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

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.