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. 2005 May 20;308(5725):1181-4.
doi: 10.1126/science.1109083.

Functional interaction between beta-catenin and FOXO in oxidative stress signaling

Marieke A G Essers  1 , Lydia M M de Vries-Smits, Nick Barker, Paulien E Polderman, Boudewijn M T Burgering, Hendrik C Korswagen
Affiliations

Functional interaction between beta-catenin and FOXO in oxidative stress signaling

Marieke A G Essers et al. Science. .

Abstract

beta-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 beta-catenin with FOXO transcription factors, which are regulated by insulin and oxidative stress signaling. beta-Catenin binds directly to FOXO and enhances FOXO transcriptional activity in mammalian cells. In Caenorhabditis elegans, loss of the beta-catenin BAR-1 reduces the activity of the FOXO ortholog DAF-16 in dauer formation and life span. Association of beta-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 beta-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress.

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