Down-regulation of beta-catenin by the colorectal tumor suppressor APC requires association with Axin and beta-catenin.
The tumor suppressor adenomatous polyposis coli (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. APC forms a complex with beta-catenin, Axin, and glycogen synthase kinase-3beta and induces the degradation of beta-catenin. In the present study, we examined whether APC association with Axin is required for degradation of beta-catenin. We found that a fragment of APC that induces beta-catenin degradation was rendered inactive by disruption of its Axin-binding sites. Also, overexpression of an Axin fragment spanning the regulator of the G-protein signaling domain inhibited APC-mediated beta-catenin degradation. An APC fragment with mutated beta-catenin-binding sites but intact Axin-binding sites also failed to induce degradation of beta-catenin. These results suggest that APC requires interaction with Axin and beta-catenin to down-regulate beta-catenin.
Kawahara
K
K
Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.
Morishita
T
T
Nakamura
T
T
Hamada
F
F
Toyoshima
K
K
Akiyama
T
T
D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D060466:Axin Protein; D001665:Binding Sites; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D019204:GTP-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019204:GTP-Binding Proteins