BACKGROUND: Mutations in the adenomatous polyposis coli (APC) tumour suppressor gene are implicated in the genesis of colorectal cancers. The product of the APC gene forms a complex with beta-catenin, glycogen synthase kinase 3beta (GSK-3beta) and Axin/conductin, and induces the degradation of beta-catenin. RESULTS: We have identified a novel Drosophila homologue of APC, E-APC, which is similar to but differs in several respects from D-APC. The E-APC cDNA encodes a protein of predicted 1067 amino acids, with seven armadillo repeats, two copies of the 15-amino acid repeat, five copies of the 20-amino acid repeat, and one Axin/conductin binding site. E-APC directly interacts with D-Axin and Armadillo (Arm, the Drosophila homologue of beta-catenin) in vitro, destabilizes intracellular beta-catenin, and suppresses beta-catenin/TCF-regulated transcription in APC-/- colon cancer cells. The E-APC mRNA is ubiquitously expressed throughout all developmental stages in Drosophila. CONCLUSION: Our findings suggest that E-APC may be universally involved in the regulation of the Wingless signalling pathway by down-regulating the level of Arm in Drosophila.
BACKGROUND: Mutations in the adenomatous polyposis coli (APC) tumour suppressor gene are implicated in the genesis of colorectal cancers. The product of the APC gene forms a complex with beta-catenin, glycogen synthase kinase 3beta (GSK-3beta) and Axin/conductin, and induces the degradation of beta-catenin. RESULTS: We have identified a novel Drosophila homologue of APC, E-APC, which is similar to but differs in several respects from D-APC. The E-APC cDNA encodes a protein of predicted 1067 amino acids, with seven armadillo repeats, two copies of the 15-amino acid repeat, five copies of the 20-amino acid repeat, and one Axin/conductin binding site. E-APC directly interacts with D-Axin and Armadillo (Arm, the Drosophila homologue of beta-catenin) in vitro, destabilizes intracellular beta-catenin, and suppresses beta-catenin/TCF-regulated transcription in APC-/- colon cancer cells. The E-APC mRNA is ubiquitously expressed throughout all developmental stages in Drosophila. CONCLUSION: Our findings suggest that E-APC may be universally involved in the regulation of the Wingless signalling pathway by down-regulating the level of Arm in Drosophila.