دورية أكاديمية
The endothelial transcription factor ERG mediates Angiopoietin-1-dependent control of Notch signalling and vascular stability.
العنوان: | The endothelial transcription factor ERG mediates Angiopoietin-1-dependent control of Notch signalling and vascular stability. |
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المؤلفون: | Shah AV; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Birdsey GM; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Peghaire C; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Pitulescu ME; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Faculty of Medicine, University of Münster, D-48149 Münster, Germany., Dufton NP; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Yang Y; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Weinberg I; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Osuna Almagro L; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Payne L; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Mason JC; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK., Gerhardt H; Vascular Patterning Laboratory, Vesalius Research Center, VIB, KU Leuven, 3000 Leuven, Belgium &Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany., Adams RH; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Faculty of Medicine, University of Münster, D-48149 Münster, Germany., Randi AM; Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK. |
المصدر: | Nature communications [Nat Commun] 2017 Jul 11; Vol. 8, pp. 16002. Date of Electronic Publication: 2017 Jul 11. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Vascular Remodeling*, Angiopoietin-1/*metabolism , Receptors, Notch/*metabolism, Adaptor Proteins, Signal Transducing ; Animals ; Calcium-Binding Proteins ; Female ; Human Umbilical Vein Endothelial Cells ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Jagged-1 Protein/metabolism ; Male ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Transcriptional Regulator ERG/metabolism ; Wnt Signaling Pathway |
مستخلص: | Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation and stability. Here we identify the transcription factor ERG as a key regulator of endothelial Notch signalling. We show that ERG controls the balance between Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo, this regulation occurs selectively in the maturing plexus of the mouse developing retina, where Ang1/Tie2 signalling is active. We find that ERG mediates Ang1-dependent regulation of Notch ligands and is required for the stabilizing effects of Ang1 in vivo. We show that Ang1 induces ERG phosphorylation in a phosphoinositide 3-kinase (PI3K)/Akt-dependent manner, resulting in ERG enrichment at Dll4 promoter and multiple enhancers. Finally, we demonstrate that ERG directly interacts with Notch intracellular domain (NICD) and β-catenin and is required for Ang1-dependent β-catenin recruitment at the Dll4 locus. We propose that ERG coordinates Ang1, β-catenin and Notch signalling to promote vascular stability. |
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معلومات مُعتمدة: | PG/10/94/28651 United Kingdom BHF_ British Heart Foundation; RG/11/17/29256 United Kingdom BHF_ British Heart Foundation; RG/17/4/32662 United Kingdom BHF_ British Heart Foundation |
المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (Angiopoietin-1) 0 (Calcium-Binding Proteins) 0 (DLL4 protein, human) 0 (ERG protein, human) 0 (Intercellular Signaling Peptides and Proteins) 0 (JAG1 protein, human) 0 (Jagged-1 Protein) 0 (Receptors, Notch) 0 (Transcriptional Regulator ERG) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
تواريخ الأحداث: | Date Created: 20170712 Date Completed: 20181211 Latest Revision: 20210109 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5508205 |
DOI: | 10.1038/ncomms16002 |
PMID: | 28695891 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/ncomms16002 |