fig8

Figure 8. Schematic diagram of the proposed signaling mechanism that stimulates EMT and cardiomyogenesis. GSNOR loss of function results in GSNO accumulation and increased S-nitrosylation and reduced activity of GSK-3β, a protein that targets Snail/Slug/Twist and β-catenin for degradation through the ubiquitin proteosome pathway. This increased β-catenin and Snail/Slug/Twist represses E-cadherin, promotes β-catenin association with TCL/LEF complexes, augmenting transcription of proliferation, migration, EMT, and other target genes, resulting in elevated levels of Nkx2.5 mRNA levels and accelerating cardiomyogenesis.