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 induces 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 binds to and activates the Tcf-4 transcription factor (reviewed in [1,2]). Here, we report the identification and genomic structure of APC homologues. Mammalian APC2, which closely resembles APC in overall domain structure, was functionally analyzed and shown to contain two SAMP domains, both of which are required for binding to conductin, Like APC, APC2 regulates the formation 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.