Oliveira, Riva P. et al. (2009) International Worm Meeting "Condition-adapted stress and longevity gene regulation by C. elegans SKN-1/Nrf."

Ashraf, Jasmine, Murphy, Coleen T., Oliveira, Riva P., Porter Abate, Jess, Dilks, Kieran, Landis, Jessica, Blackwell, T. Keith

[International Worm Meeting, 2009]

In C. elegans the transcription regulator SKN-1 is important for oxidative stress resistance and acts in multiple longevity pathways, including insulin/IGF-1-like signaling (IIS). SKN-1 is the ortholog of mammalian Nrf proteins, which induce Phase 2 detoxification genes in response to stress. Here we have used expression profiling to identify genes and processes that are regulated by SKN-1 under normal and stress-response conditions. Under normal conditions SKN-1 upregulates numerous genes involved in detoxification and related functions. Surprisingly, SKN-1 also downregulates a set of genes that reduce stress resistance and lifespan, including the IIS genes ins-7 and pdk-1. In each case, many of these genes appear to be direct SKN-1 targets. The metalloid sodium arsenite induces skn-1-dependent activation of certain detoxification gene groups, some of which were not SKN-1-upregulated under normal conditions. Another stressor, an organic peroxide, also triggers induction of a discrete Phase 2 gene set, but additionally stimulates a broad SKN-1-independent response. We conclude that under normal conditions SKN-1 has a wide range of functions in detoxification and other processes, including modulating mechanisms that reduce stress resistance and lifespan. In response to stress, SKN-1 and other regulators tailor transcription programs to meet the challenge at hand. Our findings reveal striking complexity in SKN-1 functions and in the regulation of systemic detoxification defenses.