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


CONCLUSIONS
Axin interacts with beta-catenin, GSK-3beta and APC, and negatively regulates the Wnt signalling pathway, presumably by regulating the level of beta-catenin.
Nakamura
T
T
Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, Suita, Japan.
Hamada
F
F
Ishidate
T
T
Anai
K
K
Kawahara
K
K
Toyoshima
K
K
Akiyama
T
T
D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D019204:GTP-Binding Proteins