Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T
Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, Suita, Japan.
Genes Cells. 1998 Jun;3(6):395-403. doi: 10.1046/j.1365-2443.1998.00198.x.
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.
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.
Axin interacts with beta-catenin, GSK-3beta and APC, and negatively regulates the Wnt signalling pathway, presumably by regulating the level of beta-catenin.
Wnt/Wingless信号通路在胚胎发育和肿瘤发生过程中均发挥重要作用。β-连环蛋白和轴抑制蛋白分别是Wnt信号通路的正向和负向效应器。
我们发现轴抑制蛋白与β-连环蛋白及糖原合酶激酶-3β(GSK-3β)相互作用。此外,轴抑制蛋白的G蛋白信号调节(RGS)结构域的调控与结直肠癌抑癌基因腺瘤性息肉病大肠杆菌(APC)相关。在人结肠癌细胞系SW480中过表达轴抑制蛋白可导致β-连环蛋白水平急剧降低。轴抑制蛋白介导的β-连环蛋白减少需要与β-连环蛋白和GSK-3β相互作用。
轴抑制蛋白与β-连环蛋白、GSK-3β和APC相互作用,并可能通过调节β-连环蛋白水平对Wnt信号通路起负向调控作用。