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By biochemical and imaging approaches, we demonstrate that EPS8 associates with the VE-cadherin complex of remodeling junctions promoting YAP translocation to the nucleus and transcriptional activation. Conversely, in stabilized junctions, 14\u20133-3\u2013YAP associates with the VE\u2013cadherin complex, whereas Eps8 is excluded. Junctional association of YAP inhibits nuclear translocation and inactivates its transcriptional activity both in vitro and in vivo in Eps8-null mice. The absence of Eps8 also increases vascular permeability in vivo, but did not induce other major vascular defects. Collectively, we identified novel components of the adherens junction complex, and we introduce a novel molecular mechanism through which the VE-cadherin complex controls YAP transcriptional activity.<\/jats:p>","DOI":"10.1083\/jcb.201501089","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T03:48:36Z","timestamp":1450151316000},"page":"1177-1192","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":79,"title":["The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling"],"prefix":"10.1083","volume":"211","author":[{"given":"Costanza","family":"Giampietro","sequence":"first","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"},{"name":"Dipartimento di Bioscienze, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Disanza","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Bravi","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Barrios-Rodiles","sequence":"additional","affiliation":[{"name":"Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Corada","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Frittoli","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Savorani","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Lampugnani","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"},{"name":"Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Boggetti","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases, Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carien","family":"Niessen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases, Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff L.","family":"Wrana","sequence":"additional","affiliation":[{"name":"Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada 2"},{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Scita","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"},{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Dejana","sequence":"additional","affiliation":[{"name":"FIRC Institute of Molecular Oncology, 20139 Milan, Italy 1"},{"name":"Dipartimento di Bioscienze, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy 6"},{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 05 Uppsala, Sweden 8"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,12,14]]},"reference":[{"key":"2023072308135085200_bib1","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.cell.2013.07.042","article-title":"A mechanical checkpoint controls multicellular growth through YAP\/TAZ regulation by actin-processing factors","volume":"154","author":"Aragona","year":"2013","journal-title":"Cell."},{"key":"2023072308135085200_bib2","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1242\/jcs.116228","article-title":"Regulation of fibroblast growth factor receptor signalling and trafficking by Src and Eps8","volume":"126","author":"Auciello","year":"2013","journal-title":"J. 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