RRC ID 59356
Author Hu Q, D'Amora DR, MacNeil LT, Walhout AJM, Kubiseski TJ.
Title The Caenorhabditis elegans Oxidative Stress Response Requires the NHR-49 Transcription Factor.
Journal G3 (Bethesda)
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.
Volume 8(12)
Pages 3857-3863
Published 2018-12-10
DOI 10.1534/g3.118.200727
PII g3.118.200727
PMID 30297383
PMC PMC6288832
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Expression Regulation / physiology* Gene Knockdown Techniques Oxidative Stress / physiology* Reactive Oxygen Species / metabolism* Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Transcription Factors / genetics Transcription Factors / metabolism*
IF 2.63
Times Cited 7
C.elegans tm2182 tm1817