FOXO-regulated transcription restricts overgrowth of Tsc mutant organs

Kieran F. Harvey, Jaakko Mattila, Avi Sofer, F. Christian Bennett, Matthew R. Ramsey, Leif W. Ellisen, Oscar Puig, Iswar K. Hariharan

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)691-696
Number of pages6
JournalJournal of Cell Biology
Volume180
Issue number4
DOIs
Publication statusPublished - 25 Feb 2008

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