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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-10-31
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pubmed:databankReference |
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pubmed:abstractText |
Beta-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the beta-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. We have determined the crystal structure at 2.5 A resolution of a complex between beta-catenin and ICAT, a protein that prevents the interaction between beta-catenin and Tcf/Lef family transcription factors. ICAT contains a 3-helix bundle that binds armadillo repeats 10-12 and a C-terminal tail that, similar to Tcf and E-cadherin, binds in the groove formed by armadillo repeats 5-9 of beta-catenin. We show that ICAT selectively inhibits beta-catenin/Tcf binding in vivo, without disrupting beta-catenin/cadherin interactions. Thus, it should be possible to design cancer therapeutics that inhibit beta-catenin-mediated transcriptional activation without interfering with cell adhesion.
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pubmed:grant |
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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/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNBIP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Xenopus Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Zebrafish Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/beta-catenin protein, Xenopus
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
563-71
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12408824-Amino Acid Sequence,
pubmed-meshheading:12408824-Animals,
pubmed-meshheading:12408824-Cell Adhesion,
pubmed-meshheading:12408824-Cell Cycle Proteins,
pubmed-meshheading:12408824-Crystallography, X-Ray,
pubmed-meshheading:12408824-Cytoskeletal Proteins,
pubmed-meshheading:12408824-DNA-Binding Proteins,
pubmed-meshheading:12408824-Humans,
pubmed-meshheading:12408824-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12408824-Macromolecular Substances,
pubmed-meshheading:12408824-Models, Molecular,
pubmed-meshheading:12408824-Muscle Proteins,
pubmed-meshheading:12408824-Neoplasms,
pubmed-meshheading:12408824-Protein Binding,
pubmed-meshheading:12408824-Protein Structure, Tertiary,
pubmed-meshheading:12408824-Proto-Oncogene Proteins,
pubmed-meshheading:12408824-Repressor Proteins,
pubmed-meshheading:12408824-Sequence Alignment,
pubmed-meshheading:12408824-Signal Transduction,
pubmed-meshheading:12408824-Trans-Activators,
pubmed-meshheading:12408824-Transcription Factors,
pubmed-meshheading:12408824-Transcriptional Activation,
pubmed-meshheading:12408824-Wnt Proteins,
pubmed-meshheading:12408824-Xenopus Proteins,
pubmed-meshheading:12408824-Xenopus laevis,
pubmed-meshheading:12408824-Zebrafish Proteins,
pubmed-meshheading:12408824-beta Catenin
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pubmed:year |
2002
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pubmed:articleTitle |
The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT.
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pubmed:affiliation |
Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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