非经典 Notch 信号通路：作用与机制的新发现
Non-canonical Notch signaling: emerging role and mechanism.
机构信息
Division of Cardiology, Department of Medicine, Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21205, USA.
出版信息
Trends Cell Biol. 2012 May;22(5):257-65. doi: 10.1016/j.tcb.2012.02.003. Epub 2012 Mar 5.
Abstract
Notch is an ancient transmembrane receptor with crucial roles in cell-fate choices. Although the 'canonical' Notch pathway and its core members are well established - involving ligand-induced cleavage of Notch for transcriptional regulation - it has been unclear whether Notch can also function independently of ligand and transcription ('non-canonically') through a common mechanism. Recent studies suggest that Notch can non-canonically exert its biological functions by post-translationally targeting Wnt/β-catenin signaling, an important cellular and developmental regulator. The non-canonical Notch pathway appears to be highly conserved from flies to mammals. Here, we discuss the emerging conserved mechanism and role of ligand/transcription-independent Notch signaling in cell and developmental biology.
摘要
Notch 是一种古老的跨膜受体，在细胞命运选择中起着至关重要的作用。尽管“经典”Notch 途径及其核心成员已经得到充分证实——涉及配体诱导的 Notch 切割以进行转录调控——但 Notch 是否也可以通过共同的机制独立于配体和转录（“非经典”）发挥作用尚不清楚。最近的研究表明，Notch 可以通过翻译后靶向 Wnt/β-catenin 信号转导来发挥其生物学功能，Wnt/β-catenin 信号转导是一种重要的细胞和发育调节剂。非经典 Notch 途径似乎在从苍蝇到哺乳动物的过程中高度保守。在这里，我们讨论了配体/转录非依赖性 Notch 信号在细胞和发育生物学中的新兴保守机制和作用。
相似文献
1
Non-canonical Notch signaling: emerging role and mechanism.非经典 Notch 信号通路：作用与机制的新发现
Trends Cell Biol. 2012 May;22(5):257-65. doi: 10.1016/j.tcb.2012.02.003. Epub 2012 Mar 5.
2
Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately.Wnt和Notch信号通路分别通过靶向c-Myc和Hes1参与伤口愈合。
Stem Cell Res Ther. 2015 Jun 16;6(1):120. doi: 10.1186/s13287-015-0103-4.
3
Study of the aqueous extract of Aloe vera and its two active components on the Wnt/β-catenin and Notch signaling pathways in colorectal cancer cells.研究芦荟的水提物及其两种活性成分对结直肠癌细胞中 Wnt/β-catenin 和 Notch 信号通路的影响。
J Ethnopharmacol. 2019 Oct 28;243:112092. doi: 10.1016/j.jep.2019.112092. Epub 2019 Jul 15.
4
Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.Jagged1是结直肠癌中Wnt和Notch信号通路之间的病理联系。
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6315-20. doi: 10.1073/pnas.0813221106. Epub 2009 Mar 26.
5
Androgens up-regulate transcription of the Notch inhibitor Numb in C2C12 myoblasts via Wnt/β-catenin signaling to T cell factor elements in the Numb promoter.雄激素通过 Wnt/β-catenin 信号通路上调 C2C12 成肌细胞中 Notch 抑制剂 Numb 的转录，从而激活 Numb 启动子中的 T 细胞因子元件。
J Biol Chem. 2013 Jun 21;288(25):17990-8. doi: 10.1074/jbc.M113.478487. Epub 2013 May 6.
6
The Notch-2 gene is regulated by Wnt signaling in cultured colorectal cancer cells.Notch-2 基因受培养的结直肠癌细胞中的 Wnt 信号调控。
PLoS One. 2011 Mar 18;6(3):e17957. doi: 10.1371/journal.pone.0017957.
7
Canonical and non-canonical Wnt signaling are simultaneously activated by Wnts in colon cancer cells.在结肠癌细胞中，Wnt可同时激活经典和非经典Wnt信号通路。
Cell Signal. 2020 Aug;72:109636. doi: 10.1016/j.cellsig.2020.109636. Epub 2020 Apr 10.
8
The wnt target jagged-1 mediates the activation of notch signaling by progastrin in human colorectal cancer cells.Wnt靶基因锯齿状蛋白1介导胃泌素原在人结肠癌细胞中激活Notch信号通路。
Cancer Res. 2009 Aug 1;69(15):6065-73. doi: 10.1158/0008-5472.CAN-08-2409. Epub 2009 Jul 21.
9
Expression of Wnt and Notch signaling pathways in inflammatory bowel disease treated with mesenchymal stem cell transplantation: evaluation in a rat model.间充质干细胞移植治疗炎症性肠病中Wnt和Notch信号通路的表达：大鼠模型评估
Stem Cell Res Ther. 2015 May 22;6(1):101. doi: 10.1186/s13287-015-0092-3.
10
NUMB is a break of WNT-Notch signaling cycle.NUMB是WNT-Notch信号通路循环的一个断点。
Int J Mol Med. 2006 Sep;18(3):517-21.
引用本文的文献
1
Sarcopenia: Current Insights into Molecular Mechanisms, Diagnostics, and Emerging Interventional Approaches.肌肉减少症：对分子机制、诊断及新兴干预方法的当前见解
Int J Mol Sci. 2025 Jul 14;26(14):6740. doi: 10.3390/ijms26146740.
2
DTX1 Modulates Microglial M1 Polarization and Exacerbates Neuroinflammation in Traumatic Brain Injury Model Rats through NF-κB/IRF5.DTX1通过NF-κB/IRF5调节创伤性脑损伤模型大鼠的小胶质细胞M1极化并加剧神经炎症。
Mol Neurobiol. 2025 Jul 15. doi: 10.1007/s12035-025-05200-0.
3
The Notch pathway in Metazoa: a comparative analysis across cnidarians and beyond.后生动物中的Notch信号通路：刺胞动物及其他生物的比较分析
Evodevo. 2025 Jun 14;16(1):8. doi: 10.1186/s13227-025-00246-6.
4
Significance of Notch Signaling in Salivary Gland Development and Diseases.Notch信号通路在唾液腺发育及疾病中的意义
J Clin Med. 2025 May 10;14(10):3325. doi: 10.3390/jcm14103325.
5
Role of the Notch signaling pathway in porcine oocyte maturation.Notch信号通路在猪卵母细胞成熟中的作用。
Cell Commun Signal. 2025 Jan 2;23(1):1. doi: 10.1186/s12964-024-01996-x.
6
Dynamics of Endothelial Cell Diversity and Plasticity in Health and Disease.内皮细胞多样性和可塑性在健康和疾病中的动态变化。
Cells. 2024 Jul 29;13(15):1276. doi: 10.3390/cells13151276.
7
Notch signaling pathway in cancer: from mechanistic insights to targeted therapies. Notch 信号通路与癌症：从机制研究到靶向治疗。
Signal Transduct Target Ther. 2024 May 27;9(1):128. doi: 10.1038/s41392-024-01828-x.
8
Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Notch信号通路在胶质母细胞瘤恶性进展中的机制及靶向治疗
Biomolecules. 2024 Apr 15;14(4):480. doi: 10.3390/biom14040480.
9
Analysis of Genetic Diversity in Adzuki Beans (): Insights into Environmental Adaptation and Early Breeding Strategies for Yield Improvement.小豆的遗传多样性分析：对环境适应性及早期产量改良育种策略的见解
Plants (Basel). 2023 Dec 13;12(24):4154. doi: 10.3390/plants12244154.
10
Increased Expression of NOTCH-1 and T Helper Cell Transcription Factors in Patients with Acquired Aplastic Anemia.NOTCH-1 和辅助性 T 细胞转录因子在获得性再生障碍性贫血患者中的表达增加。
Iran Biomed J. 2023 Nov 1;27(6):357-65. doi: 10.61186/ibj.3754. Epub 2022 Jul 31.
本文引用的文献
1
Notch post-translationally regulates β-catenin protein in stem and progenitor cells.Notch 在后翻译水平上调节干细胞和祖细胞中的β-catenin 蛋白。
Nat Cell Biol. 2011 Aug 14;13(10):1244-51. doi: 10.1038/ncb2313.
2
Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells.Notch 与 Hif-α在果蝇血细胞发育和存活中的相互作用。
Science. 2011 Jun 3;332(6034):1210-3. doi: 10.1126/science.1199643.
3
Notch destabilises maternal beta-catenin and restricts dorsal-anterior development in Xenopus.Notch 使母本β-连环蛋白失稳，并限制 Xenopus 的背-前发育。
Development. 2011 Jun;138(12):2567-79. doi: 10.1242/dev.061143.
4
Modulation of the ligand-independent traffic of Notch by Axin and Apc contributes to the activation of Armadillo in Drosophila.Axin 和 Apc 对 Notch 配体非依赖性运输的调节有助于 Armadillo 在果蝇中的激活。
Development. 2011 Apr;138(8):1501-6. doi: 10.1242/dev.061309. Epub 2011 Mar 9.
5
Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma.Notch1 在 K-ras 诱导的胰腺导管腺癌模型中作为肿瘤抑制因子发挥作用。
Cancer Res. 2010 Jun 1;70(11):4280-6. doi: 10.1158/0008-5472.CAN-09-4645. Epub 2010 May 18.
6
Convergence of Notch and beta-catenin signaling induces arterial fate in vascular progenitors.Notch 和β-catenin 信号的收敛诱导血管祖细胞中的动脉命运。
J Cell Biol. 2010 Apr 19;189(2):325-38. doi: 10.1083/jcb.200904114.
7
A role of receptor Notch in ligand cis-inhibition in Drosophila.受体 Notch 在果蝇配体顺式抑制中的作用。
Curr Biol. 2010 Mar 23;20(6):554-60. doi: 10.1016/j.cub.2010.01.058. Epub 2010 Mar 11.
8
Ligand-independent traffic of Notch buffers activated Armadillo in Drosophila.Notch的不依赖配体的转运调节果蝇中被激活的犰狳蛋白。
PLoS Biol. 2009 Aug;7(8):e1000169. doi: 10.1371/journal.pbio.1000169. Epub 2009 Aug 11.
9
A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.一条涉及Notch1/β-连环蛋白/Isl1的调控通路决定心脏祖细胞的命运。
Nat Cell Biol. 2009 Aug;11(8):951-7. doi: 10.1038/ncb1906. Epub 2009 Jul 20.
10
Numb regulates post-endocytic trafficking and degradation of Notch1.Numb调节Notch1的内吞后运输和降解。
J Biol Chem. 2009 Sep 25;284(39):26427-38. doi: 10.1074/jbc.M109.014845. Epub 2009 Jun 30.
Zotero 插件