{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:18:09Z","timestamp":1791001089194,"version":"4.1.0"},"reference-count":50,"publisher":"Elsevier BV","issue":"49","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":256,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK084567"],"award-info":[{"award-number":["P30DK084567"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK57993"],"award-info":[{"award-number":["DK57993"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1074\/jbc.ra119.010176","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T02:45:19Z","timestamp":1572317119000},"page":"18698-18713","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":35,"title":["The transcription factor ETS1 promotes apoptosis resistance of senescent cholangiocytes by epigenetically up-regulating the apoptosis suppressor BCL2L1"],"prefix":"10.1016","volume":"294","author":[{"given":"Steven P.","family":"O'Hara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick L.","family":"Splinter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy E.","family":"Trussoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Guicciardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah P.","family":"Splinter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S.","family":"Al Suraih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navine","family":"Nasser-Ghodsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Stollenwerk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Gores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas F.","family":"LaRusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1074\/jbc.RA119.010176_bib1","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1056\/NEJMra1506330","article-title":"Primary sclerosing cholangitis","volume":"375","author":"Lazaridis","year":"2016","journal-title":"N. Engl. J. Med"},{"key":"10.1074\/jbc.RA119.010176_bib2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1586\/egh.12.80","article-title":"Primary sclerosing cholangitis: a review and update on therapeutic developments","volume":"7","author":"Tabibian","year":"2013","journal-title":"Expert Rev. Gastroenterol. Hepatol"},{"key":"10.1074\/jbc.RA119.010176_bib3","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/0016-5085(91)90673-9","article-title":"Natural history and prognostic variables in primary sclerosing cholangitis","volume":"100","author":"Farrant","year":"1991","journal-title":"Gastroenterology"},{"key":"10.1074\/jbc.RA119.010176_bib4","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: when bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"10.1074\/jbc.RA119.010176_bib5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.18632\/aging.100467","article-title":"Replicatively senescent cells are arrested in G1 and G2 phases","volume":"4","author":"Mao","year":"2012","journal-title":"Aging (Albany, NY)"},{"key":"10.1074\/jbc.RA119.010176_bib6","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1056\/NEJMoa066157","article-title":"Telomerase mutations in families with idiopathic pulmonary fibrosis","volume":"356","author":"Armanios","year":"2007","journal-title":"N. Engl. J. Med"},{"key":"10.1074\/jbc.RA119.010176_bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11357-008-9075-y","article-title":"Cellular senescence, ageing and disease","volume":"31","author":"Burton","year":"2009","journal-title":"Age (Dordr)"},{"key":"10.1074\/jbc.RA119.010176_bib8","doi-asserted-by":"crossref","first-page":"231ra247","DOI":"10.1126\/scitranslmed.3008182","article-title":"Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance","volume":"6","author":"Hecker","year":"2014","journal-title":"Sci. Transl. Med"},{"key":"10.1074\/jbc.RA119.010176_bib9","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1474-9726.2010.00608.x","article-title":"Fat tissue, aging, and cellular senescence","volume":"9","author":"Tchkonia","year":"2010","journal-title":"Aging Cell"},{"key":"10.1074\/jbc.RA119.010176_bib10","doi-asserted-by":"crossref","first-page":"14532","DOI":"10.1038\/ncomms14532","article-title":"Cellular senescence mediates fibrotic pulmonary disease","volume":"8","author":"Schafer","year":"2017","journal-title":"Nat. Commun"},{"key":"10.1074\/jbc.RA119.010176_bib11","doi-asserted-by":"crossref","first-page":"e100492","DOI":"10.15252\/embj.2018100492","article-title":"Length-independent telomere damage drives post-mitotic cardiomyocyte senescence","volume":"38","author":"Anderson","year":"2019","journal-title":"EMBO J"},{"key":"10.1074\/jbc.RA119.010176_bib12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.mad.2008.04.001","article-title":"Cellular senescence and organismal aging","volume":"129","author":"Jeyapalan","year":"2008","journal-title":"Mech. Ageing Dev"},{"key":"10.1074\/jbc.RA119.010176_bib13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ebiom.2017.03.027","article-title":"Telomeres and cell senescence: size matters not","volume":"21","author":"Victorelli","year":"2017","journal-title":"EBioMedicine"},{"key":"10.1074\/jbc.RA119.010176_bib14","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1002\/hep.26993","article-title":"Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis","volume":"59","author":"Tabibian","year":"2014","journal-title":"Hepatology"},{"key":"10.1074\/jbc.RA119.010176_bib15","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1371\/journal.pbio.0060301","article-title":"Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor","volume":"6","author":"Copp\u00e9","year":"2008","journal-title":"PLos Biol"},{"key":"10.1074\/jbc.RA119.010176_bib16","doi-asserted-by":"crossref","first-page":"30352","DOI":"10.1074\/jbc.M111.269464","article-title":"Cholangiocyte N-Ras protein mediates lipopolysaccharide-induced interleukin 6 secretion and proliferation","volume":"286","author":"O'Hara","year":"2011","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA119.010176_bib17","doi-asserted-by":"crossref","first-page":"e0125793","DOI":"10.1371\/journal.pone.0125793","article-title":"Lipopolysaccharide (LPS)-induced biliary epithelial cell NRas activation requires epidermal growth factor receptor (EGFR)","volume":"10","author":"Trussoni","year":"2015","journal-title":"PLoS ONE"},{"key":"10.1074\/jbc.RA119.010176_bib18","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1074\/jbc.M117.777409","article-title":"ETS proto-oncogene 1 transcriptionally up-regulates the cholangiocyte senescence-associated protein cyclin-dependent kinase inhibitor 2A","volume":"292","author":"O'Hara","year":"2017","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA119.010176_bib19","first-page":"2284","article-title":"Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved","volume":"55","author":"Wang","year":"1995","journal-title":"Cancer Res"},{"key":"10.1074\/jbc.RA119.010176_bib20","doi-asserted-by":"crossref","first-page":"11190","DOI":"10.1038\/ncomms11190","article-title":"Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL","volume":"7","author":"Yosef","year":"2016","journal-title":"Nat. Commun"},{"key":"10.1074\/jbc.RA119.010176_bib21","doi-asserted-by":"crossref","first-page":"955","DOI":"10.18632\/aging.101202","article-title":"New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463","volume":"9","author":"Zhu","year":"2017","journal-title":"Aging (Albany, NY)"},{"key":"10.1074\/jbc.RA119.010176_bib22","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.coi.2007.05.004","article-title":"Bcl-2-regulated apoptosis: mechanism and therapeutic potential","volume":"19","author":"Adams","year":"2007","journal-title":"Curr. Opin. Immunol"},{"key":"10.1074\/jbc.RA119.010176_bib23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-genet-102108-134850","article-title":"The role of mitochondria in apoptosis","volume":"43","author":"Wang","year":"2009","journal-title":"Annu. Rev. Genet"},{"key":"10.1074\/jbc.RA119.010176_bib24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/hep.29464","article-title":"Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2(\u2212\/\u2212)) mice","volume":"67","author":"Moncsek","year":"2018","journal-title":"Hepatology"},{"key":"10.1074\/jbc.RA119.010176_bib25","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/sj.onc.1203385","article-title":"EAP1\/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes","volume":"19","author":"Li","year":"2000","journal-title":"Oncogene"},{"key":"10.1074\/jbc.RA119.010176_bib26","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.ygyno.2007.05.024","article-title":"Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-1-A cells","volume":"106","author":"Yu","year":"2007","journal-title":"Gynecol. Oncol"},{"key":"10.1074\/jbc.RA119.010176_bib27","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/cphy.c120020","article-title":"Apoptosis and necrosis in the liver","volume":"3","author":"Guicciardi","year":"2013","journal-title":"Compr. Physiol"},{"key":"10.1074\/jbc.RA119.010176_bib28","doi-asserted-by":"crossref","first-page":"e18330","DOI":"10.1371\/journal.pone.0018330","article-title":"Hedgehog inhibition promotes a switch from type II to type I cell death receptor signaling in cancer cells","volume":"6","author":"Kurita","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1074\/jbc.RA119.010176_bib29","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/cdd.2017.186","article-title":"BCL-2 family proteins: changing partners in the dance towards death","volume":"25","author":"Kale","year":"2018","journal-title":"Cell Death Differ"},{"key":"10.1074\/jbc.RA119.010176_bib30","doi-asserted-by":"crossref","first-page":"D670","DOI":"10.1093\/nar\/gku1177","article-title":"The UCSC genome browser database: 2015 update","volume":"43","author":"Rosenbloom","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"10.1074\/jbc.RA119.010176_bib31","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res"},{"key":"10.1074\/jbc.RA119.010176_bib32","first-page":"656","article-title":"BLAT: the BLAST-like alignment tool","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res"},{"key":"10.1074\/jbc.RA119.010176_bib33","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/emboj.2010.106","article-title":"Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo","volume":"29","author":"Wei","year":"2010","journal-title":"EMBO J"},{"key":"10.1074\/jbc.RA119.010176_bib34","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.bbrc.2008.10.053","article-title":"Epiregulin expression by Ets-1 and ERK signaling pathway in Ki-ras-transformed cells","volume":"377","author":"Cho","year":"2008","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"10.1074\/jbc.RA119.010176_bib35","doi-asserted-by":"crossref","first-page":"154","DOI":"10.4161\/sgtp.19630","article-title":"RAS\/ERK pathway transcriptional regulation through ETS\/AP-1 binding sites","volume":"3","author":"Hollenhorst","year":"2012","journal-title":"Small GTPases"},{"key":"10.1074\/jbc.RA119.010176_bib36","doi-asserted-by":"crossref","first-page":"11928","DOI":"10.1093\/nar\/gku929","article-title":"ETS1 is a genome-wide effector of RAS\/ERK signaling in epithelial cells","volume":"42","author":"Plotnik","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"10.1074\/jbc.RA119.010176_bib37","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/35059131","article-title":"Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence","volume":"409","author":"Ohtani","year":"2001","journal-title":"Nature"},{"key":"10.1074\/jbc.RA119.010176_bib38","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.cell.2013.10.019","article-title":"Programmed cell senescence during mammalian embryonic development","volume":"155","author":"Mu\u00f1oz-Espin","year":"2013","journal-title":"Cell"},{"key":"10.1074\/jbc.RA119.010176_bib39","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.cell.2013.10.041","article-title":"Senescence is a developmental mechanism that contributes to embryonic growth and patterning","volume":"155","author":"Storer","year":"2013","journal-title":"Cell"},{"key":"10.1074\/jbc.RA119.010176_bib40","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.devcel.2014.11.012","article-title":"An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA","volume":"31","author":"Demaria","year":"2014","journal-title":"Dev. Cell"},{"key":"10.1074\/jbc.RA119.010176_bib41","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/nm.4000","article-title":"Cellular senescence in aging and age-related disease: from mechanisms to therapy","volume":"21","author":"Childs","year":"2015","journal-title":"Nat. Med"},{"key":"10.1074\/jbc.RA119.010176_bib42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ebiom.2017.04.013","article-title":"Cellular senescence: a translational perspective","volume":"21","author":"Kirkland","year":"2017","journal-title":"EBioMedicine"},{"key":"10.1074\/jbc.RA119.010176_bib43","doi-asserted-by":"crossref","first-page":"e12997","DOI":"10.7554\/eLife.12997","article-title":"Targeting senescent cells enhances adipogenesis and metabolic function in old age","volume":"4","author":"Xu","year":"2015","journal-title":"Elife"},{"key":"10.1074\/jbc.RA119.010176_bib44","doi-asserted-by":"crossref","first-page":"10954","DOI":"10.1128\/MCB.24.24.10954-10964.2004","article-title":"Ras\/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP\/p300 recruitment","volume":"24","author":"Foulds","year":"2004","journal-title":"Mol. Cell. Biol"},{"key":"10.1074\/jbc.RA119.010176_bib45","doi-asserted-by":"crossref","first-page":"e1000778","DOI":"10.1371\/journal.pgen.1000778","article-title":"DNA specificity determinants associate with distinct transcription factor functions","volume":"5","author":"Hollenhorst","year":"2009","journal-title":"PLoS Genet"},{"key":"10.1074\/jbc.RA119.010176_bib46","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/BF02621273","article-title":"Immuno-isolation and culture of biliary epithelial cells from normal human liver","volume":"25","author":"Joplin","year":"1989","journal-title":"In Vitro Cell Dev. Biol"},{"key":"10.1074\/jbc.RA119.010176_bib47","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1038\/nprot.2009.191","article-title":"Protocols to detect senescence-associated \u03b2-galactosidase (SA-\u03b2gal) activity, a biomarker of senescent cells in culture and in vivo","volume":"4","author":"Debacq-Chainiaux","year":"2009","journal-title":"Nat. Protoc"},{"key":"10.1074\/jbc.RA119.010176_bib48","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies senescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.RA119.010176_bib49","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1083\/jcb.144.5.903","article-title":"Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis","volume":"144","author":"Griffiths","year":"1999","journal-title":"J. Cell Biol"},{"key":"10.1074\/jbc.RA119.010176_bib50","doi-asserted-by":"crossref","first-page":"10777","DOI":"10.1074\/jbc.273.17.10777","article-title":"Bax in murine thymus is a soluble monomeric protein that displays differential detergent-induced conformations","volume":"273","author":"Hsu","year":"1998","journal-title":"J. Biol. Chem"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820304221?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820304221?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1074\/jbc.RA119.010176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:48:22Z","timestamp":1639702102000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925820304221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":50,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["S0021925820304221"],"URL":"https:\/\/doi.org\/10.1074\/jbc.ra119.010176","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The transcription factor ETS1 promotes apoptosis resistance of senescent cholangiocytes by epigenetically up-regulating the apoptosis suppressor BCL2L1","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1074\/jbc.RA119.010176","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 O'Hara et al.","name":"copyright","label":"Copyright"}]}}