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

Authors: Essers MA; de Vries-Smits LM; Barker N; Polderman PE; Burgering BM; Korswagen HC

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.

Keywords: Animals; Animals, Genetically Modified; Caenorhabditis elegans/genetics/*metabolism/physiology; Caenorhabditis elegans Proteins/genetics/*metabolism; Carrier Proteins/genetics/metabolism; Cell Cycle; Cell Line; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p27; Cytoskeletal Proteins/chemistry/genetics/*metabolism; DNA-Binding Proteins/metabolism; Forkhead Transcription Factors; Humans; Hydrogen Peroxide/pharmacology; Immunoprecipitation; Insulin/pharmacology; Intracellular Signaling Peptides and Proteins/genetics/metabolism; Lithium Chloride/pharmacology; Longevity; Mice; Mutation; *Oxidative Stress; Receptor, Insulin/genetics/metabolism; *Signal Transduction; Superoxide Dismutase/metabolism; Trans-Activators/chemistry/genetics/*metabolism; Transcription Factors/*metabolism; Transfection; beta Catenin
Journal: Science (New York, N.Y.)
Volume: 308
Issue: 5725
Pages: 1181-4
Date: May 21, 2005
PMID: 15905404
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Essers MA, de Vries-Smits LM, Barker N, Polderman PE, Burgering BM, Korswagen HC (2005) Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science (New York, N.Y.) 308: 1181-4.

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