fig1
Figure 1. Canonical Wnt pathway in a cardiomyocyte of a Myh6-Cre-DspW/F mouse model. (1) Upon activation, β-catenin translocates to the nucleus. Its interaction with TCF/LEF activates the expression of a myriad of genes involved in cardiac fibrosis. (2) The inactivation of the canonical Wnt pathway leads β-catenin to proteasomal degradation. (3) Porcupine, a post-translational enzyme localized to the endoplasmic reticulum, palmitoylates Wnt ligands for subsequent transmembrane transport and secretion to the extracellular space. WNT974, a Porcupine inhibitor, blocks this key step thereby suppressing the canonical pathway central to the pathogenesis of arrhythmogenic cardiomyopathy.
