{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T01:39:43Z","timestamp":1775871583232,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T00:00:00Z","timestamp":1422316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP12239"],"award-info":[{"award-number":["GGP12239"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERA-Net Research Program on Rare Disease E-Rare-2","award":["Skindev"],"award-info":[{"award-number":["Skindev"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nectins are immunoglobulin\u2010like cell adhesion molecules mainly localized in adherens junctions. The transcription factor p63 is a master regulator of gene expression in stratified epithelia and controls several molecular processes. As mutations in the <jats:italic>Pvrl1<\/jats:italic> and <jats:italic>Pvrl4<\/jats:italic> genes encoding for nectins cause genetic disorders with phenotypes similar to <jats:italic>p63<\/jats:italic>\u2010related syndromes, we investigated whether these proteins might be under p63 transcriptional control. Here, we show that in <jats:italic>p63<\/jats:italic>\u2010null skin, <jats:italic>Pvrl1<\/jats:italic> gene expression is strongly reduced, whereas <jats:italic>Pvrl4<\/jats:italic> expression is unaffected. In human and mouse primary keratinocytes p63 depletion leads to a specific downregulation of the <jats:italic>Pvrl1<\/jats:italic> gene. Consistent with a direct regulation, chromatin immunoprecipitation experiments (ChIP) indicate that p63 binds to two conserved intronic <jats:italic>Pvrl1<\/jats:italic> enhancer regions. Ankyloblepharon\u2013ectodermal defects\u2013cleft lip\/palate (AEC) syndrome is a rare autosomal dominant disorder, caused by mutations in <jats:italic>p63<\/jats:italic> gene, mainly characterized by skin fragility. To test whether nectins may be affected in AEC syndrome, their expression was measured in keratinocytes obtained from patients with AEC or from a conditional mouse model for AEC syndrome. <jats:italic>Pvrl1<\/jats:italic> expression was reduced in AEC keratinocytes, consistent with impaired p63 function. Surprisingly, <jats:italic>Pvrl4<\/jats:italic> expression was similarly affected, in parallel with decreased expression of the transcription factor Irf6. Consistent with the well\u2010characterized role of Irf6 in keratinocyte differentiation and its strong downregulation in AEC syndrome, Irf6 depletion caused reduced expression of <jats:italic>Pvrl4<\/jats:italic> in wild\u2010type keratinocytes. Taken together, our results indicate that <jats:italic>Pvrl1<\/jats:italic> is a <jats:italic>bona fide<\/jats:italic> target gene of the transcription factor p63, whereas <jats:italic>Pvrl4<\/jats:italic> regulation is linked to epidermal differentiation and is under Irf6 control.<\/jats:p>","DOI":"10.1111\/exd.12593","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T07:23:13Z","timestamp":1415776993000},"page":"114-119","source":"Crossref","is-referenced-by-count":35,"title":["p63\u2010dependent and independent mechanisms of nectin\u20101 and nectin\u20104 regulation in the epidermis"],"prefix":"10.1111","volume":"24","author":[{"given":"Maria Rosaria","family":"Mollo","sequence":"first","affiliation":[{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II Napoli 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Dixon","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Human Sciences Manchester Academic Health Sciences Centre University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Brancati","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Aging Research Center Gabriele d'Annunzio University Chieti Italy"},{"name":"Medical Genetics Unit Policlinico Tor Vergata University Hospital Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Missero","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"},{"name":"Department of Biology University of Naples Federico II Napoli 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