Reference Report

Reference
Citation	Junger, M.A., Rintelen, F., Stocker, H., Wasserman, J.D., Vegh, M., Radimerski, T., Greenberg, M.E., Hafen, E. (2003). The Drosophila Forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J. Biol. 2(3): 20. (Export to RIS)
FlyBase ID	FBrf0162177
Publication Type	Research paper
External Crossreferences
PubMed ID	12908874
PubMed Abstract	Forkhead transcription factors belonging to the FOXO subfamily are negatively regulated by protein kinase B (PKB) in response to signaling by insulin and insulin-like growth factor in Caenorhabditis elegans and mammals. In Drosophila, the insulin-signaling pathway regulates the size of cells, organs, and the entire body in response to nutrient availability, by controlling both cell size and cell number. In this study, we present a genetic characterization of dFOXO, the only Drosophila FOXO ortholog.Ectopic expression of dFOXO and human FOXO3a induced organ-size reduction and cell death in a manner dependent on phosphoinositide (PI) 3-kinase and nutrient levels. Surprisingly, flies homozygous for dFOXO null alleles are viable and of normal size. They are, however, more sensitive to oxidative stress. Furthermore, dFOXO function is required for growth inhibition associated with reduced insulin signaling. Loss of dFOXO suppresses the reduction in cell number but not the cell-size reduction elicited by mutations in the insulin-signaling pathway. By microarray analysis and subsequent genetic validation, we have identified d4E-BP, which encodes a translation inhibitor, as a relevant dFOXO target gene.Our results show that dFOXO is a crucial mediator of insulin signaling in Drosophila, mediating the reduction in cell number in insulin-signaling mutants. We propose that in response to cellular stresses, such as nutrient deprivation or increased levels of reactive oxygen species, dFOXO is activated and inhibits growth through the action of target genes such as d4E-BP.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Biol.
Title	Journal of Biology
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Publication Year	2002-
ISBN/ISSN	1475-4924
Data from Reference
Alleles (21)
	Akt1¹ Akt1³ chico¹ chico^flp147E foxo²¹ foxo²⁵ foxo^EP35-147 foxo^Scer\UAS.cFa foxo^TM.Scer\UAS Hsap\FOXO3A^Scer\UAS.cFa Hsap\FOXO3A^TM.Scer\UAS InR³⁰⁴ Pi3K92E^5W3 Pi3K92E^{D954A.Scer\UAS.T:Hsap\MYC} Pten¹¹⁷ Scer\GAL4^GMR.PB Scer\GAL4^GMR.PF Scer\GAL4^Scer\FRT.GMR Thor^k13517 Tsc1^Q87X w^+mC
Constructs (8)
	P{Dp110^D954A} P{GAL4-ninaE.GMR} P{GMR-GAL4.FRT} P{GMR-GAL4(FRT-)} P{UAS-foxo.F} P{UAS-foxo.TM} P{UAS-hFOXO3a.F} P{UAS-hFOXO3a-TM}
Genes (23)
	Akt1 Cdk8 cenG1A CG9009 chico Cyp4e2 Cyp9c1 DNApol-ι egr Exn foxo Hsap\FOXO3A InR Pepck PhKγ Pi3K92E Pten Scer\GAL4 T:Hsap\MYC Thor Tsc1 w whd
Insertions (1)
	P{EP}foxo^EP35-147