The APC gene, and possible pathogenetic mechanisms in familial adenomatous polyposis

The APC (adenomatous polyposis coli) gene modulates β-catenin, Tcf transcriptional activation, and Wnt signal transduction.
(A) In the presence of wildtype APC or in the absence of Wnt ligand, β-catenin is localized to the adherens junction where it is associated with E-cadherin, α-catenin, p120cas, and indirectly with the cytoskeleton. GSK3β phosphorylates β-catenin in a complex that contains β-catenin, APC, and axin family members, and β-catenin is rapidly degraded by ubiquination at the proteosome.
(B) When APC is mutated, β-catenin accumulates in the cytoplasm and the nucleus. Similarly, binding of Wnt ligand to its receptor, known as frizzled, inactivates the GSK3β kinase through dishevelled, generating a cytosolic pool of β-catenin. β-catenin is associated with members of the Tcf family of transcription factors and modulates the transcription of target genes with Tcf recognition sequences. In some instances, β-catenin increases transcription of target genes by competing for Tcf binding with corepressors, such as Groucho and CREB-binding protein (CBP), to relieve transcriptional repression.