Abstract
Wnt signaling has an important role in both embryonic development and tumorigenesis. beta-Catenin, a key component of the Wnt signaling pathway, interacts with the TCF/LEF family of transcription factors and activates transcription of Wnt target genes. Here, we identify a novel beta-catenin-interacting protein, ICAT, that was found to inhibit the interaction of beta-catenin with TCF-4 and represses beta-catenin-TCF-4-mediated transactivation. Furthermore, ICAT inhibited Xenopus axis formation by interfering with Wnt signaling. These results suggest that ICAT negatively regulates Wnt signaling via inhibition of the interaction between beta-catenin and TCF and is integral in development and cell proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Body Patterning / drug effects
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Cell Cycle Proteins*
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Cell Division
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Cytoskeletal Proteins / physiology
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Developmental / drug effects
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Gene Library
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Genes, Dominant
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Goosecoid Protein
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Homeodomain Proteins / metabolism
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Humans
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Immunoblotting
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Intracellular Signaling Peptides and Proteins
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Luciferases / metabolism
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Mice
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Molecular Sequence Data
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Muscle Proteins / physiology
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Mutagenesis
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Precipitin Tests
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Repressor Proteins*
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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 2 Protein
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Transcription Factors / metabolism
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
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Two-Hybrid System Techniques
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Wnt Proteins
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Xenopus / embryology
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Xenopus Proteins
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Zebrafish Proteins*
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beta Catenin
Substances
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Adaptor Proteins, Signal Transducing
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CTNNB1 protein, Xenopus
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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CTNNBIP1 protein, human
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Cell Cycle Proteins
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Ctnnbip1 protein, mouse
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Cytoskeletal Proteins
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GSC protein, human
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Goosecoid Protein
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Gsc protein, mouse
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Muscle Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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Tcf7l2 protein, mouse
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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beta Catenin
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tcf7l2 protein, Xenopus
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Luciferases