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Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP

  1. Gritta Tettweiler1,2,
  2. Mathieu Miron2,3,
  3. Mark Jenkins1,
  4. Nahum Sonenberg2, and
  5. Paul F. Lasko1,4
  1. 1Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada; 2Department of Biochemistry and McGill Cancer Center, McGill University, Montréal, Québec H3G 1Y6, Canada

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.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1311805.

  • ↵3 Present address: McGill University and Genome Québec Innovation Centre, 740 Avenue Dr. Penfield, Montréal, Québec H3A 1A4, Canada.

  • ↵4 Corresponding author.

    ↵4 E-MAIL paul.lasko@mcgill.ca; FAX (514) 398-5069.

    • Accepted June 13, 2005.
    • Received March 2, 2005.
  1. Published in Advance July 29, 2005, doi: 10.1101/gad.1311805 Genes & Dev. 19: 1840-1843 Cold Spring Harbor Laboratory Press

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