title: The APC protein and E-cadherin form similar but independent complexes with alpha-catenin, beta-catenin, and plakoglobin.
abstract: The tumor suppressor APC protein associates with the cadherin-binding proteins alpha- and beta-catenin. To examine the relationship between cadherin, catenins, and APC, we have tested combinatorial protein-protein interactions in vivo, using a yeast two-hybrid system, and in vitro, using purified proteins. beta-Catenin directly binds to APC at high and low affinity sites. alpha-Catenin cannot directly bind APC but associates with it by binding to beta-catenin. Plakoglobin, also known as gamma-catenin, directly binds to both APC and alpha-catenin and also to the APC-beta-catenin complex, but not directly to beta-catenin. beta-Catenin binds to multiple independent regions of APC, some of which include a previously identified consensus motif and others which contain the centrally located 20 amino acid repeat sequences. The APC binding site on beta-catenin may be discontinuous since neither the carboxyl- nor amino-terminal halves of beta-catenin will independently associate with APC, although the amino-terminal half independently binds alpha-catenin. The catenins bind to APC and E-cadherin in a similar fashion, but APC and E-cadherin do not associate with each other either in the presence or absence of catenins. Thus, APC forms distinct heteromeric complexes containing combinations of alpha-catenin, beta-catenin, and plakoglobin which are independent from the cadherin-catenin complexes.
authors.affiliation: Onyx Pharmaceuticals, Richmond, California 94806.
authors.forename: B
authors.initials: B
authors.lastname: Rubinfeld
authors.forename: B
authors.initials: B
authors.lastname: Souza
authors.forename: I
authors.initials: I
authors.lastname: Albert
authors.forename: S
authors.initials: S
authors.lastname: Munemitsu
authors.forename: P
authors.initials: P
authors.lastname: Polakis
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051180:Desmoplakins; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015723:Gene Library; D016147:Genes, Tumor Suppressor; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D010179:Pancreas / Q000378:metabolism; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin