| RRC ID |
59356
|
| 著者 |
Hu Q, D'Amora DR, MacNeil LT, Walhout AJM, Kubiseski TJ.
|
| タイトル |
The Caenorhabditis elegans Oxidative Stress Response Requires the NHR-49 Transcription Factor.
|
| ジャーナル |
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.
|
| 巻・号 |
8(12)
|
| ページ |
3857-3863
|
| 公開日 |
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
|
| 引用数 |
7
|
| リソース情報 |
| 線虫 |
tm2182
tm1817 |
