Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Body Patterning, Cell Cycle Proteins, Cell Division, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Gene Expression Regulation, Developmental, Gene Library, Genes, Dominant, Goosecoid Protein, Homeodomain Proteins, Humans, Immunoblotting, Intracellular Signaling Peptides and Proteins, Luciferases, Mice, Molecular Sequence Data, Muscle Proteins, Mutagenesis, Precipitin Tests, Proto-Oncogene Proteins, Repressor Proteins, Signal Transduction, TCF Transcription Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Two-Hybrid System Techniques, Wnt Proteins, Xenopus, Xenopus Proteins, Zebrafish Proteins, beta Catenin
Amino Acid Sequence, Animals, Body Patterning, Cell Cycle Proteins, Cell Division, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Gene Expression Regulation, Developmental, Gene Library, Genes, Dominant, Goosecoid Protein, Homeodomain Proteins, Humans, Immunoblotting, Intracellular Signaling Peptides and Proteins, Luciferases, Mice, Molecular Sequence Data, Muscle Proteins, Mutagenesis, Precipitin Tests, Proto-Oncogene Proteins, Repressor Proteins, Signal Transduction, TCF Transcription Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Two-Hybrid System Techniques, Wnt Proteins, Xenopus, Xenopus Proteins, Zebrafish Proteins, beta Catenin
Genes Dev.
Date: Jul. 15, 2000
PubMed ID: 10898789
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