THE APC PROTEIN AND E-CADHERIN FORM SIMILAR BUT INDEPENDENT COMPLEXESWITH ALPHA-CATENIN, BETA-CATENIN, AND PLAKOGLOBIN

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-prot ein interactions in vivo, using a yeast two-hybrid system, and in vitr o, using purified proteins. beta-Catenin directly binds to APC at high and low affinity sites. alpha-Catenin cannot directly bind APC but as sociates with it by binding to beta-catenin. Plakoglobin, also known a s gamma-catenin, directly binds to both APC and alpha-catenin and also to the APC beta-catenin complex, but not directly to beta-catenin. be ta-Catenin binds to multiple independent regions of APC, some of which include a previously identified consensus motif and others which cont ain the centrally located 20 amino acid repeat sequences. The APC bind ing site on beta-catenin may be discontinuous since neither the carbox yl- nor amino-terminal halves of beta-catenin will independently assoc iate with APC, although the aminoterminal half independently binds alp ha-catenin. The catenins bind to APC and E-cadherin in a similar fashi on, but APC and E-cadherin do not associate with each other either in the presence or absence of catenins. Thus, APC forms distinct heterome ric complexes containing combinations of alpha catenin, beta-catenin, and plakoglobin which are independent from the cadherin-catenin comple xes.