rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1999-6-24
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pubmed:abstractText |
Regulation of beta-catenin stability is essential for Wnt signal transduction during development and tumorigenesis. It is well known that serine-phosphorylation of beta-catenin by the Axin-glycogen synthase kinase (GSK)-3beta complex targets beta-catenin for ubiquitination-degradation, and mutations at critical phosphoserine residues stabilize beta-catenin and cause human cancers. How beta-catenin phosphorylation results in its degradation is undefined. Here we show that phosphorylated beta-catenin is specifically recognized by beta-Trcp, an F-box/WD40-repeat protein that also associates with Skp1, an essential component of the ubiquitination apparatus. beta-catenin harboring mutations at the critical phosphoserine residues escapes recognition by beta-Trcp, thus providing a molecular explanation for why these mutations cause beta-catenin accumulation that leads to cancer. Inhibition of endogenous beta-Trcp function by a dominant negative mutant stabilizes beta-catenin, activates Wnt/beta-catenin signaling, and induces axis formation in Xenopus embryos. Therefore, beta-Trcp plays a central role in recruiting phosphorylated beta-catenin for degradation and in dorsoventral patterning of the Xenopus embryo.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10339577-10096067,
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Axin Protein,
http://linkedlifedata.com/resource/pubmed/chemical/BTRC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Xenopus Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/axin1 protein, Xenopus,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/beta-TrCP protein, Xenopus,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Transducin Repeat-Containing...,
http://linkedlifedata.com/resource/pubmed/chemical/beta-catenin protein, Xenopus
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6273-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10339577-Animals,
pubmed-meshheading:10339577-Axin Protein,
pubmed-meshheading:10339577-Body Patterning,
pubmed-meshheading:10339577-Cadherins,
pubmed-meshheading:10339577-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10339577-Carrier Proteins,
pubmed-meshheading:10339577-Cytoskeletal Proteins,
pubmed-meshheading:10339577-Embryo, Nonmammalian,
pubmed-meshheading:10339577-GTP-Binding Proteins,
pubmed-meshheading:10339577-Glycogen Synthase Kinase 3,
pubmed-meshheading:10339577-Humans,
pubmed-meshheading:10339577-Microtubule-Associated Proteins,
pubmed-meshheading:10339577-Phosphorylation,
pubmed-meshheading:10339577-Proteins,
pubmed-meshheading:10339577-Recombinant Fusion Proteins,
pubmed-meshheading:10339577-Repressor Proteins,
pubmed-meshheading:10339577-Signal Transduction,
pubmed-meshheading:10339577-Trans-Activators,
pubmed-meshheading:10339577-Transcription, Genetic,
pubmed-meshheading:10339577-Xenopus Proteins,
pubmed-meshheading:10339577-Xenopus laevis,
pubmed-meshheading:10339577-beta Catenin,
pubmed-meshheading:10339577-beta-Transducin Repeat-Containing Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation.
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pubmed:affiliation |
Division of Neuroscience, Children's Hospital, Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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