Fig. 1

The Wnt/β-catenin signalling pathway. a Wnt signalling OFF. The absence of Wnt ligand binding to the FZD receptor prevents the interaction between FZD and LRP5/6. The destruction complex which resides in the cytoplasm binds to and promotes degradation of free cytoplasmic β-catenin. Specifically, CK1 and GSK-3β phosphorylate β-catenin, targeting it for βTrCP-mediated ubiquitination and subsequent proteasome degradation. Within the nucleus, the transcriptional repressor, Groucho binds to TCF and inhibits its transcriptional activity. b Wnt signalling ON. Binding of a Wnt ligand to FZD and LRP5/6 promotes the recruitment of DVL and the destruction complex to the membrane. As a result, the destruction complex’s ability to phosphorylate and degrade cytoplasmic β-catenin is inhibited. Cytoplasmic β-catenin accumulates and is translocated into the nucleus where it displaces Groucho and binds to TCF. Together with co-activators, the transcription of downstream target genes is initiated