Reference Report

Reference
Citation	Sykiotis, G.P., Bohmann, D. (2008). Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev. Cell 14(1): 76--85. (Export to RIS)
FlyBase ID	FBrf0202699
Publication Type	Research paper
PubMed ID	18194654
PubMed Abstract	Keap1/Nrf2 signaling defends organisms against the detrimental effects of oxidative stress and has been suggested to abate its consequences, including aging-associated diseases like neurodegeneration, chronic inflammation, and cancer. Nrf2 is a prominent target for drug discovery, and Nrf2-activating agents are in clinical trials for cancer chemoprevention. However, aberrant activation of Nrf2 by keap1 somatic mutations may contribute to carcinogenesis and promote resistance to chemotherapy. To evaluate potential functions of Keap1 and Nrf2 for organismal homeostasis, we characterized the pathway in Drosophila. We demonstrate that Keap1/Nrf2 signaling in the fruit fly is activated by oxidants, induces antioxidant and detoxification responses, and confers increased tolerance to oxidative stress. Importantly, keap1 loss-of-function mutations extend the lifespan of Drosophila males, supporting a role for Nrf2 signaling in the regulation of longevity. Interestingly, cancer chemopreventive drugs potently stimulate Drosophila Nrf2 activity, suggesting the fruit fly as an experimental system to identify and characterize such agents.
DOI	10.1016/j.devcel.2007.12.002
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Dev. Cell
Title	Developmental Cell
Publication Year	2001-
ISBN/ISSN
Data from Reference
Alleles (17)
	Avic\GFP^GstD1.PS Avic\GFP^GstD1.ΔARE cnc^{dsRNA.Scer\UAS} cnc^Scer\UAS.cSa cnc^Scer\UAS.cVa Ecol\lacZ^4C Ecol\lacZ^GstD1.PS Keap1⁰³⁶ Keap1^{dsRNA.Scer\UAS} Keap1^EY1 Keap1^EY5 Keap1^EY02632 Keap1^Scer\UAS.cSa Scer\GAL4^en-e16E Scer\GAL4^GMR.PF Scer\GAL4^sev.EP Scer\GAL4^{αTub84B.Switch.PK}
Constructs (12)
	P{CBS-lacZ.4C} P{GAL4-ninaE.GMR} P{GstD1-GFP.S} P{GstD1-GFP.ΔARE} P{GstD1-lacZ.S} P{sevEP-GAL4.B} P{UAS-cnc.B} P{UAS-cnc.C.RNAi} P{UAS-cnc.C} P{UAS-Keap1.RNAi} P{UAS-Keap1.S} P{αTub84B-Switch.K}
Genes (6)
	Avic\GFP cnc Ecol\lacZ GstD1 Keap1 Scer\GAL4
Insertions (4)
	P{en2.4-GAL4}e16E P{EPgy2}Keap1^EY02632 P{αTub84B-Switch.K}5 P{αTub84B-Switch.K}10
Natural transposons (1)
	P-element