Fig. 6.
Wnt/β-catenin signaling and its role in drug metabolism. In the absence of agonistic Wnt signals, cytosolic β-catenin is phosphorylated by a cytosolic multi-protein complex and subsequently degraded in the proteasome. Wnt binding to FZD receptors impairs β-catenin degradation. As a consequence, the protein accumulates and translocates to the nucleus. Nuclear β-catenin interacts with TCF transcription factors and induces target gene transcription, e.g. nuclear receptors and certain drug-metabolizing enzymes. Cooperative interplay of β-catenin and nuclear receptors also contributes to the induction of drug-metabolizing enzymes, especially from the CYP and GST families