Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis
Selenium, 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 se...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2017
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| Online Access: | http://hdl.handle.net/1721.1/108671 |
| _version_ | 1810986815481446400 |
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| author | Cox, 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 Asara, John M. Houvras, Yariv Gladyshev, Vadim N. Goessling, Wolfram Chang, Christopher J., 1974- |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Cox, 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 Asara, John M. Houvras, Yariv Gladyshev, Vadim N. Goessling, Wolfram Chang, Christopher J., 1974- |
| author_sort | Cox, Andrew G. |
| collection | MIT |
| description | Selenium, 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. |
| first_indexed | 2024-09-23T11:40:13Z |
| format | Article |
| id | mit-1721.1/108671 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:40:13Z |
| publishDate | 2017 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1086712022-10-01T05:10:47Z Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis Cox, 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 Asara, John M. Houvras, Yariv Gladyshev, Vadim N. Goessling, Wolfram Chang, Christopher J., 1974- Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Goessling, Wolfram Selenium, 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. National Cancer Institute (U.S.) (Grant R01 DK090311) National Cancer Institute (U.S.) (Grant R24OD017870) 2017-05-04T18:12:05Z 2017-05-04T18:12:05Z 2016-09 2016-02 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/108671 Cox, 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 Sciences en_US http://dx.doi.org/10.1073/pnas.1600204113 Proceedings of the National Academy of Sciences Article 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. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Cox, 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 Asara, John M. Houvras, Yariv Gladyshev, Vadim N. Goessling, Wolfram Chang, Christopher J., 1974- Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis |
| title | Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis |
| title_full | Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis |
| title_fullStr | Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis |
| title_full_unstemmed | Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis |
| title_short | Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis |
| title_sort | selenoprotein h is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis |
| url | http://hdl.handle.net/1721.1/108671 |
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