FOXO-regulated Transcription Restricts Overgrowth of Tsc Mutant Organs

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2008 Feb 27

PMID 18299344

Citations 23

Authors

Kieran F Harvey

Jaakko Mattila

Avi Sofer

F Christian Bennett

Matthew R Ramsey

Leif W Ellisen

Oscar Puig

Iswar K Hariharan

Affiliations

Soon will be listed here.

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.

Citing Articles

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FoxO suppresses endoplasmic reticulum stress to inhibit growth of Tsc1-deficient tissues under nutrient restriction.

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