Reference Report

Reference
Citation	Nielsen, M.D., Luo, X., Biteau, B., Syverson, K., Jasper, H. (2008). 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell 7(5): 688--699. (Export to RIS)
FlyBase ID	FBrf0207166
Publication Type	Research paper
PubMed ID	18665908
PubMed Abstract	Antagonism between growth-promoting and stress-responsive signaling influences tissue homeostasis and longevity in metazoans. The transcription factor FoxO is central to this regulation, affecting cell proliferation, stress responses, apoptosis, and longevity. Insulin/IGF signaling promotes FoxO phosphorylation, causing its interaction with 14-3-3 molecules. The consequences of this interaction for FoxO-induced biological processes and for the regulation of lifespan in higher organisms remain unclear. Significant complexities in the effects of 14-3-3 proteins on lifespan have been uncovered in Caenorhabditis elegans, suggesting both positive and negative roles for 14-3-3 proteins in the control of aging. Using genetic and biochemical studies, we show here that 14-3-3epsilon antagonizes FoxO function in Drosophila. We find that dFoxO and 14-3-3epsilon proteins interact in vivo and that this interaction is lost in response to oxidative stress. Loss of 14-3-3epsilon results in increased stress-induced apoptosis, growth repression and extended lifespan of flies, phenotypes associated with elevated FoxO function. Our results further show that increased expression of 14-3-3epsilon reverts FoxO-induced growth defects. 14-3-3epsilon thus serves as a central modulator of FoxO activity in the regulation of growth, cell death and longevity in vivo.
DOI	10.1111/j.1474-9726.2008.00420.x
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Aging Cell
Title	Aging Cell
Publication Year	2002-
ISBN/ISSN	1474-9718 1474-9728
Data from Reference
Alleles (13)
	14-3-3ε^EP3578 14-3-3ε^ex4 14-3-3ε^j2B10 14-3-3ε^Scer\UAS.cCa foxo²¹ foxo^{Scer\UAS.T:Zzzz\FLAG} Scer\GAL4^arm.PS Scer\GAL4^{bun-Switch1.32} Scer\GAL4^GMR.PF Scer\GAL4^Ilp2.PR Scer\GAL4^ppl.PP Scer\GAL4^Switch1.106 Scer\GAL4^{αTub84B.Switch.PK}
Constructs (7)
	P{GAL4-arm.S} P{GAL4-ninaE.GMR} P{Ilp2-GAL4.R} P{ppl-GAL4.P} P{UAS-14-3-3ε.C} P{UAS-foxo.FLAG} P{αTub84B-Switch.K}
Genes (6)
	14-3-3ε 14-3-3ζ foxo Ilp2 Scer\GAL4 T:Zzzz\FLAG
Insertions (3)
	P{EP}14-3-3ε^EP3578 P{Switch1}106 P{Switch1}bun^Switch1.32