Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila.
Animals use the insulin/TOR signaling pathway to mediate their response to fluctuations in nutrient availability. Energy and amino acids are monitored at the single-cell level via the TOR branch of the pathway and systemically via insulin signaling to regulate cellular growth and metabolism. Using a combination of genetics, expression profiling, and chromatin immunoprecipitation, we examine nutritional control of gene expression and identify the transcription factor Myc as an important mediator of TOR-dependent regulation of ribosome biogenesis. We also identify myc as a direct target of FOXO and provide genetic evidence that Myc has a key role in mediating the effects of TOR and FOXO on growth and metabolism. FOXO and TOR also converge to regulate protein synthesis, acting via 4E-BP and Lk6, regulators of the translation factor eIF4E. This study uncovers a network of convergent regulation of protein biosynthesis by the FOXO and TOR branches of the nutrient-sensing pathway.
Teleman
Aurelio A
AA
EMBL, Meyerhofstrasse 1, Heidelberg, Germany.
Hietakangas
Ville
V
Sayadian
Aram C
AC
Cohen
Stephen M
SM
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D005215:Fasting; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015151:Immunoblotting; D047468:Immunoprecipitation; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D011494:Protein Kinases; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D051858:Forkhead Transcription Factors; D007328:Insulin; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D016271:Proto-Oncogene Proteins c-myc; D058570:TOR Serine-Threonine Kinases; C477334:FOXO protein, Drosophila; C416303:target of rapamycin protein, Drosophila; C500415:Lk6 protein, Drosophila