RRC ID |
45556
|
著者 |
Dresen A, Finkbeiner S, Dottermusch M, Beume JS, Li Y, Walz G, Neumann-Haefelin E.
|
タイトル |
Caenorhabditis elegans OSM-11 signaling regulates SKN-1/Nrf during embryonic development and adult longevity and stress response.
|
ジャーナル |
Dev Biol
|
Abstract |
The Nrf family of transcription factors is critical for stress defense and detoxification. In Caenorhabditis elegans, the Nrf protein ortholog SKN-1 mediates this conserved stress response and promotes longevity. Moreover, SKN-1 is well known for its essential functions during C. elegans embryogenesis. SKN-1 is maternally deployed and initiates a signaling network specifying development of the endoderm and mesoderm. In this study, we identify the conserved Notch ligand OSM-11 as a novel regulator of SKN-1. We find that genetic inactivation of osm-11 re-establishes development of the pharynx and intestine in skn-1 deficient embryos and thereby rescues embryonic lethality associated with loss of skn-1 function. Inactivation of other DSL- and DOS-motif Notch ligands does not prevent skn-1 embryonic lethality. In addition, we show that inactivation of osm-11 in adult worms robustly enhances lifespan and promotes resistance to environmental stress. SKN-1 is required for increased longevity and heat and oxidative stress resistance but not hyperosmotic stress conferred by osm-11. OSM-11 prevents the nuclear accumulation of SKN-1 and represses the transcriptional activation of SKN-1 target genes for cellular detoxification. Our findings indicate that OSM-11 antagonizes SKN-1 during embryonic development and reveal a highly context-specific relationship between OSM-11 and SKN-1 in promoting stress resistance and longevity.
|
巻・号 |
400(1)
|
ページ |
118-31
|
公開日 |
2015-4-1
|
DOI |
10.1016/j.ydbio.2015.01.021
|
PII |
S0012-1606(15)00041-X
|
PMID |
25637691
|
MeSH |
Aging / metabolism
Animals
Animals, Genetically Modified
Caenorhabditis elegans / embryology*
Caenorhabditis elegans / growth & development
Caenorhabditis elegans Proteins / metabolism*
DNA-Binding Proteins / metabolism*
Gene Expression Regulation, Developmental / physiology*
Intracellular Signaling Peptides and Proteins / metabolism*
Longevity / genetics
Longevity / physiology*
Oxidative Stress / physiology
RNA Interference
Signal Transduction / physiology*
Transcription Factors / metabolism*
|
IF |
2.896
|
引用数 |
7
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
|
リソース情報 |
線虫 |
tm3411
tm2256 |