Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila

Cell Metab. 2008 Jan;7(1):21-32. doi: 10.1016/j.cmet.2007.11.010.

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
  • Phosphatidylinositol 3-Kinases
  • target of rapamycin protein, Drosophila
  • TOR Serine-Threonine Kinases
  • Lk6 protein, Drosophila
  • Mitogen-Activated Protein Kinase Kinases