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dc.contributor.authorCox, Andrew G.
dc.contributor.authorTsomides, Allison
dc.contributor.authorKim, Andrew J.
dc.contributor.authorSaunders, Diane
dc.contributor.authorHwang, Katie L.
dc.contributor.authorEvason, Kimberley J.
dc.contributor.authorHeidel, Jerry
dc.contributor.authorBrown, Kristin K.
dc.contributor.authorYuan, Min
dc.contributor.authorLien, Evan C.
dc.contributor.authorLee, Byung Cheon
dc.contributor.authorNissim, Sahar
dc.contributor.authorDickinson, Bryan
dc.contributor.authorChhangawala, Sagar
dc.contributor.authorChang, Christopher J.
dc.contributor.authorAsara, John M.
dc.contributor.authorHouvras, Yariv
dc.contributor.authorGladyshev, Vadim N.
dc.contributor.authorGoessling, Wolfram
dc.date.accessioned2017-05-04T18:12:05Z
dc.date.available2017-05-04T18:12:05Z
dc.date.issued2016-09
dc.date.submitted2016-02
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/108671
dc.description.abstractSelenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LC-MS/MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels.en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant R01 DK090311)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant R24OD017870)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1600204113en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleSelenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesisen_US
dc.typeArticleen_US
dc.identifier.citationCox, Andrew G. et al. “Selenoprotein H Is an Essential Regulator of Redox Homeostasis That Cooperates with p53 in Development and Tumorigenesis.” Proceedings of the National Academy of Sciences 113.38 (2016): E5562–E5571. © 2017 National Academy of Sciencesen_US
dc.contributor.departmentInstitute for Medical Engineering and Scienceen_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.mitauthorGoessling, Wolfram
dc.relation.journalProceedings of the National Academy of Sciencesen_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.orderedauthorsCox, Andrew G.; Tsomides, Allison; Kim, Andrew J.; Saunders, Diane; Hwang, Katie L.; Evason, Kimberley J.; Heidel, Jerry; Brown, Kristin K.; Yuan, Min; Lien, Evan C.; Lee, Byung Cheon; Nissim, Sahar; Dickinson, Bryan; Chhangawala, Sagar; Chang, Christopher J.; Asara, John M.; Houvras, Yariv; Gladyshev, Vadim N.; Goessling, Wolframen_US
dspace.embargo.termsNen_US
mit.licensePUBLISHER_POLICYen_US


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