Abstract
The Wnt signaling pathway plays critical roles in embryonic development and tumorigenesis. Stimulation of the Wnt pathway results in the accumulation of a nuclear beta-catenin/Tcf complex, activating Wnt target genes. A crystal structure of beta-catenin bound to the beta-catenin binding domain of Tcf3 (Tcf3-CBD) has been determined. The Tcf3-CBD forms an elongated structure with three binding modules that runs antiparallel to beta-catenin along the positively charged groove formed by the armadillo repeats. Structure-based mutagenesis defines three sites in beta-catenin that are critical for binding the Tcf3-CBD and are differentially involved in binding APC, cadherin, and Axin. The structural and mutagenesis data reveal a potential target for molecular drug design studies.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Axin Protein
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Cadherins / metabolism
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Crystallography, X-Ray
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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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HMGB Proteins*
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Humans
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Precipitin Tests
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Protein Binding
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Protein Conformation*
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Proteins / metabolism
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Repressor Proteins*
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Sequence Alignment
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Signal Transduction
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TCF Transcription Factors
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Trans-Activators*
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / chemistry
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Transcription Factors / metabolism*
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Xenopus
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Xenopus Proteins
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beta Catenin
Substances
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Axin Protein
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CTNNB1 protein, Xenopus
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CTNNB1 protein, human
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Cadherins
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Cytoskeletal Proteins
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HMGB Proteins
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Proteins
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Repressor Proteins
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TCF Transcription Factors
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TCF7L1 protein, human
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Trans-Activators
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Transcription Factor 7-Like 1 Protein
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Transcription Factors
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Xenopus Proteins
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axin1 protein, Xenopus
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beta Catenin