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, 3 (6), 395-403

Axin, an Inhibitor of the Wnt Signalling Pathway, Interacts With Beta-Catenin, GSK-3beta and APC and Reduces the Beta-Catenin Level

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Axin, an Inhibitor of the Wnt Signalling Pathway, Interacts With Beta-Catenin, GSK-3beta and APC and Reduces the Beta-Catenin Level

T Nakamura et al. Genes Cells.

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.

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