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