Abstract
When Axin, a negative regulator of the Wnt signaling pathway, was expressed in COS cells, it coeluted with glycogen synthase kinase-3β (GSK-3β), β-catenin, and adenomatous polyposis coli protein (APC) in a high molecular weight fraction on gel filtration column chromatography. In this fraction, GSK-3β, β-catenin, and APC were co-precipitated with Axin. Although β-catenin was detected in the high molecular weight fraction in L cells on gel filtration column chromatography, addition of conditioned medium expressing Wnt-3a to the cells increased β-catenin in the low molecular weight fraction. However, Wnt-3a-dependent accumulation of β-catenin was greatly inhibited in L cells stably expressing Axin. Axin also suppressed Wnt-3a-dependent activation of Tcf-4 which binds to β-catenin and acts as a transcription factor. These results suggest that Axin forms a complex with GSK-3β, β-catenin, and APC, resulting in the stimulation of the degradation of β-catenin and that Wnt-3a induces the dissociation of β-catenin from the Axin complex and accumulates β-catenin.
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Acknowledgements
We are grateful to Drs A Nagafuchi, S Tsukita, E Tahara, M van de Wetering and H Clevers for their plasmids and cells. We wish to thank the Research Center for Molecular Medicine and Research Facilities for Laboratory Animal Sciences, Hiroshima University School of Medicine, for the use of their facilities. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Science, and Culture, Japan (1997, 1998), and by grants from Yamanouchi Foundation for Research on Metabolic Disorders (1997), Kato Memorial Bioscience Foundation (1997), and the Naito Foundation (1997).
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Kishida, M., Koyama, S., Kishida, S. et al. Axin prevents Wnt-3a-induced accumulation of β-catenin. Oncogene 18, 979–985 (1999). https://doi.org/10.1038/sj.onc.1202388
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DOI: https://doi.org/10.1038/sj.onc.1202388
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