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Science 308 (5725): 1181-1184

Copyright © 2005 by the American Association for the Advancement of Science

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

Marieke A. G. Essers,1 Lydia M. M. de Vries-Smits,1 Nick Barker,2 Paulien E. Polderman,1 Boudewijn M. T. Burgering,1* Hendrik C. Korswagen2*

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

1 Department of Physiological Chemistry and Center for Biomedical Genetics, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, Netherlands.
2 Hubrecht Laboratory and Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, Netherlands.

* To whom correspondence should be addressed. E-mail: b.m.t.burgering{at}med.uu.nl and rkors{at}niob.knaw.nl

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