EMT 转录因子的蛋白质稳定性调控。
Regulation of the protein stability of EMT transcription factors.
机构信息
a Programa de Recerca en Càncer ; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM); Parc de Recerca Biomèdica de Barcelona; Doctor Aiguader; Barcelona, Spain.
出版信息
Cell Adh Migr. 2014;8(4):418-28. doi: 10.4161/19336918.2014.969998.
Abstract
The epithelial to mesenchymal transition (EMT) consists of a rapid change of cell phenotype, characterized by the loss of epithelial characteristics and the acquisition of a more invasive phenotype. Transcription factors regulating EMT (Snail, Twist and Zeb) are extremely labile proteins, rapidly degraded by the proteasome system. In this review we analyze the current mechanisms controlling degradation of EMT transcription factors, focusing on the role of new E3 ubiquitin-ligases involved in EMT. We also summarize the regulation of the stability of these EMT transcription factors, specially observed in different stress conditions, such as hypoxia, chemotherapeutic drugs, oxidative stress or γ-irradiation.
摘要
上皮间质转化（EMT）包括细胞表型的快速变化，其特征是上皮特征的丧失和更具侵袭性表型的获得。调节 EMT 的转录因子（Snail、Twist 和 Zeb）是极不稳定的蛋白质，可被蛋白酶体系统迅速降解。在这篇综述中，我们分析了目前控制 EMT 转录因子降解的机制，重点关注了新的 EMT 参与的 E3 泛素连接酶的作用。我们还总结了这些 EMT 转录因子稳定性的调节，特别是在不同的应激条件下，如缺氧、化疗药物、氧化应激或 γ 辐射下的调节。
相似文献
1
Regulation of the protein stability of EMT transcription factors.EMT 转录因子的蛋白质稳定性调控。
Cell Adh Migr. 2014;8(4):418-28. doi: 10.4161/19336918.2014.969998.
2
Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing transcription factors.非典型泛素E3连接酶复合物Skp1-Pam-Fbxo45调控核心上皮-间质转化诱导转录因子。
Oncotarget. 2015 Jan 20;6(2):979-94. doi: 10.18632/oncotarget.2825.
3
F-box proteins: Keeping the epithelial-to-mesenchymal transition (EMT) in check.F-box蛋白：控制上皮-间质转化（EMT）
Semin Cancer Biol. 2016 Feb;36:71-9. doi: 10.1016/j.semcancer.2015.10.003. Epub 2015 Nov 11.
4
Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer.E3泛素连接酶和去泛素化酶对癌症中上皮-间质转化的调控
Curr Cancer Drug Targets. 2016;16(2):110-8. doi: 10.2174/1568009616666151112122126.
5
Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics.蜗牛 1 诱导上皮间质转化和肿瘤起始干细胞特征。
BMC Cancer. 2011 Sep 19;11:396. doi: 10.1186/1471-2407-11-396.
6
The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation.缺氧调控的 FBXL14 泛素连接酶将 SNAIL1 作为靶标进行蛋白酶体降解。
J Biol Chem. 2010 Feb 5;285(6):3794-3805. doi: 10.1074/jbc.M109.065995. Epub 2009 Dec 2.
7
Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability.FBXL5 通过核泛素化调节 Snail1 的 DNA 结合和稳定性。
Nucleic Acids Res. 2014 Jan;42(2):1079-94. doi: 10.1093/nar/gkt935. Epub 2013 Oct 23.
8
The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1.F -box 蛋白 Ppa 是核心 EMT 因子 Twist、Snail、Slug 和 Sip1 的共同调节因子。
J Cell Biol. 2011 Jul 11;194(1):17-25. doi: 10.1083/jcb.201012085. Epub 2011 Jul 4.
9
MiR-195 inhibits the ubiquitination and degradation of YY1 by Smurf2, and induces EMT and cell permeability of retinal pigment epithelial cells.miR-195 通过 Smurf2 抑制 YY1 的泛素化和降解，并诱导视网膜色素上皮细胞的 EMT 和细胞通透性。
Cell Death Dis. 2021 Jul 15;12(7):708. doi: 10.1038/s41419-021-03956-6.
10
Multilayer control of the EMT master regulators.EMT 主调控因子的多层级控制。
Oncogene. 2014 Apr 3;33(14):1755-63. doi: 10.1038/onc.2013.128. Epub 2013 Apr 22.
引用本文的文献
1
HOPX regulates the invasion and migration abilities of hepatocellular carcinoma by targeting SNAIL.HOPX通过靶向SNAIL调节肝细胞癌的侵袭和迁移能力。
Sci Rep. 2025 Aug 13;15(1):29739. doi: 10.1038/s41598-025-15581-w.
2
A human model of radiation-induced skin injury reveals p53-driven DNA damage signaling and recapitulates a TGFβ fibrotic response.辐射诱导皮肤损伤的人体模型揭示了p53驱动的DNA损伤信号传导，并重现了TGFβ纤维化反应。
bioRxiv. 2025 Jun 8:2025.06.04.657901. doi: 10.1101/2025.06.04.657901.
3
Targeting epithelial-mesenchymal transition signaling pathways with Dietary Phytocompounds and repurposed drug combinations for overcoming drug resistance in various cancers.利用膳食植物化合物和重新利用的药物组合靶向上皮-间质转化信号通路以克服各种癌症中的耐药性。
Heliyon. 2025 Jan 23;11(3):e41964. doi: 10.1016/j.heliyon.2025.e41964. eCollection 2025 Feb 15.
4
Identification of R2R3-MYB Transcription Factor Family Based on Genome and Promoting Betalain Biosynthesis by Directly Activating Expression.基于基因组鉴定R2R3-MYB转录因子家族并通过直接激活表达促进甜菜红素生物合成
Plants (Basel). 2025 Jan 22;14(3):324. doi: 10.3390/plants14030324.
5
Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.非小细胞肺癌图谱与分析：探索相互关联的致癌信号整合因子
Mamm Genome. 2025 Feb 12. doi: 10.1007/s00335-025-10110-6.
6
The Scribble-SGEF-Dlg1 complex regulates E-cadherin and ZO-1 stability, turnover and transcription in epithelial cells.Scribble-SGEF-Dlg1 复合物调节上皮细胞中 E-钙黏蛋白和 ZO-1 的稳定性、周转率和转录。
J Cell Sci. 2024 Oct 1;137(19). doi: 10.1242/jcs.262181. Epub 2024 Oct 14.
7
Factors Determining Epithelial-Mesenchymal Transition in Cancer Progression.影响癌症进展中上皮-间充质转化的因素。
Int J Mol Sci. 2024 Aug 17;25(16):8972. doi: 10.3390/ijms25168972.
8
PP2A B55α inhibits epithelial-mesenchymal transition via regulation of Slug expression in non-small cell lung cancer.PP2A B55α 通过调节非小细胞肺癌中 Slug 的表达抑制上皮-间充质转化。
Cancer Lett. 2024 Aug 28;598:217110. doi: 10.1016/j.canlet.2024.217110. Epub 2024 Jul 8.
9
Prognostic value of RNF113A shows a correlation with immune infiltrates in colorectal cancer.RNF113A的预后价值显示出与结直肠癌中的免疫浸润相关。
Am J Transl Res. 2024 Apr 15;16(4):1281-1294. doi: 10.62347/EUKS9325. eCollection 2024.
10
Dynamics of Single-Cell Protein Covariation during Epithelial-Mesenchymal Transition.上皮-间质转化过程中单细胞蛋白质共变的动力学
J Proteome Res. 2025 Apr 4;24(4):1519-1527. doi: 10.1021/acs.jproteome.4c00277. Epub 2024 Apr 25.
本文引用的文献
1
HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism.HERC2 通过靶向铁调节蛋白 FBXL5 进行降解来调节铁代谢。
J Biol Chem. 2014 Jun 6;289(23):16430-41. doi: 10.1074/jbc.M113.541490. Epub 2014 Apr 28.
2
Roles of F-box proteins in cancer.F -box 蛋白在癌症中的作用。
Nat Rev Cancer. 2014 Apr;14(4):233-47. doi: 10.1038/nrc3700.
3
Molecular mechanisms of epithelial-mesenchymal transition.上皮-间质转化的分子机制。
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96. doi: 10.1038/nrm3758.
4
Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigenesis in basal-like breast cancer.破坏 BRD4 与乙酰化 Twist 的相互作用可抑制基底样乳腺癌的肿瘤发生。
Cancer Cell. 2014 Feb 10;25(2):210-25. doi: 10.1016/j.ccr.2014.01.028.
5
The roles of HLH transcription factors in epithelial mesenchymal transition and multiple molecular mechanisms.HLH 转录因子在上皮间质转化和多种分子机制中的作用。
Clin Exp Metastasis. 2014 Mar;31(3):367-77. doi: 10.1007/s10585-013-9621-6. Epub 2013 Oct 26.
6
Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability.FBXL5 通过核泛素化调节 Snail1 的 DNA 结合和稳定性。
Nucleic Acids Res. 2014 Jan;42(2):1079-94. doi: 10.1093/nar/gkt935. Epub 2013 Oct 23.
7
The malignant brain tumor (MBT) domain protein SFMBT1 is an integral histone reader subunit of the LSD1 demethylase complex for chromatin association and epithelial-to-mesenchymal transition.恶性脑肿瘤（MBT）结构域蛋白 SFMBT1 是 LSD1 去甲基化酶复合物的一个完整的组蛋白读取亚基，用于染色质结合和上皮-间充质转化。
J Biol Chem. 2013 Sep 20;288(38):27680-27691. doi: 10.1074/jbc.M113.482349. Epub 2013 Aug 8.
8
GSK3β controls epithelial-mesenchymal transition and tumor metastasis by CHIP-mediated degradation of Slug.GSK3β 通过 CHIP 介导的 Slug 降解来控制上皮-间质转化和肿瘤转移。
Oncogene. 2014 Jun 12;33(24):3172-82. doi: 10.1038/onc.2013.279. Epub 2013 Jul 15.
9
DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail.DYRK2 通过降解 Snail 来控制乳腺癌中的上皮-间充质转化。
Cancer Lett. 2013 Oct 10;339(2):214-25. doi: 10.1016/j.canlet.2013.06.005. Epub 2013 Jun 18.
10
Mechanisms and function of substrate recruitment by F-box proteins.F-box 蛋白募集底物的机制和功能。
Nat Rev Mol Cell Biol. 2013 Jun;14(6):369-81. doi: 10.1038/nrm3582. Epub 2013 May 9.
Zotero 插件