Adenomatous polyposis coli is down-regulated by the ubiquitin-proteasome pathway in a process facilitated by Axin.
Adenomatous polyposis coli (APC) protein and Axin form a complex that mediates the down-regulation of beta-catenin, a key effector of Wnt signaling. Truncation mutations in APC are responsible for familial and sporadic colorectal tumors due to failure in the down-regulation of beta-catenin. While the regulation of beta-catenin by APC has ... been extensively studied, the regulation of APC itself has received little attention. Here we show that the level of APC is down-regulated by the ubiquitin-proteasome pathway and that Wnt signaling inhibits the process. The domain responsible for the down-regulation and direct ubiquitination was identified. We also show an unexpected role for Axin in facilitating the ubiquitination-proteasome-mediated down-regulation of APC through the oligomerization of Axin. Our results suggest a new mechanism for the regulation of APC by Axin and Wnt signaling.
Mesh Terms:
Adenomatous Polyposis Coli Protein, Amino Acids, Animals, Binding Sites, Blotting, Western, Cell Line, Cell Nucleus, Culture Media, Conditioned, Cytoskeletal Proteins, Down-Regulation, Epitopes, Gene Deletion, Humans, Immunoblotting, Immunoprecipitation, Microscopy, Fluorescence, Plasmids, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Time Factors, Trans-Activators, Transfection, Ubiquitin, Up-Regulation, Wnt Proteins, Xenopus, Xenopus Proteins, beta Catenin
Adenomatous Polyposis Coli Protein, Amino Acids, Animals, Binding Sites, Blotting, Western, Cell Line, Cell Nucleus, Culture Media, Conditioned, Cytoskeletal Proteins, Down-Regulation, Epitopes, Gene Deletion, Humans, Immunoblotting, Immunoprecipitation, Microscopy, Fluorescence, Plasmids, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Time Factors, Trans-Activators, Transfection, Ubiquitin, Up-Regulation, Wnt Proteins, Xenopus, Xenopus Proteins, beta Catenin
J. Biol. Chem.
Date: Nov. 19, 2004
PubMed ID: 15355978
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