Publication Date:
2005-05-21
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Essers, Marieke A G -- de Vries-Smits, Lydia M M -- Barker, Nick -- Polderman, Paulien E -- Burgering, Boudewijn M T -- Korswagen, Hendrik C -- New York, N.Y. -- Science. 2005 May 20;308(5725):1181-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiological Chemistry and Center for Biomedical Genetics, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15905404" target="_blank"〉PubMed〈/a〉
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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