 2014 Jan;10(1):e1004004. doi: 10.1371/journal.pgen.1004004. Epub 2014 Jan 2.
9
Protein phosphatase 1 is essential for Greatwall inactivation at mitotic exit.蛋白磷酸酶1对于有丝分裂退出时Greatwall的失活至关重要。
EMBO Rep. 2015 Nov;16(11):1501-10. doi: 10.15252/embr.201540876. Epub 2015 Sep 22.
10
Regulation of α-endosulfine, an inhibitor of protein phosphatase 2A, by multisite phosphorylation.α-内磺肽（一种蛋白磷酸酶 2A 的抑制剂）通过多位点磷酸化进行调节。
FEBS J. 2014 Feb;281(4):1159-69. doi: 10.1111/febs.12685. Epub 2014 Jan 9.

引用本文的文献

1
The balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells.B55α与Greatwall表达水平之间的平衡预示着癌细胞对Greatwall抑制的敏感性。
Nat Commun. 2025 Aug 27;16(1):8016. doi: 10.1038/s41467-025-62943-z.
2
Unveiling an Arpp-19 phosphorylation switch that grants chromosome stability.揭示一种赋予染色体稳定性的Arpp-19磷酸化开关。
Commun Biol. 2025 May 30;8(1):841. doi: 10.1038/s42003-025-08281-8.
3
The MAST kinase KIN-4 carries out mitotic entry functions of Greatwall in C. elegans.

本文引用的文献

1
PP2A/B55 and Fcp1 regulate Greatwall and Ensa dephosphorylation during mitotic exit.PP2A/B55 和 Fcp1 调节有丝分裂后期 Greatwall 和 Ensa 的去磷酸化。
PLoS Genet. 2014 Jan;10(1):e1004004. doi: 10.1371/journal.pgen.1004004. Epub 2014 Jan 2.
2
Regulation of α-endosulfine, an inhibitor of protein phosphatase 2A, by multisite phosphorylation.α-内磺肽（一种蛋白磷酸酶 2A 的抑制剂）通过多位点磷酸化进行调节。
FEBS J. 2014 Feb;281(4):1159-69. doi: 10.1111/febs.12685. Epub 2014 Jan 9.
3
The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome separation.
MAST激酶KIN-4在秀丽隐杆线虫中执行Greatwall的有丝分裂进入功能。
EMBO J. 2025 Apr;44(7):1943-1974. doi: 10.1038/s44318-025-00364-w. Epub 2025 Feb 17.
4
PP2A-Tws dephosphorylates Map205, is required for Polo localization to microtubules and promotes cytokinesis in Drosophila.PP2A-Tws使Map205去磷酸化，是Polo定位于微管所必需的，并促进果蝇的胞质分裂。
Cell Div. 2024 Dec 28;19(1):36. doi: 10.1186/s13008-024-00141-x.
5
Inducible degradation-coupled phosphoproteomics identifies PP2A as a novel eisosome regulator.可诱导的降解偶联磷酸化蛋白质组学鉴定出PP2A为一种新型的内质体调节器。
Front Cell Dev Biol. 2024 Aug 21;12:1451027. doi: 10.3389/fcell.2024.1451027. eCollection 2024.
6
Deficiency of , a mitotic regulator, results in cell detachment from developing tissues of zebrafish embryos.一种有丝分裂调节因子的缺乏会导致斑马鱼胚胎发育组织中的细胞脱离。
Front Cell Dev Biol. 2024 Mar 11;12:1375655. doi: 10.3389/fcell.2024.1375655. eCollection 2024.
7
Increases in cyclin A/Cdk activity and in PP2A-B55 inhibition by FAM122A are key mitosis-inducing events.FAM122A 引起的细胞周期蛋白 A/CDK 活性的增加和 PP2A-B55 的抑制是关键的有丝分裂诱导事件。
EMBO J. 2024 Mar;43(6):993-1014. doi: 10.1038/s44318-024-00054-z. Epub 2024 Feb 20.
8
Reusable rule-based cell cycle model explains compartment-resolved dynamics of 16 observables in RPE-1 cells.基于规则的可重复细胞周期模型解释了 RPE-1 细胞中 16 个可观察变量的隔室分辨动力学。
PLoS Comput Biol. 2024 Jan 8;20(1):e1011151. doi: 10.1371/journal.pcbi.1011151. eCollection 2024 Jan.
9
Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19.PP2A：B55-FAM122A 和 PP2A：B55-ARPP19 的冷冻电镜结构。
Nature. 2024 Jan;625(7993):195-203. doi: 10.1038/s41586-023-06870-3. Epub 2023 Dec 20.
10
Phosphatase specificity principles uncovered by MRBLE:Dephos and global substrate identification.MRBLE 揭示的磷酸酶特异性原则：Dephos 和全局底物鉴定。
Mol Syst Biol. 2023 Dec 6;19(12):e11782. doi: 10.15252/msb.202311782. Epub 2023 Nov 2.
BEG（PP2A-B55/ENSA/Greatwall）通路确保胞质分裂紧随染色体分离之后。
Mol Cell. 2013 Nov 7;52(3):393-405. doi: 10.1016/j.molcel.2013.09.005. Epub 2013 Oct 10.
4
On the regulation of protein phosphatase 2A and its role in controlling entry into and exit from mitosis.关于蛋白磷酸酶2A的调控及其在控制有丝分裂进出过程中的作用。
Adv Biol Regul. 2013 May;53(2):173-8. doi: 10.1016/j.jbior.2013.04.001. Epub 2013 Apr 29.
5
Deciphering the New Role of the Greatwall/PP2A Pathway in Cell Cycle Control.解读长城/蛋白磷酸酶2A通路在细胞周期调控中的新作用
Genes Cancer. 2012 Nov;3(11-12):712-20. doi: 10.1177/1947601912473478.
6
BRENDA in 2013: integrated reactions, kinetic data, enzyme function data, improved disease classification: new options and contents in BRENDA.BRENDA 数据库在 2013 年：整合了反应、动力学数据、酶功能数据，改进了疾病分类：BRENDA 数据库新增选项和内容。
Nucleic Acids Res. 2013 Jan;41(Database issue):D764-72. doi: 10.1093/nar/gks1049. Epub 2012 Nov 29.
7
The RNA polymerase II CTD coordinates transcription and RNA processing.RNA 聚合酶 II CTD 协调转录和 RNA 加工。
Genes Dev. 2012 Oct 1;26(19):2119-37. doi: 10.1101/gad.200303.112.
8
Greatwall kinase and cyclin B-Cdk1 are both critical constituents of M-phase-promoting factor.长城激酶和细胞周期蛋白 B-Cdk1 都是促进有丝分裂因子的关键组成部分。
Nat Commun. 2012;3:1059. doi: 10.1038/ncomms2062.
9
The overlooked greatwall: a new perspective on mitotic control.被忽视的“长城”：有丝分裂调控的新视角。
Open Biol. 2012 Mar;2(3):120023. doi: 10.1098/rsob.120023.
10
Fcp1 dephosphorylation of the RNA polymerase II C-terminal domain is required for efficient transcription of heat shock genes.Fcp1 去磷酸化 RNA 聚合酶 II C 端结构域对于热休克基因的高效转录是必需的。
Mol Cell Biol. 2012 Sep;32(17):3428-37. doi: 10.1128/MCB.00247-12. Epub 2012 Jun 25.