Journal Article

Functional Interaction between β-Catenin and FOXO in Oxidative Stress Signaling

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

2005

Overview

β-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 evolutionary conserved interaction of β-catenin with FOXO transcription factors, which are regulated by insulin and oxidative stress signaling. β-Catenin binds directly to FOXO and enhances FOXO transcriptional activity in mammalian cells. In Caenorhabditis elegans, loss of the β-catenin BAR-1 reduces the activity of the FOXO ortholog DAF-16 in dauer formation and life span. Association of β-catenin with FOXO was enhanced in cells exposed to oxidative stress. Furthermore, BAR-1 was required for the oxidative stressinduced expression of the DAF-16 target gene sod-3 and for resistance to oxidative damage. These results demonstrate a role for β-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress.

• Publisher: American Association for the Advancement of Science
• Subject: Animals / Animals, Genetically Modified / beta Catenin / Biological and medical sciences / Caenorhabditis elegans / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Caenorhabditis elegans - physiology / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cell Cycle / Cell Line / Cell Line, Tumor / Cyclin-Dependent Kinase Inhibitor p27 / Cytoskeletal Proteins - chemistry / Cytoskeletal Proteins - genetics / Cytoskeletal Proteins - metabolism / DNA-Binding Proteins - metabolism / Forkhead Box Protein O1 / Forkhead Transcription Factors / Fundamental and applied biological sciences. Psychology / Gene expression regulation / Genetic transcription / HEK293 cells / Humans / Hydrogen Peroxide - pharmacology / Immunoprecipitation / Insulin / Insulin - pharmacology / Intracellular Signaling Peptides and Proteins - genetics / Intracellular Signaling Peptides and Proteins - metabolism / Journalism / Life span / Lithium Chloride - pharmacology / Longevity / Mice / Molecular and cellular biology / Molecular genetics / Mutation / Nematode larvae / Oxidative Stress / Receptor, Insulin - genetics / Receptor, Insulin - metabolism / Signal Transduction / Small interfering RNA / Superoxide Dismutase - metabolism / T lymphocytes / Trans-Activators - chemistry / Trans-Activators - genetics / Trans-Activators - metabolism / Transcription (Genetics) / Transcription Factors - metabolism / Transcription. Transcription factor. Splicing. Rna processing / Transfection