{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:02:34Z","timestamp":1790175754672,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30-ES006096"],"award-info":[{"award-number":["P30-ES006096"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Damage\u2010induced long noncoding RNA (DINO) is a long noncoding RNA that directly interacts with p53 and thereby enhances p53 stability and activity in response to various cellular stresses. Here, we demonstrate that nuclear receptor subfamily 2 group E member 3 (NR2E3) plays a crucial role in maintaining active DINO epigenetic status for its proper induction and subsequent p53 activation. In acetaminophen (APAP)\u2010 or carbon tetrachloride\u2010induced acute liver injuries, NR2E3 knockout (KO) mice exhibited far more severe liver injuries due to impaired DINO induction and p53 activation. Mechanistically, NR2E3 loss both\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    induced epigenetic DINO repression accompanied by reduced DINO chromatin accessibility. Furthermore, compared with the efficient reversal by a typical antidote N\u2010acetylcysteine (NAC) treatment of APAP\u2010induced liver injury in wild\u2010type mice, the liver injury of NR2E3 KO mice was not effectively reversed, indicating that an intact NR2E3\u2010DINO\u2010p53\u2013signaling axis is essential for NAC\u2010mediated recovery against APAP\u2010induced hepatotoxicity. These findings establish that NR2E3 is a critical component in p53 activation and a novel susceptibility factor to drug\u2010 or toxicant\u2010induced acute liver injuries.\u2014Khanal, T., Leung, Y.\u2010K., Jiang, W., Timchenko, N., Ho, S.\u2010M., Kim, K. NR2E3 is a key component in p53 activation by regulating a long noncoding RNA DINO in acute liver injuries. FASEB J. 33, 8335\u20138348 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801881rr","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T19:32:26Z","timestamp":1555443146000},"page":"8335-8348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["NR2E3 is a key component in p53 activation by regulating a long noncoding RNA DINO in acute liver injuries"],"prefix":"10.1096","volume":"33","author":[{"given":"Tilak","family":"Khanal","sequence":"first","affiliation":[{"name":"Department of Environmental Health College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuet-Kin","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Environmental Health College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Timchenko","sequence":"additional","affiliation":[{"name":"Division of Pediatric General and Thoracic Surgery Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuk-Mei","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Environmental Health College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyounghyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Environmental Health College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2011.12.002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.05.031"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1218351"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3673"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/72777"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022533099"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100187"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.06.1708"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"10662","DOI":"10.1038\/s41598-017-11106-2","article-title":"Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer","volume":"7","author":"Khanal T.","year":"2017","journal-title":"Sci. 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