SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response.

By J. An, T. Blackwell. Genes & Development, 2003

737 citations recorded by the source corpus.

During the earliest stages of Caenorhabditis elegans embryogenesis, the transcription factor SKN-1 initiates development of the digestive system and other mesendodermal tissues. Postembryonic SKN-1 functions have not been elucidated. SKN-1 binds to DNA through a unique mechanism, but is distantly related to basic leucine-zipper proteins that orchestrate the major oxidative stress response in vertebrates and yeast. Here we show that despite its distinct mode of target gene recognition, SKN-1 functions similarly to resist oxidative stress in C. elegans. During postembryonic stages, SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively. SKN-1 is present in ASI nuclei under normal conditions, and accumulates in intestinal nuclei in response to oxidative stress. skn-1 mutants are sensitive to oxidative stress and have shortened lifespans. SKN-1 represents a connection between developmental specification of the digestive system and one of its most basic functions, resistance to oxidative and xenobiotic stress. This oxidative stress response thus appears to be both widely conserved and ancient, suggesting that the mesendodermal specification role of SKN-1 was predated by its function in these detoxification mechanisms.

Subfields: Aging, Endocrine and Autonomic Systems, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8f8c524ad5b39187dfc01016927a505d782bdf7e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

In Endocrine and Autonomic Systems

In Molecular Biology

Citations in the corpus

Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. (2008, positive): “Each of two skn-1 alleles that we analyzed (zu67 and zu129) completely eliminated Cell 132, 1025–1038, March 21, 2008 Schematics of the gcs-1 promoter (An and Blackwell, 2003) and the GST-7::GFP translational fusion.”
A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. (2006, positive): “elegans Life-Span Analysis Life-span experiments were carried out as described (An and Blackwell, 2003).”
The cytoprotective role of the Keap1–Nrf2 pathway (2011, background): “Nrf2 is conserved in bilaterans with homologues found in nematodes, flies, fish and mammals and was identified due to its ability to bind to NF-E2/AP-1 enhancer elements in cDNA library screens (Moi et al. 1994; Itoh et al. 1995; Kobayashi et al. 2002; An and Blackwell 2003; Sykiotis and Bohmann 200”
Role of nrf2 in oxidative stress and toxicity. (2013, background): “In invertebrates, Caenorhabditis elegans protein skinhead-1 (SKN-1) has significant homology with Nrf2 and binds to an ARE-like element to regulate oxidative stress–related genes (80).”
Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism (2016, background): “In the nucleus, it binds to DNA (to the consensus WWTRTCAT (W = A/T, R = G/A) sequence) as a monomer through a basic region (BR) [18].”
Stress-Activated Cap’n’collar Transcription Factors in Aging and Human Disease (2010, neutral): “drogen peroxide, paraquat, arsenic, and juglone (147, 148).”
TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO (2012, background): “Expression or nuclear accumulation of transgenic GFP proteins was scored as ''low,'' ''medium,'' or ''high'' essentially as published (An and Blackwell, 2003 ; Figure 7.”
Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. (2008, background): “SKN-1 is apparently regulated mainly by phosphorylation, and binds DNA as a monomer (An and Blackwell, 2003; Blackwell et al., 1994; Inoue et al., 2005).”