title: Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP.
abstract: 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.
authors.affiliation: Department of Biology, McGill University, Montréal, Québec, Canada.
authors.forename: Gritta
authors.initials: G
authors.lastname: Tettweiler
authors.forename: Mathieu
authors.initials: M
authors.lastname: Miron
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkins
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lasko
mesh_terms: 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*
chemical_list: D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; C105238:cup protein, Drosophila