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FOXO-regulated transcription restricts overgrowth of Tsc mutant organs.

  • Author(s): Harvey, Kieran;
  • Mattila, Jaakko;
  • Sofer, Avi;
  • Bennett, F;
  • Ramsey, Matthew;
  • Ellisen, Leif;
  • Puig, Oscar;
  • HARIHARAN, Iswar Krishna
  • et al.
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.

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