Schematic diagram showing that H2 promotes phosphorylation and degradation of β-catenin in activated Wnt/β-catenin signaling.
β-catenin is phosphorylated at one site by CK1 and at three sites by GSK3 in the degradation complex composed of CK1, GSK3, APC and Axin1. Wnt3a or BIO inhibits phosphorylation and ubiquitination of β-catenin and increases the intracellular level of β-catenin, which drives Wnt/β-catenin signaling from the “off-state” to the “on-state”. H2 works on the degradation complex to enhance phosphorylation and degradation of β-catenin when Wnt/β-catenin signaling is activated by Wnt3a or BIO and moves the “on-state” toward the “off-state”. H2 has no direct effect on the protein phosphatase 2A (not shown) or the ubiquitination process.