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dc.contributor | Facultad de Ciencias Biologicas y Ambientales | es_ES |
dc.contributor.author | Maeso Alonso, Laura | |
dc.contributor.author | Alonso-Olivares, Hugo | |
dc.contributor.author | Martínez-García, Nicole | |
dc.contributor.author | López-Ferreras, Lorena | |
dc.contributor.author | Villoch-Fernández, Javier | |
dc.contributor.author | Puente-Santamaría, Laura | |
dc.contributor.author | Colas-Algora, Natalia | |
dc.contributor.author | Fernández-Corona, Alfonso | |
dc.contributor.author | Lorenzo-Marcos, María Elena | |
dc.contributor.author | Jiménez, Benilde | |
dc.contributor.author | Holmgren, Lars | |
dc.contributor.author | Wilhelm, Margareta | |
dc.contributor.author | Millan, Jaime | |
dc.contributor.author | del Peso, Luis | |
dc.contributor.author | Claesson-Welsh, Lena | |
dc.contributor.author | Marqués Martínez, Margarita | |
dc.contributor.author | Marín Vieira, María Carmen | |
dc.contributor.other | Bioquimica y Biologia Molecular | es_ES |
dc.date | 2022 | |
dc.date.accessioned | 2022-10-04T10:22:40Z | |
dc.date.available | 2022-10-04T10:22:40Z | |
dc.identifier.citation | Maeso-Alonso, L., Alonso-Olivares, H., Martínez-García, N. et al. p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin. Cell. Mol. Life Sci. 79, 535 (2022). https://doi.org/10.1007/s00018-022-04560-3 | es_ES |
dc.identifier.issn | 1420-682X | |
dc.identifier.other | https://link.springer.com/article/10.1007/s00018-022-04560-3 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10612/15156 | |
dc.description.abstract | [EN] Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell–cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels. | es_ES |
dc.language | eng | es_ES |
dc.publisher | Springer | es_ES |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Biología | es_ES |
dc.subject.other | p53 family | es_ES |
dc.subject.other | Cell junctions | es_ES |
dc.subject.other | Endothelial barrier integrity | es_ES |
dc.subject.other | Vascular morphogenesis | es_ES |
dc.subject.other | Actin cytoskeleton | es_ES |
dc.subject.other | VE-cadherin and angiogenesis | es_ES |
dc.title | p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | 10.1007/s00018-022-04560-3 | |
dc.description.peerreviewed | SI | es_ES |
dc.relation.projectID | info: eu-repo/grantAgreement/AEI/Programa Estatal de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i/PID2019-105169RB-I00/ES/FUNCION DE P73 EN EL ADHESOMA CELULAR: IMPLICACIONES EN MORFOGENESIS VASCULAR, ANGIOGENESIS Y CANCER | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.essn | 1420-9071 | |
dc.journal.title | Cellular and Molecular Life Sciences | es_ES |
dc.volume.number | 79 | es_ES |
dc.issue.number | 10 | es_ES |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es_ES |
dc.subject.unesco | 2415 Biología Molecular | es_ES |
dc.audience.educationLevel | ||
dc.description.project | Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE | es_ES |
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