Axin, an inhibitor of the Wnt signalling pathway, interacts with β-catenin, GSK-3β and APC and reduces the β-catenin level

被引:259
作者
Nakamura, T
Hamada, F
Ishidate, T
Anai, K
Kawahara, K
Toyoshima, K
Akiyama, T
机构
[1] Osaka Univ, Dept Oncogene Res, Inst Microbial Dis, Suita, Osaka 565, Japan
[2] Univ Tokyo, Inst Mol & Cellular Biosci, Dept Mol & Genet Informat, Bunkyo Ku, Tokyo 113, Japan
[3] Osaka Med Ctr Canc & Cardiovasc Dis, Higashinari Ku, Osaka 537, Japan
[4] JST, PRESTO, Tokyo, Japan
关键词
D O I
10.1046/j.1365-2443.1998.00198.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-3 beta (GSK-3 beta). 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 beta-catenin. Interaction with beta-catenin and GSK-3 beta was required for the Axin-mediated beta-catenin reduction. Conclusion: Axin interacts with beta-catenin, GSK-3 beta and APC, and negatively regulates the Wnt signalling pathway, presumably by regulating the level of beta-catenin.
引用
收藏
页码:395 / 403
页数:9
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