title: The β-catenin destruction complex.
abstract: The Wnt/β-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 β-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 β-TrCP. The complex generates a β-TrCP recognition site by phosphorylation of a conserved Ser/Thr-rich sequence near the β-catenin amino terminus, a process that requires scaffolding of the kinases and β-catenin by Axin. Ubiquitinated β-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 β-catenin destruction.
authors.affiliation: Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stamos
authors.forename: William I
authors.initials: WI
authors.lastname: Weis
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000737:chemistry / Q000502:physiology; D000595:Amino Acid Sequence; D060466:Axin Protein / Q000378:metabolism / Q000502:physiology; D060465:Axin Signaling Complex / Q000502:physiology*; D001665:Binding Sites; D005786:Gene Expression Regulation; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D054875:Ubiquitination; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; D060465:Axin Signaling Complex; D051176:beta Catenin; D046988:Proteasome Endopeptidase Complex