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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans / physiology
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Cycle
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Cell Cycle Proteins
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Cell Line
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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p27
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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DNA-Binding Proteins / metabolism
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Humans
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Hydrogen Peroxide / pharmacology
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Immunoprecipitation
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Insulin / pharmacology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Lithium Chloride / pharmacology
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Longevity
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Mice
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Mutation
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Oxidative Stress*
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Receptor, Insulin / genetics
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Receptor, Insulin / metabolism
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Signal Transduction*
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Superoxide Dismutase / metabolism
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / metabolism*
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Transfection
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beta Catenin
Substances
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CDKN1B protein, human
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cell Cycle Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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FOXO1 protein, human
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FOXO4 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Insulin
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Intracellular Signaling Peptides and Proteins
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Trans-Activators
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Transcription Factors
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bar-1 protein, C elegans
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beta Catenin
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daf-16 protein, C elegans
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Cyclin-Dependent Kinase Inhibitor p27
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Hydrogen Peroxide
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Superoxide Dismutase
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DAF-2 protein, C elegans
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Receptor, Insulin
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Lithium Chloride