
pmid: 18177722
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.
PROTEINS, Physiology, Immunoblotting, HUMDISEASE, Models, Biological, Animals, Genetically Modified, Proto-Oncogene Proteins c-myc, Phosphatidylinositol 3-Kinases, Animals, Drosophila Proteins, Immunoprecipitation, Insulin, Molecular Biology, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Mitogen-Activated Protein Kinase Kinases, Gene Expression Profiling, Forkhead Transcription Factors, Cell Biology, Fasting, Eukaryotic Initiation Factor-4E, SIGNALING, Protein Biosynthesis, Drosophila, Electrophoresis, Polyacrylamide Gel, Protein Kinases
PROTEINS, Physiology, Immunoblotting, HUMDISEASE, Models, Biological, Animals, Genetically Modified, Proto-Oncogene Proteins c-myc, Phosphatidylinositol 3-Kinases, Animals, Drosophila Proteins, Immunoprecipitation, Insulin, Molecular Biology, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Mitogen-Activated Protein Kinase Kinases, Gene Expression Profiling, Forkhead Transcription Factors, Cell Biology, Fasting, Eukaryotic Initiation Factor-4E, SIGNALING, Protein Biosynthesis, Drosophila, Electrophoresis, Polyacrylamide Gel, Protein Kinases
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