UMMS Affiliation

Program in Systems Biology; Program in Molecular Medicine

Publication Date

2018-12-10

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Cellular and Molecular Physiology | Enzymes and Coenzymes | Genetic Phenomena | Genetics and Genomics | Systems Biology

Abstract

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.

Keywords

C. elegans, NHR-49, SKN-1, oxidative stress, reactive oxygen species

Rights and Permissions

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.

DOI of Published Version

10.1534/g3.118.200727

Source

G3 (Bethesda). 2018 Dec 10;8(12):3857-3863. doi: 10.1534/g3.118.200727. Link to article on publisher's site

Journal/Book/Conference Title

G3 (Bethesda, Md.)

Related Resources

Link to Article in PubMed

PubMed ID

30297383

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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