Abstract
Axin forms a complex with adenomatous polyposis coli gene product, glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, Dvl, and protein phosphatase 2A and functions as a scaffold protein in the Wnt signaling pathway. In the Axin complex, GSK-3beta efficiently phosphorylates beta-catenin, which is then ubiquitinated and degraded by proteasome. We isolated a novel protein that binds to Axin and named it Axam (for Axin associating molecule). Axam formed a complex with Axin in intact cells and bound directly to Axin. Axam inhibited the complex formation of Dvl with Axin and the activity of Dvl to suppress GSK-3beta-dependent phosphorylation of Axin. Furthermore, Axam induced the degradation of beta-catenin in SW480 cells and inhibited Wnt-dependent axis duplication in Xenopus embryos. These results suggest that Axam regulates the Wnt signaling pathway negatively by inhibiting the binding of Dvl to Axin.
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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Axin Protein
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / metabolism*
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Cytoskeletal Proteins / metabolism
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Electrophoresis, Polyacrylamide Gel
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Molecular Sequence Data
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Phosphorylation
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Protein Conformation
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Proteins / metabolism*
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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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Trans-Activators*
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Wnt Proteins
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Xenopus
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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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Axin Protein
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CTNNB1 protein, Xenopus
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Carrier Proteins
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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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Senp2 protein, rat
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Trans-Activators
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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axin1 protein, Xenopus
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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