Principal Investigator

Dirk Bohmann, Ph.D. University of Rochester work Box 633 601 Elmwood Ave Rochester NY 14642 office: KMRB 2-9639 p 585-273-1446

NRF2 Signaling

Flies that have been treated with oltipraz, a cancer chemoprevention drug that stimulates NRF2 respond with increased NRF2 activity as visualized here by a GFP reporter.

Nrf2 is a signal-activated transcription factor that had previously been characterized in mammals, where it mediates responses to electrophiles, oxidative stress and carcinogens. Nrf2-induced processes protect many organs, including the gastrointestinal tract and the nervous system, from xenobiotic damage. Importantly, Nrf2 is a prominent target for cancer chemo-preventive interventions and Nrf2-activating agents are currently being evaluated for therapeutic utility in clinical trials. We isolated mutants of Drosophila Nrf2 and of Keap1, its repressor, and showed that the pathway is functionally conserved in fruit flies. We find that Nrf2-activating drugs are functional in Drosophila and that elevated Nrf2 signaling can extend lifespan (Sykiotis and Bohmann, 2008). According to these studies Drosophila can serve as a system in which the pharmacology of the drug target Nrf2, and the function of Nrf2 signaling in the aging process can be explored.

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