The beta-Catenin Destruction Complex

The Wnt/beta-catenin pathway is highly regulated to insure the correct temporal and spatial activation of its target genes. In the absence of a Wnt stimulus, the transcriptional coactivator beta-catenin is degraded by a multiprotein destruction complex that includes the tumor suppressors Axin and adenomatous polyposis coli (APC), the Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A (PP2A), and the E3-ubiquitin ligase beta-TrCP. The complex generates a beta-TrCP recognition site by phosphorylation of a conserved Ser/Thr-rich sequence near the beta-catenin amino terminus, a process that requires scaffolding of the kinases and beta-catenin by Axin. Ubiquitinated beta-catenin is degraded by the proteasome. The molecular mechanisms that underlie several aspects of destruction complex function are poorly understood, particularly the role of APC. Here we review the molecular mechanisms of destruction complex function and discuss several potential roles of APC in beta-catenin destruction.