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

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          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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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          May 20 2005
          : 308
          : 5725
          Affiliations
          [1 ] Department of Physiological Chemistry and Center for Biomedical Genetics, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, Netherlands.
          Article
          308/5725/1181
          10.1126/science.1109083
          15905404
          17f0c249-6d49-4147-832f-9d8f3813e001
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