Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP.
eIF4E, the mRNA 5' cap-binding protein, is regulated by its binding protein (4E-BP), a downstream target of phosphatidylinositol-3-OH kinase [PI(3)K] signaling. We show that Drosophila 4E-BP (d4E-BP) activity becomes critical for survival under dietary restriction and oxidative stress, and is linked to life span. The Drosophila forkhead transcription factor (dFOXO) activates d4E-BP transcription. We show that ectopic expression of d4E-BP in dFOXO-null flies restores oxidative stress resistance to control levels. Thus, d4E-BP is an important downstream effector of a dFOXO phenotype, and regulation of translation by eIF4E is vital during environmental stress.
Tettweiler
Gritta
G
Department of Biology, McGill University, Montréal, Québec, Canada.
Miron
Mathieu
M
Jenkins
Mark
M
Sonenberg
Nahum
N
Lasko
Paul F
PF
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D008136:Longevity / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D013217:Starvation / Q000378:metabolism*
D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; C105238:cup protein, Drosophila