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dc.contributor.authorHu, Queenie
dc.contributor.authorD'Amora, Dayana R.
dc.contributor.authorMacNeil, Lesley T.
dc.contributor.authorWalhout, Albertha J. M.
dc.contributor.authorKubiseski, Terrance J.
dc.date2022-08-11T08:09:51.000
dc.date.accessioned2022-08-23T16:46:18Z
dc.date.available2022-08-23T16:46:18Z
dc.date.issued2018-12-10
dc.date.submitted2018-12-12
dc.identifier.citation<p>G3 (Bethesda). 2018 Dec 10;8(12):3857-3863. doi: 10.1534/g3.118.200727. <a href="https://doi.org/10.1534/g3.118.200727">Link to article on publisher's site</a></p>
dc.identifier.issn2160-1836 (Linking)
dc.identifier.doi10.1534/g3.118.200727
dc.identifier.pmid30297383
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40853
dc.description.abstractThe overproduction of reactive oxygen species (ROS) in cells can lead to the development of diseases associated with aging. We have previously shown that C. elegans BRAP-2 (Brca1 associated binding protein 2) regulates phase II detoxification genes such as gst-4, by increasing SKN-1 activity. Previously, a transcription factor (TF) RNAi screen was conducted to identify potential activators that are required to induce gst-4 expression in brap-2(ok1492) mutants. The lipid metabolism regulator NHR-49/HNF4 was among 18 TFs identified. Here, we show that knockdown of nhr-49 suppresses the activation of gst-4 caused by brap-2 inactivation and that gain-of-function alleles of nhr-49 promote gst-4 expression. We also demonstrate that nhr-49 and its cofactor mdt-15 are required to express phase II detoxification enzymes upon exposure to chemicals that induce oxidative stress. Furthermore, we show that NHR-49 and MDT-15 enhance expression of skn-1a/c These findings identify a novel role for NHR-49 in ROS detoxification by regulating expression of SKN-1C and phase II detoxification genes.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30297383&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2018 Hu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectC. elegans
dc.subjectNHR-49
dc.subjectSKN-1
dc.subjectoxidative stress
dc.subjectreactive oxygen species
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectCellular and Molecular Physiology
dc.subjectEnzymes and Coenzymes
dc.subjectGenetic Phenomena
dc.subjectGenetics and Genomics
dc.subjectSystems Biology
dc.titleThe Caenorhabditis elegans Oxidative Stress Response Requires the NHR-49 Transcription Factor
dc.typeJournal Article
dc.source.journaltitleG3 (Bethesda, Md.)
dc.source.volume8
dc.source.issue12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4671&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3659
dc.identifier.contextkey13473124
refterms.dateFOA2022-08-23T16:46:18Z
html.description.abstract<p>The overproduction of reactive oxygen species (ROS) in cells can lead to the development of diseases associated with aging. We have previously shown that C. elegans BRAP-2 (Brca1 associated binding protein 2) regulates phase II detoxification genes such as gst-4, by increasing SKN-1 activity. Previously, a transcription factor (TF) RNAi screen was conducted to identify potential activators that are required to induce gst-4 expression in brap-2(ok1492) mutants. The lipid metabolism regulator NHR-49/HNF4 was among 18 TFs identified. Here, we show that knockdown of nhr-49 suppresses the activation of gst-4 caused by brap-2 inactivation and that gain-of-function alleles of nhr-49 promote gst-4 expression. We also demonstrate that nhr-49 and its cofactor mdt-15 are required to express phase II detoxification enzymes upon exposure to chemicals that induce oxidative stress. Furthermore, we show that NHR-49 and MDT-15 enhance expression of skn-1a/c These findings identify a novel role for NHR-49 in ROS detoxification by regulating expression of SKN-1C and phase II detoxification genes.</p>
dc.identifier.submissionpathoapubs/3659
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentProgram in Systems Biology
dc.source.pages3857-3863


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Copyright © 2018 Hu et al.  This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright © 2018 Hu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.