RhoGEF17—An Essential Regulator of Endothelial Cell Death and Growth
| العنوان: | RhoGEF17—An Essential Regulator of Endothelial Cell Death and Growth |
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| المؤلفون: | Aline Jatho, Pamina Weber, Laura C Zelarayan, Doris Baltus, Thomas Wieland, Susanne Lutz, Oliver Drews |
| المصدر: | Cells Volume 10 Issue 4 Cells, Vol 10, Iss 741, p 741 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, adherens junction complex, Proteasome Endopeptidase Complex, Programmed cell death, Apoptosis, Models, Biological, Article, Adherens junction, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Animals, Guanine Nucleotide Exchange Factors, Humans, Phosphorylation, Cell adhesion, Protein kinase B, lcsh:QH301-705.5, beta Catenin, non-canonical β-catenin signaling, Cell Proliferation, Gene knockdown, Cell Death, Chemistry, Cell growth, Endothelial Cells, Adherens Junctions, Cell Cycle Checkpoints, General Medicine, Cell cycle, Rats, Cell biology, Endothelial stem cell, 030104 developmental biology, rho guanine nucleotide exchange factor, Gene Expression Regulation, lcsh:Biology (General), 030220 oncology & carcinogenesis, anchorage-dependent cell death, Proteolysis, endothelial cell |
| الوصف: | The Rho guanine nucleotide exchange factor RhoGEF17 was described to reside in adherens junctions (AJ) in endothelial cells (EC) and to play a critical role in the regulation of cell adhesion and barrier function. The purpose of this study was to analyze signal cascades and processes occurring subsequent to AJ disruption induced by RhoGEF17 knockdown. Primary human and immortalized rat EC were used to demonstrate that an adenoviral-mediated knockdown of RhoGEF17 resulted in cell rounding and an impairment in spheroid formation due to an enhanced proteasomal degradation of AJ components. In contrast, β-catenin degradation was impaired, which resulted in an induction of the β-catenin-target genes cyclin D1 and survivin. RhoGEF17 depletion additionally inhibited cell adhesion and sheet migration. The RhoGEF17 knockdown prevented the cells with impeded cell–cell and cell–matrix contacts from apoptosis, which was in line with a reduction in pro-caspase 3 expression and an increase in Akt phosphorylation. Nevertheless, the cells were not able to proliferate as a cell cycle block occurred. In summary, we demonstrate that a loss of RhoGEF17 disturbs cell–cell and cell–substrate interaction in EC. Moreover, it prevents the EC from cell death and blocks cell proliferation. Non-canonical β-catenin signaling and Akt activation could be identified as a potential mechanism. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| DOI: | 10.3390/cells10040741 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5bbc16892237014c95b5754abdd8ecbb |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5bbc16892237014c95b5754abdd8ecbb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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| DOI: | 10.3390/cells10040741 |