The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila

Nat Cell Biol. 2001 Jun;3(6):596-601. doi: 10.1038/35078571.

Abstract

The initiation factor 4E for eukaryotic translation (eIF4E) binds the messenger RNA 5'-cap structure and is important in the regulation of protein synthesis. Mammalian eIF4E activity is inhibited when the initiation factor binds to the translational repressors, the 4E-binding proteins (4E-BPS). Here we show that the Drosophila melanogaster 4E-BP (d4E-BP) is a downstream target of the phosphatidylinositol-3-OH kinase (PI(3)K) signal-transduction cascade, which affects the interaction of d4E-BP with eIF4E. Ectopic expression of a highly active d4E-BP mutant in wing-imaginal discs causes a reduction of wing size, brought about by a decrease in cell size and number. A marked reduction in cell size was also observed in post-mitotic cells. Expression of d4E-BP in the eye and wing together with PI(3)K or dAkt1, the serine/threonine kinase downstream of PI(3)K, resulted in suppression of the growth phenotype elicited by these kinases. Our results support a role for d4E-BP as an effector of cell growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Division / physiology
  • Cloning, Molecular
  • Drosophila Proteins
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Peptide Initiation Factors
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Protein Biosynthesis
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*

Substances

  • Carrier Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Peptide Initiation Factors
  • Phosphoproteins
  • Thor protein, Drosophila
  • Phosphatidylinositol 3-Kinases