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dc.contributor.authorGraham, Daniel B.
dc.contributor.authorLefkovith, Ariel
dc.contributor.authorDeelen, Patrick
dc.contributor.authorde Klein, Niek
dc.contributor.authorBoroughs, Angela
dc.contributor.authorDesch, A. Nicole
dc.contributor.authorNg, Aylwin C.Y.
dc.contributor.authorPetersen, Christine P.
dc.contributor.authorBhan, Atul K.
dc.contributor.authorWijmenga, Cisca
dc.contributor.authorVarma, Mukund Madhav
dc.contributor.authorGuzman, Gaelen Donnelly
dc.contributor.authorSchenone, Monica
dc.contributor.authorRivas, Manuel A
dc.contributor.authorDaly, Mark J
dc.contributor.authorCarr, Steven A
dc.contributor.authorXavier, Ramnik Joseph
dc.date.accessioned2017-04-03T14:32:23Z
dc.date.available2017-04-03T14:32:23Z
dc.date.issued2016-12
dc.date.submitted2016-09
dc.identifier.issn22111247
dc.identifier.urihttp://hdl.handle.net/1721.1/107818
dc.description.abstractSummary - Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5–61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis.en_US
dc.description.sponsorshipLeona M. and Harry B. Helmsley Charitable Trust (2014PG-IBD016)en_US
dc.description.sponsorshipCrohn's and Colitis Foundation of Americaen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant DK043351)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant DK097485)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.celrep.2016.11.042en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceElsevieren_US
dc.titleTMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammationen_US
dc.typeArticleen_US
dc.identifier.citationGraham, Daniel B., Ariel Lefkovith, Patrick Deelen, Niek de Klein, Mukund Varma, Angela Boroughs, A. Nicole Desch, et al. “TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation.” Cell Reports 17, no. 11 (December 2016): 2955–2965.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.mitauthorVarma, Mukund Madhav
dc.contributor.mitauthorGuzman, Gaelen Donnelly
dc.contributor.mitauthorSchenone, Monica
dc.contributor.mitauthorRivas, Manuel A
dc.contributor.mitauthorDaly, Mark J
dc.contributor.mitauthorCarr, Steven A
dc.contributor.mitauthorXavier, Ramnik Joseph
dc.relation.journalCell Reportsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsGraham, Daniel B.; Lefkovith, Ariel; Deelen, Patrick; de Klein, Niek; Varma, Mukund; Boroughs, Angela; Desch, A. Nicole; Ng, Aylwin C.Y.; Guzman, Gaelen; Schenone, Monica; Petersen, Christine P.; Bhan, Atul K.; Rivas, Manuel A.; Daly, Mark J.; Carr, Steven A.; Wijmenga, Cisca; Xavier, Ramnik J.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-8261-8346
dc.identifier.orcidhttps://orcid.org/0000-0002-7203-4299
mit.licensePUBLISHER_CCen_US


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