Functional Interaction Between ß-Catenin and FOXO in Oxidative Stress Signaling
- 20 May 2005
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 308 (5725), 1181-1184
- https://doi.org/10.1126/science.1109083
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.Keywords
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