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Dev Biol. 2015 Apr 1;400(1):118-31. doi: 10.1016/j.ydbio.2015.01.021. Epub 2015 Jan 29.

Caenorhabditis elegans OSM-11 signaling regulates SKN-1/Nrf during embryonic development and adult longevity and stress response.

Author information

1
Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany.
2
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.
3
Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany. Electronic address: elke.neumann-haefelin@uniklinik-freiburg.de.

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.

KEYWORDS:

Aging; C. elegans; Development; Notch signaling; OSM-11; SKN-1/Nrf; Stress response

PMID:
25637691
DOI:
10.1016/j.ydbio.2015.01.021
[Indexed for MEDLINE]
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