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Molecular and Cellular Biology, October 2009, p. 5357-5365, Vol. 29, No. 19
0270-7306/09/$08.00+0     doi:10.1128/MCB.00302-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Drosophila FoxO Regulates Organism Size and Stress Resistance through an Adenylate Cyclase{triangledown} ,{dagger}

Jaakko Mattila,1 Anna Bremer,1,{ddagger} Linda Ahonen,2 Risto Kostiainen,2 and Oscar Puig1*

Institute of Biotechnology, University of Helsinki, Viikinkaari 9, 00014 Helsinki, Finland,1 Faculty of Pharmacy, Division of Pharmaceutical Chemistry, University of Helsinki, Viikinkaari 9, 00014 Helsinki, Finland2

Received 8 March 2009/ Returned for modification 27 April 2009/ Accepted 20 July 2009

Forkhead box class O (FoxO) transcription factors are a family of conserved proteins that regulate the cellular responses to various stimuli, such as energy deprivation, stress, and developmental cues. FoxO proteins are important mediators of the insulin signaling pathway, adjusting growth and metabolism to nutrient availability. Insulin signaling acts together with the glucagon-stimulated cAMP signaling pathway to orchestrate the organism response to various nutritional conditions. In this study, we demonstrate that Drosophila melanogaster FoxO (dFoxO) regulates cAMP signaling by directly inducing the expression of an adenylate cyclase gene, ac76e. Interestingly, ac76e is expressed in a highly restricted pattern throughout fly development, limited to the corpus allatum (CA), gastric cecum, and malpighian tubules. dFoxO activation of AC76E in the CA increases starvation resistance and limits growth. Our results unravel a new role for dFoxO, integrating cAMP and insulin signaling to adapt organism growth to the existing nutritional conditions.

* Corresponding author. Present address: Department of Molecular Profiling, Merck Research Laboratories, 126 East Lincoln Ave., RY80M-179, Rahway, NJ 07065. Phone: (732) 594 6758. Fax: (732) 594 2929. E-mail: oscar_puig{at}merck.com

{triangledown} Published ahead of print on 3 August 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstr. 11, 07745 Jena, Germany.

Molecular and Cellular Biology, October 2009, p. 5357-5365, Vol. 29, No. 19
0270-7306/09/$08.00+0     doi:10.1128/MCB.00302-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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