title: Caenorhabditis elegans OSM-11 signaling regulates SKN-1/Nrf during embryonic development and adult longevity and stress response.
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.
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors: Arne
authors: A
authors: Dresen
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors: Sandra
authors: S
authors: Finkbeiner
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors: Matthias
authors: M
authors: Dottermusch
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors: Jan-Sebastian
authors: JS
authors: Beume
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors: Yujie
authors: Y
authors: Li
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany; Center for Biological Signaling Studies (bioss), University of Freiburg, D-79104 Freiburg, Germany.
authors: Gerd
authors: G
authors: Walz
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany. Electronic address: elke.neumann-haefelin@uniklinik-freiburg.de.
authors: Elke
authors: E
authors: Neumann-Haefelin
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C532484:OSM-11 protein, C elegans; D014157:Transcription Factors; C073702:skn-1 protein, C elegans
keywords: Aging; C. elegans; Development; Notch signaling; OSM-11; SKN-1/Nrf; Stress response