The Caenorhabditis elegans Oxidative Stress Response Requires the NHR-49 Transcription Factor
Authors
Hu, QueenieD'Amora, Dayana R.
MacNeil, Lesley T.
Walhout, Albertha J. M.
Kubiseski, Terrance J.
Document Type
Journal ArticlePublication Date
2018-12-10Keywords
C. elegansNHR-49
SKN-1
oxidative stress
reactive oxygen species
Amino Acids, Peptides, and Proteins
Biochemistry, Biophysics, and Structural Biology
Cellular and Molecular Physiology
Enzymes and Coenzymes
Genetic Phenomena
Genetics and Genomics
Systems Biology
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Show full item recordAbstract
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.Source
G3 (Bethesda). 2018 Dec 10;8(12):3857-3863. doi: 10.1534/g3.118.200727. Link to article on publisher's site
DOI
10.1534/g3.118.200727Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40853PubMed ID
30297383Related Resources
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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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1534/g3.118.200727
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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.