A DROSOPHILA HOMOLOG OF THE TUMOR-SUPPRESSOR GENE ADENOMATOUS POLYPOSIS-COLI DOWN-REGULATES BETA-CATENIN BUT ITS ZYGOTIC EXPRESSION IS NOT ESSENTIAL FOR THE REGULATION OF ARMADILLO

Mutations in the adenomatous polyposis coli gene (which encodes a prot ein called APC) are associated with the formation of intestinal polyps and colon cancers, To facilitate the functional study of APC we have isolated its Drosophila homolog (D-APC) by screening an expression lib rary with an antibody against human APC. The isolated cDNA encodes a p redicted 2416-amino acid protein containing significant homology to mu ltiple domains of mammalian APCs. D-APC has seven complete armadillo r epeats with 60% identity to its human homolog, one beta-catenin bindin g site, and up to 7 copies of a 20-amino acid repeat with the average of 50% identity to human APC at amino acid level, D-APC, like its huma n counterpart, also contains a basic domain, Expression of the domain of D-APC homologous to the region required for beta-catenin down-regul ation resulted in down-regulation of intracellular beta-catenin in a m ammalian cell line, This same region bound to the Armadillo (Arm) prot ein, in vitro, the Drosophila homolog of beta-catenin, D-APC RNA and p rotein expression is very low, if detectable at all, during stages whe n Arm protein accumulates in a striped pattern in the epidermis of the Drosophila embryos, Removing zygotic D-APC expression did not alter A rm protein distribution, and the final cuticle pattern was not affecte d significantly. As observed in the rodent, high levels of D-APC expre ssion have been detected in the central nervous system, suggesting a r ole for D-APC in central nervous system formation.