Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor

The adenomatous polyposis coli (APC) tumour-suppressor protein controls the Wnt signalling pathway by forming a complex with glycogen synthase kinase 3 beta (GSK-3 beta), axin/conductin and beta-catenin. Complex formation ind uces the rapid degradation of beta-catenin, In colon carcinoma cells, loss of APC leads to the accumulation of beta-catenin in the nucleus, where it b inds to and activates the Tcf-4 transcription factor (reviewed in [1,2]). H ere, we report the identification and genomic structure of APC homologues. Mammalian APC2, which closely resembles APC in overall domain structure, wa s functionally analyzed and shown to contain two SAMP domains, both of whic h are required for binding to conductin, Like APC, APC2 regulates the forma tion of active beta-catenin-Tcf complexes, as demonstrated using transient transcriptional activation assays in APC(-/-) colon carcinoma cells. Human APC2 maps to chromosome 19p13.3. APC and APC2 may therefore have comparable functions in development and cancer.