Abstract
Background:
The Wnt/Wingless signalling pathway plays an important role in both embryonic development and tumorigenesis. Beta-catenin and Axin are positive and negative effectors of the Wnt signalling pathway, respectively.
Results:
We found that Axin interacts with beta-catenin and glycogen synthase kinase-3beta (GSK-3beta). Furthermore, the regulation of the G-protein signalling (RGS) domain of Axin is associated with the colorectal tumour suppressor adenomatous polyposis coli (APC). Overexpression of Axin in the human colorectal cancer cell line SW480 induced a drastic reduction in the level of -catenin. Interaction with beta-catenin and GSK-3beta was required for the Axin-mediated beta-catenin reduction.
Conclusion:
Axin interacts with beta-catenin, GSK-3beta and APC, and negatively regulates the Wnt signalling pathway, presumably by regulating the level of beta-catenin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenomatous Polyposis Coli Protein
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Axin Protein
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Binding Sites
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cytoskeletal Proteins / metabolism*
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GTP-Binding Proteins / physiology
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Gene Expression Regulation, Neoplastic
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Humans
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Protein Binding
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Proteins / genetics
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Proteins / metabolism
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Proteins / physiology*
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Proto-Oncogene Proteins / physiology*
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Repressor Proteins*
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Signal Transduction / physiology
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Trans-Activators*
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Tumor Cells, Cultured
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Wnt Proteins
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Zebrafish Proteins*
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beta Catenin
Substances
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Adenomatous Polyposis Coli Protein
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Axin Protein
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CTNNB1 protein, human
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Cytoskeletal Proteins
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Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Trans-Activators
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Wnt Proteins
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Zebrafish Proteins
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beta Catenin
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Glycogen Synthase Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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GTP-Binding Proteins