• 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

有丝分裂期间MELK的时空调控。

Spatiotemporal regulation of MELK during mitosis.

作者信息

Majumdar Sreemita, Liu Song-Tao

机构信息

Department of Biological Sciences, University of Toledo, Toledo, OH, United States.

出版信息

Front Cell Dev Biol. 2024 Sep 16;12:1406940. doi: 10.3389/fcell.2024.1406940. eCollection 2024.

DOI:10.3389/fcell.2024.1406940
PMID:39355119
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11443572/
Abstract

Maternal Embryonic Leucine Zipper Kinase (MELK) has been studied intensively in recent years due to its overexpression in multiple cancers. However, the cell biology of MELK remains less characterized despite its well-documented association with mitosis. Here we report a distinctive pattern of human MELK that translocates from the cytoplasm to cell cortex within 3 min of anaphase onset. The cortex association lasts about 30 min till telophase. The spatiotemporal specific localization of MELK depends on the interaction between its Threonine-Proline (TP) rich domain and kinase associated 1 (KA1) domain, which is regulated by CDK1 kinase and PP4 protein phosphatase. KA1 domains are known to regulate kinase activities through various intramolecular interactions. Our results revealed a new role for KA1 domain to control subcellular localization of a protein kinase.

摘要

近年来，母源胚胎亮氨酸拉链激酶（MELK）因其在多种癌症中的过表达而受到广泛研究。然而，尽管有充分的文献记载MELK与有丝分裂相关，但其细胞生物学特性仍不太清楚。在此，我们报道了人类MELK的一种独特模式，即在后期开始后3分钟内从细胞质转移到细胞皮层。皮层结合持续约30分钟直至末期。MELK的时空特异性定位取决于其富含苏氨酸-脯氨酸（TP）的结构域与激酶相关1（KA1）结构域之间的相互作用，这一相互作用受CDK1激酶和PP4蛋白磷酸酶的调节。已知KA1结构域通过各种分子内相互作用调节激酶活性。我们的结果揭示了KA1结构域在控制蛋白激酶亚细胞定位方面的新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/371f20bf92f3/fcell-12-1406940-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/1f54a14bbed2/fcell-12-1406940-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/a0046f3be324/fcell-12-1406940-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/e34de25e0517/fcell-12-1406940-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/1d6b5bca096e/fcell-12-1406940-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/371f20bf92f3/fcell-12-1406940-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/1f54a14bbed2/fcell-12-1406940-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/a0046f3be324/fcell-12-1406940-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/e34de25e0517/fcell-12-1406940-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/1d6b5bca096e/fcell-12-1406940-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bc6/11443572/371f20bf92f3/fcell-12-1406940-g005.jpg

相似文献

1
Spatiotemporal regulation of MELK during mitosis.有丝分裂期间MELK的时空调控。
Front Cell Dev Biol. 2024 Sep 16;12:1406940. doi: 10.3389/fcell.2024.1406940. eCollection 2024.
2
Arrestin-3 interaction with maternal embryonic leucine-zipper kinase.抑制素结合蛋白与母源性胚胎亮氨酸拉链激酶相互作用
Cell Signal. 2019 Nov;63:109366. doi: 10.1016/j.cellsig.2019.109366. Epub 2019 Jul 25.
3
Cloning, tissue distribution, expression pattern, and function of porcine maternal embryonic leucine zipper kinase.猪母体胚胎亮氨酸拉链激酶的克隆、组织分布、表达模式及功能
Ann Transl Med. 2020 Mar;8(5):239. doi: 10.21037/atm.2020.03.46.
4
Cortical localization of maternal embryonic leucine zipper kinase (MELK) implicated in cytokinesis in early xenopus embryos.母体胚胎亮氨酸拉链激酶（MELK）在非洲爪蟾早期胚胎胞质分裂中的皮质定位。
Commun Integr Biol. 2011 Jul;4(4):483-5. doi: 10.4161/cib.15669. Epub 2011 Jul 1.
5
Mass spectrometry-based selectivity profiling identifies a highly selective inhibitor of the kinase MELK that delays mitotic entry in cancer cells.基于质谱的选择性分析鉴定出一种高度选择性的激酶 MELK 抑制剂，该抑制剂可延迟癌细胞有丝分裂的进入。
J Biol Chem. 2020 Feb 21;295(8):2359-2374. doi: 10.1074/jbc.RA119.011083. Epub 2020 Jan 2.
6
Maternal embryonic leucine zipper kinase (MELK): a novel regulator in cell cycle control, embryonic development, and cancer.母源胚胎亮氨酸拉链激酶（MELK）：细胞周期调控、胚胎发育和癌症中的新型调节因子。
Int J Mol Sci. 2013 Oct 31;14(11):21551-60. doi: 10.3390/ijms141121551.
7
Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family.母源胚胎亮氨酸拉链激酶（MELK）通过与Bcl-2家族的促凋亡成员Bcl-G相互作用参与乳腺癌发生。
Breast Cancer Res. 2007;9(1):R17. doi: 10.1186/bcr1650.
8
Structural basis for the regulation of maternal embryonic leucine zipper kinase.母源胚胎亮氨酸拉链激酶调控的结构基础。
PLoS One. 2013 Jul 26;8(7):e70031. doi: 10.1371/journal.pone.0070031. Print 2013.
9
Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival.有丝分裂期的MELK-eIF4B信号传导控制蛋白质合成和肿瘤细胞存活。
Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):9810-5. doi: 10.1073/pnas.1606862113. Epub 2016 Aug 15.
10
Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit.母源胚胎亮氨酸拉链激酶在有丝分裂中通过磷酸化稳定，并在有丝分裂退出时部分降解。
Exp Cell Res. 2010 Aug 1;316(13):2166-73. doi: 10.1016/j.yexcr.2010.04.019. Epub 2010 Apr 24.

本文引用的文献

1
UCSF ChimeraX: Tools for structure building and analysis.UCSF ChimeraX：结构构建和分析工具。
Protein Sci. 2023 Nov;32(11):e4792. doi: 10.1002/pro.4792.
2
Structure of the Caenorhabditis elegans m6A methyltransferase METT10 that regulates SAM homeostasis.秀丽隐杆线虫 m6A 甲基转移酶 METT10 的结构，该酶调节 SAM 平衡。
Nucleic Acids Res. 2023 Mar 21;51(5):2434-2446. doi: 10.1093/nar/gkad081.
3
Structure of the Lifeact-F-actin complex.Lifeact-F-actin 复合物的结构。
PLoS Biol. 2020 Nov 20;18(11):e3000925. doi: 10.1371/journal.pbio.3000925. eCollection 2020 Nov.
4
Enigmatic MELK: The controversy surrounding its complex role in cancer.神秘的 MELK：其在癌症中复杂作用引发的争议。
J Biol Chem. 2020 Jun 12;295(24):8195-8203. doi: 10.1074/jbc.REV120.013433. Epub 2020 Apr 29.
5
Mechanistic insights into m6A modification of U6 snRNA by human METTL16.解析 m6A 修饰 U6 snRNA 过程中的人类 METTL16 作用机制。
Nucleic Acids Res. 2020 May 21;48(9):5157-5168. doi: 10.1093/nar/gkaa227.
6
Mass spectrometry-based selectivity profiling identifies a highly selective inhibitor of the kinase MELK that delays mitotic entry in cancer cells.基于质谱的选择性分析鉴定出一种高度选择性的激酶 MELK 抑制剂，该抑制剂可延迟癌细胞有丝分裂的进入。
J Biol Chem. 2020 Feb 21;295(8):2359-2374. doi: 10.1074/jbc.RA119.011083. Epub 2020 Jan 2.
7
A Consensus Binding Motif for the PP4 Protein Phosphatase.PP4 蛋白磷酸酶的共识结合基序。
Mol Cell. 2019 Dec 19;76(6):953-964.e6. doi: 10.1016/j.molcel.2019.08.029. Epub 2019 Oct 1.
8
Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A.脱离有丝分裂：PP1 和 PP2A 对有丝分裂退出和胞质分裂的时空控制。
FEBS Lett. 2019 Oct;593(20):2908-2924. doi: 10.1002/1873-3468.13595. Epub 2019 Sep 18.
9
Chk1 KA1 domain auto-phosphorylation stimulates biological activity and is linked to rapid proteasomal degradation.Chk1KA1 结构域自动磷酸化刺激生物活性，并与快速蛋白酶体降解有关。
Sci Rep. 2018 Dec 3;8(1):17536. doi: 10.1038/s41598-018-35616-9.
10
Protein phosphatases in the regulation of mitosis.蛋白质磷酸酶在有丝分裂调控中的作用。
J Cell Biol. 2019 Feb 4;218(2):395-409. doi: 10.1083/jcb.201809138. Epub 2018 Nov 16.