Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Animals, Genetically Modified
-
Cells, Cultured
-
Drosophila / cytology
-
Drosophila / genetics
-
Drosophila / metabolism*
-
Drosophila Proteins / genetics
-
Drosophila Proteins / metabolism*
-
Electrophoresis, Polyacrylamide Gel
-
Eukaryotic Initiation Factor-4E / genetics
-
Eukaryotic Initiation Factor-4E / metabolism
-
Fasting
-
Forkhead Transcription Factors / genetics
-
Forkhead Transcription Factors / metabolism
-
Gene Expression Profiling
-
Immunoblotting
-
Immunoprecipitation
-
Insulin / genetics
-
Insulin / metabolism*
-
Mitogen-Activated Protein Kinase Kinases / genetics
-
Mitogen-Activated Protein Kinase Kinases / metabolism
-
Models, Biological
-
Oligonucleotide Array Sequence Analysis
-
Phosphatidylinositol 3-Kinases / genetics
-
Phosphatidylinositol 3-Kinases / metabolism
-
Protein Biosynthesis*
-
Protein Kinases
-
Proto-Oncogene Proteins c-myc / genetics
-
Proto-Oncogene Proteins c-myc / metabolism*
-
Signal Transduction
-
TOR Serine-Threonine Kinases
-
Transcription, Genetic
Substances
-
Drosophila Proteins
-
Eukaryotic Initiation Factor-4E
-
FOXO protein, Drosophila
-
Forkhead Transcription Factors
-
Insulin
-
Proto-Oncogene Proteins c-myc
-
Protein Kinases
-
target of rapamycin protein, Drosophila
-
TOR Serine-Threonine Kinases
-
Lk6 protein, Drosophila
-
Mitogen-Activated Protein Kinase Kinases