{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:21:28Z","timestamp":1773746488936,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1366, CRC 1002"],"award-info":[{"award-number":["CRC 1366, CRC 1002"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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, \u03b2-catenin degradation was impaired, which resulted in an induction of the \u03b2-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\u2013cell and cell\u2013matrix 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\u2013cell and cell\u2013substrate interaction in EC. Moreover, it prevents the EC from cell death and blocks cell proliferation. Non-canonical \u03b2-catenin signaling and Akt activation could be identified as a potential mechanism.<\/jats:p>","DOI":"10.3390\/cells10040741","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T22:09:01Z","timestamp":1616969341000},"page":"741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["RhoGEF17\u2014An Essential Regulator of Endothelial Cell Death and Growth"],"prefix":"10.3390","volume":"10","author":[{"given":"Pamina","family":"Weber","sequence":"first","affiliation":[{"name":"Experimental Pharmacology Mannheim (EPM), European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doris","family":"Baltus","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Mannheim (EPM), European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Jatho","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medical Center G\u00f6ttingen, Robert-Koch-Strasse 40, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Drews","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura C.","family":"Zelarayan","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medical Center G\u00f6ttingen, Robert-Koch-Strasse 40, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8262-8261","authenticated-orcid":false,"given":"Thomas","family":"Wieland","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Mannheim (EPM), European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg\/Mannheim, Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Lutz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medical Center G\u00f6ttingen, Robert-Koch-Strasse 40, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Center for Cardiovascular Research) Partner Site G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.devcel.2013.08.020","article-title":"VE-cadherin and endothelial adherens junctions: Active guardians of vascular integrity","volume":"26","author":"Giannotta","year":"2013","journal-title":"Dev. 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