ASSOCIATION BETWEEN WILD-TYPE AND MUTANT APC GENE-PRODUCTS

Germline mutations of the APC gene are responsible for familial adenom atous polyposis, an autosomal dominant inherited predisposition to col orectal tumors. Mutation of the APC gene is also an early, if not init iating, event for sporadic colorectal tumorigenesis. In both cases, al most all of the currently identified mutations of APC result in the tr uncation of the protein. In this study, we demonstrate that truncated APC proteins can associate with the wild type APC in vivo. Using in vi tro expression and immunoprecipitation, we show that the first 171 res idues of APC are sufficient for APC oligomerization and that the first 45 amino acids of APC is necessary for this interaction. These result s indicate that most mutant APC proteins should be able to bind to wil d type APC protein and perhaps inactivate it in a dominant negative ma nner.