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

Department of Biochemistry and McGill Cancer Center, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Quebec H3G 1Y6, Canada.
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.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Amino Acid Sequence, Animals, Carrier Proteins, Cell Division, Cloning, Molecular, Drosophila Proteins, Drosophila melanogaster, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Peptide Initiation Factors, Phosphoproteins, Protein Biosynthesis, Sequence Homology, Amino Acid, Signal Transduction
Nat. Cell Biol. Jun. 01, 2001; 3(6);596-601 [PUBMED:11389445]
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