The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila.
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.
Miron
M
M
Department of Biochemistry and McGill Cancer Center, McGill University, 3655 Promenade Sir-William-Osler, Montréal, Québec H3G 1Y6, Canada.
Verdú
J
J
Lachance
P E
PE
Birnbaum
M J
MJ
Lasko
P F
PF
Sonenberg
N
N
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; C410006:Thor protein, Drosophila; D019869:Phosphatidylinositol 3-Kinases