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PMID:18177722

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Citation

Teleman, AA, Hietakangas, V, Sayadian, AC and Cohen, SM (2008) Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila. Cell Metab. 7:21-32

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.

Links

PubMed Online version:10.1016/j.cmet.2007.11.010

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q9U9A9

involved_in

GO:0048640: negative regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VCC9

involved_in

GO:0048640: negative regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:MYC

involved_in

GO:0048639: positive regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:FOXO

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:FOXO

involved_in

GO:0009267: cellular response to starvation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:FOXO

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

Notes

See also

References

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