Figure 1.

Canonical Wnt/β-catenin signaling pathway: OFF state. In the absence of Wnt, β-catenin (β-cat) is constantly turned over by the destruction complex. The destruction complex is assembled and maintained by scaffolding proteins Axin and APC. While associated with this complex, β-catenin is sequentially phosphorylated by CK1 and GSK3; phosphorylated β-catenin is recognized by the E3 ubiquitin ligase complex (β-Trcp) and degraded. ON state. Wnt binding to LRP5/6 and Frizzled cell surface Wnt co-receptors initiates canonical signaling, leading to the recruitment of Dishevelled (Dvl) and release of β-catenin from the degradation complex. β-catenin translocates to the nucleus where it binds to the TCF complex. Wnt target genes are actively transcribed. Points of modulation by potential therapeutic molecules are shown in blue for activating molecules and red for inhibitory molecules.