14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila.

Authors: Nielsen, Mette Damgaard; Luo, Xi; Biteau, Benoit; Syverson, Keith; Jasper, Heinrich

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.

Keywords: 14-3-3 Proteins/*physiology; Animals; Animals, Genetically Modified; Apoptosis/genetics/*physiology; Drosophila Proteins/*antagonists & inhibitors/physiology; Drosophila melanogaster/*cytology/genetics/*growth & development; Female; Forkhead Transcription Factors/*antagonists & inhibitors/physiology; Longevity/genetics/*physiology; Male; Oxidative Stress/genetics; Protein Isoforms/metabolism/physiology; Retina/growth & development/metabolism; Sequence Homology, Amino Acid; Signal Transduction/genetics/physiology
Journal: Aging Cell
Volume: 7
Issue: 5
Pages: 688-99
Date: Oct. 1, 2008
PMID: 18665908
Select reference article to upload


Citation:

Nielsen, Mette Damgaard, Luo, Xi, Biteau, Benoit, Syverson, Keith, Jasper, Heinrich (2008) 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell 7: 688-99.


Study Lifespan Factors:
  • 14-3-3epsilon CG31196 gene product from transcript CG31196-RA


  • Update (Admin) | Auto-Update

    Comment on This Data Unit