Harvey, K.F., Mattila, J., Sofer, A., Bennett, F.C., Ramsey, M.R., Ellisen, L.W., Puig, O., Hariharan, I.K. (2008). FOXO-regulated transcription restricts overgrowth of Tsc mutant organs. J. Cell Biol. 180(4): 691--696.
FlyBase ID
FBrf0203175
Publication Type
Research paper
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.
