Figure 1

The canonical Wnt/β-catenin pathway. A) In absence of Wnt signal the destruction complex, formed by the scaffold Axin, APC and GSK3, phosphorilates (P) β-catenin that is then ubiquitinated and degraded via proteasome. In this state the expression of the gene target is repressed. B) In presence of Wnt ligand, the receptor Fzd and the co-receptor LRP5/6 transduce the signal activating Dvl. The destruction complex is inhibited and β-catenin accumulates in the cytoplasm and it translocates into the nucleus. It promotes the target gene expression by binding TCF/LEF and other co-activators. To date several studies identified small molecules (some of these are indicated in the yellow boxes) that can directly inhibit specific components of the Wnt pathway. APC = adenomatous polyposis coli; GSK3 = glycogen synthase kinase; TCF = T cell factor; Fzd = Frizzled receptor; Dvl = Dishevelled.