{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:11:29Z","timestamp":1787008289758,"version":"build-2736575974"},"reference-count":57,"publisher":"American Society for Cell Biology (ASCB)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:p>Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor \u03b2 (TGF-\u03b2)\/Smad signaling and is implicated in a wide variety of cellular responses, but the exact mechanisms that control Smurf2 abundance are largely unknown. Here we identify microRNA-322 (miR-322) and miR-503 as novel factors that regulate Smurf2 expression posttranscriptionally. Both miR-322 and miR-503 interact with Smurf2 mRNA via its 3\u2032-untranslated region (UTR) and repress Smurf2 translation but do not affect total Smurf2 mRNA levels. Studies using heterologous reporter constructs reveal a greater repressive effect of miR-322\/503 through a single binding site in the Smurf2 3\u2032-UTR, whereas point mutation of this site prevents miR-322\/503\u2013induced repression of Smurf2 translation. Increased levels of endogenous Smurf2 via antagonism of miR-322\/503 inhibits TGF-\u03b2\u2013induced Smad2 activation by increasing degradation of phosphorylated Smad2. Furthermore, the increase in Smurf2 in intestinal epithelial cells (IECs) expressing lower levels of miR-322\/503 is associated with increased resistance to apoptosis, which is abolished by Smurf2 silencing. These findings indicate that miR-322\/503 represses Smurf2 translation, in turn affecting intestinal epithelial homeostasis by altering TGF-\u03b2\/Smad2 signaling and IEC apoptosis.<\/jats:p>","DOI":"10.1091\/mbc.e13-09-0560","type":"journal-article","created":{"date-parts":[[2014,2,20]],"date-time":"2014-02-20T00:20:47Z","timestamp":1392855647000},"page":"1234-1243","source":"Crossref","is-referenced-by-count":65,"title":["Inhibition of Smurf2 translation by miR-322\/503 modulates TGF-\u03b2\/Smad2 signaling and intestinal epithelial homeostasis"],"prefix":"10.1091","volume":"25","author":[{"given":"Shan","family":"Cao","sequence":"first","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaladanki N.","family":"Rao","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Zou","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Liu","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dee","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Turner","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Gorospe","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, National Institute on Aging\u2013Intramural Research Program, National Institutes of Health, Baltimore, MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1053\/j.gastro.2011.07.038","volume":"141","author":"Bakirtzi K","year":"2011","journal-title":"Gastroenterology"},{"key":"B2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nm.2596","volume":"18","author":"Blank M","year":"2012","journal-title":"Nat Med"},{"key":"B3","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.molcel.2009.11.020","volume":"36","author":"Buchan JR","year":"2009","journal-title":"Mol Cell"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-05-0456"},{"key":"B4","first-page":"119","volume":"1835","author":"David D","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"B6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cell.2007.12.024","volume":"132","author":"Eulalio A","year":"2008","journal-title":"Cell"},{"key":"B7","doi-asserted-by":"crossref","first-page":"14264","DOI":"10.1074\/jbc.M112.432104","volume":"288","author":"Gamez B","year":"2013","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.molcel.2009.09.043","volume":"36","author":"Gao S","year":"2009","journal-title":"Mol Cell"},{"key":"B9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2104","volume":"8","author":"Garneau NL","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B10","doi-asserted-by":"crossref","first-page":"D140","DOI":"10.1093\/nar\/gkj112","volume":"34","author":"Griffiths-Jones S","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"B11","doi-asserted-by":"crossref","first-page":"671","DOI":"10.2307\/2527770","author":"Harter JL","year":"1960","journal-title":"Biometric"},{"key":"B12","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev.biochem.67.1.425","volume":"67","author":"Hershko A","year":"1998","journal-title":"Annu Rev Biochem"},{"key":"B13","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nrc1994","volume":"6","author":"Hoeller D","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"B14","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1038\/sj.onc.1207412","volume":"23","author":"Izzi L","year":"2004","journal-title":"Oncogene"},{"key":"B15","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1016\/j.cellsig.2013.06.001","volume":"25","author":"Kamato D","year":"2013","journal-title":"Cell Signal"},{"key":"B16","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.cell.2007.11.034","volume":"131","author":"Kedde M","year":"2007","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1042\/BST0380242","volume":"38","author":"Kulkarni M","year":"2010","journal-title":"Biochem Soc Trans"},{"key":"B18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.molcel.2010.09.027","volume":"40","author":"Leung AK","year":"2010","journal-title":"Mol Cell"},{"key":"B20","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1038\/sj.onc.1207319","volume":"23","author":"Li H","year":"2004","journal-title":"Oncogene"},{"key":"B21","doi-asserted-by":"crossref","first-page":"G992","DOI":"10.1152\/ajpgi.2001.280.5.G992","volume":"280","author":"Li L","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B19","doi-asserted-by":"crossref","first-page":"36818","DOI":"10.1074\/jbc.C000580200","volume":"275","author":"Lin X","year":"2000","journal-title":"J Biol Chem"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-07-0550"},{"key":"B23","doi-asserted-by":"crossref","first-page":"G1056","DOI":"10.1152\/ajpgi.00151.2003","volume":"285","author":"Liu L","year":"2003","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B24","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/70258","volume":"1","author":"Lo RS","year":"1999","journal-title":"Nat Cell Biol"},{"key":"B25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/cr.2008.308","volume":"19","author":"L\u00f6nn P","year":"2009","journal-title":"Cell Res"},{"key":"B26","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1101\/gad.1350705","volume":"19","author":"Massague J","year":"2005","journal-title":"Genes Dev"},{"key":"B27","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.cell.2012.02.005","volume":"148","author":"Mendell JT","year":"2012","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1093\/cvr\/cvt045","volume":"98","author":"Merlet E","year":"2013","journal-title":"Cardiovasc Res"},{"key":"B29","doi-asserted-by":"crossref","first-page":"22818","DOI":"10.1074\/jbc.M110.126920","volume":"285","author":"Nie J","year":"2010","journal-title":"J Biol Chem"},{"key":"B30","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1093\/nar\/gkp1100","volume":"38","author":"Nonne N","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"B31","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.molcel.2009.09.003","volume":"35","author":"Omer AD","year":"2009","journal-title":"Mol Cell"},{"key":"B32","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ymeth.2007.04.007","volume":"43","author":"Orom UA","year":"2007","journal-title":"Methods"},{"key":"B58","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1083\/jcb.80.2.248","volume":"80","author":"Quaroni A","year":"1979","journal-title":"J Cell Biol"},{"key":"B33","first-page":"11","volume-title":"Molecule to Function to Disease","author":"Rao JN","year":"2011"},{"key":"B34","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.molcel.2007.01.006","volume":"25","author":"Sapkota G","year":"2007","journal-title":"Mol Cell"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e10-01-0062"},{"key":"B36","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1234852","volume":"340","author":"Sato T","year":"2013","journal-title":"Science"},{"key":"B37","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/sj.emboj.7601580","volume":"26","author":"Schwamborn JC","year":"2007","journal-title":"EMBO J"},{"key":"B38","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1080\/10408360701250016","volume":"44","author":"Seiler N","year":"2007","journal-title":"Crit Rev Clin Lab Sci"},{"key":"B39","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","volume":"113","author":"Shi Y","year":"2003","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.tibs.2004.03.008","volume":"29","author":"Ten Dijke P","year":"2004","journal-title":"Trends Biochem Sci"},{"key":"B40","doi-asserted-by":"crossref","first-page":"G504","DOI":"10.1152\/ajpgi.1991.261.3.G504","volume":"261","author":"Wang JY","year":"1991","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B42","doi-asserted-by":"crossref","first-page":"C1474","DOI":"10.1152\/ajpcell.1995.269.6.C1474","volume":"269","author":"Wang JY","year":"1995","journal-title":"Am J Physiol Cell Physiol"},{"key":"B41","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1042\/BJ20091459","volume":"426","author":"Wang PY","year":"2010","journal-title":"Biochem J"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-01-0069"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-05-0287"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-07-0675"},{"key":"B46","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/j.febslet.2012.05.010","volume":"586","author":"Xu P","year":"2012","journal-title":"FEBS Lett"},{"key":"B47","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1053\/j.gastro.2011.07.005","volume":"141","author":"Ye D","year":"2011","journal-title":"Gastroenterology"},{"key":"B48","first-page":"85","volume":"24","author":"Yu TX","year":"2012","journal-title":"Mol Biol Cell"},{"key":"B49","doi-asserted-by":"crossref","first-page":"8472","DOI":"10.1093\/nar\/gkr567","volume":"39","author":"Yu TX","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"B50","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1073\/pnas.98.3.974","volume":"98","author":"Zhang Y","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B52","doi-asserted-by":"crossref","first-page":"22539","DOI":"10.1074\/jbc.M314337200","volume":"279","author":"Zhang HM","year":"2004","journal-title":"J Biol Chem"},{"key":"B53","doi-asserted-by":"crossref","first-page":"7623","DOI":"10.1093\/nar\/gkp755","volume":"37","author":"Zhang X","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"B54","doi-asserted-by":"crossref","first-page":"7905","DOI":"10.1093\/nar\/gkt565","volume":"41","author":"Zhuang R","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B55","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/23293","volume":"400","author":"Zhu H","year":"1999","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"crossref","first-page":"5021","DOI":"10.1128\/MCB.00807-10","volume":"30","author":"Zou T","year":"2010","journal-title":"Mol Cell Biol"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2019,7,14]],"date-time":"2019-07-14T11:34:12Z","timestamp":1563104052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.e13-09-0560"}},"subtitle":[],"editor":[{"given":"Thomas M.","family":"Magin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,4,15]]},"references-count":57,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,4,15]]}},"alternative-id":["10.1091\/mbc.e13-09-0560"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e13-09-0560","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,15]]}}}