FIGURE 2.

Schematic diagram of Wnt/β-catenin signaling pathway in inactivated, activated and deactivated states. In the quiescent Wnt/β-catenin-dependent pathway (Wnt Off), β-catenin undergoes continuous ubiquitination in the absence of Wnt protein by the destruction complex. In this state, Wnt target genes are suppressed by Groucho and TCF/LEF transcription factors. Upon Wnt binding to FZD receptors and the co-receptor Lrp5/6 and formed a ligand-receptor complex called the “signalosome,” which further recruit the intracellular Dvl and components of the destruction complex to the cell membrane (Wnt On). This would prohibit the formation of destruction complex and thus prevents the degradation of β-catenin and allowing its nuclear translocation. β-catenin would subsequently bind with TCF/LEF transcription factors to inhibit their DNA binding. Wnt target genes, such as Axin2 and Nkd1, are disinhibited to transcript. Some extracellular molecules could inhibit the formation of signalosome. For example, DKKs can competitively bind to LRP6, while sFRPs can directly bind to Wnt proteins and reduce the activity of signal transduction.