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

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.
Mesh Terms:
Animals, Animals, Genetically Modified, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Carrier Proteins, Cell Cycle, Cell Line, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p27, Cytoskeletal Proteins, DNA-Binding Proteins, Forkhead Transcription Factors, Humans, Hydrogen Peroxide, Immunoprecipitation, Insulin, Intracellular Signaling Peptides and Proteins, Lithium Chloride, Longevity, Mice, Mutation, Oxidative Stress, Receptor, Insulin, Signal Transduction, Superoxide Dismutase, Trans-Activators, Transcription Factors, Transfection, beta Catenin
Science
Date: May. 20, 2005
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