Abstract
FOXO is thought to function as a repressor of growth that is, in turn, inhibited by insulin signaling. However, inactivating mutations in Drosophila melanogaster FOXO result in viable flies of normal size, which raises a question over the involvement of FOXO in growth regulation. Previously, a growth-suppressive role for FOXO under conditions of increased target of rapamycin (TOR) pathway activity was described. Here, we further characterize this phenomenon. We show that tuberous sclerosis complex 1 mutations cause increased FOXO levels, resulting in elevated expression of FOXO-regulated genes, some of which are known to antagonize growth-promoting pathways. Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Proliferation
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Congenital Abnormalities / genetics
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Drosophila Proteins / genetics*
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Drosophila melanogaster / cytology
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Drosophila melanogaster / embryology*
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Drosophila melanogaster / genetics*
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Female
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Forkhead Transcription Factors / genetics*
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Gene Expression Regulation, Developmental / genetics
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Growth Inhibitors / genetics
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Growth Inhibitors / metabolism
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Male
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Mutation / genetics*
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Organogenesis / genetics*
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Phosphatidylinositol 3-Kinases / genetics
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Protein Kinases
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Regulatory Elements, Transcriptional / genetics
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Species Specificity
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TOR Serine-Threonine Kinases
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Transcription, Genetic / genetics
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Up-Regulation / genetics
Substances
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Drosophila Proteins
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FOXO protein, Drosophila
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Forkhead Transcription Factors
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Growth Inhibitors
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TSC1 protein, Drosophila
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Protein Kinases
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target of rapamycin protein, Drosophila
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TOR Serine-Threonine Kinases