Functional Interaction Between ß-Catenin and FOXO in Oxidative Stress Signaling

Abstract

β-Catenin is a multifunctional protein that mediates Wnt signaling by binding to members of the T cell factor (TCF) family of transcription factors. Here, we report an evolutionarily conserved interaction of β-catenin with FOXO transcription factors, which are regulated by insulin and oxidative stress signaling. β-Catenin binds directly to FOXO and enhances FOXO transcriptional activity in mammalian cells. In Caenorhabditis elegans , loss of the β-catenin BAR-1 reduces the activity of the FOXO ortholog DAF-16 in dauer formation and life span. Association of β-catenin with FOXO was enhanced in cells exposed to oxidative stress. Furthermore, BAR-1 was required for the oxidative stress–induced expression of the DAF-16 target gene sod-3 and for resistance to oxidative damage. These results demonstrate a role for β-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress.