Biochemical and Biophysical Research Communications, Vol.534, 720-726, 2021
Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway
Cu/Zn Superoxide Dismutase (Sod1) catalyzes the disproportionation of cytotoxic superoxide radicals (O-2(center dot-)) into oxygen (O-2) and hydrogen peroxide (H2O2), a key signaling molecule. In Saccharomyces cerevisiae, we previously discovered that Sodl participates in an H2O2-mediated redox signaling circuit that links nutrient availability to the control of energy metabolism. In response to glucose and O-2, Sod1-derived H2O2 stabilizes a pair of conserved plasma membrane kinases - yeast casein kinase 1 and 2 (Yck1/2) - that signal glycolytic growth and the repression of respiration. The Yck1/2 homolog in humans, casein kinase 1-gamma (CK1 gamma), is an integral component of the Wingless and Int-1 (Wnt) signaling pathway, which is essential for regulating cell fate and proliferation in early development and adult tissue and is dysregulated in many cancers. Herein, we establish the conservation of the SOD1/YCK1 redox signaling axis in humans by finding that SOD1 regulates CK1 gamma expression in human embryonic kidney 293 (HEK293) cells and is required for canonical Wnt signaling and Wnt-dependent cell proliferation. (C) 2020 Elsevier Inc. All rights reserved.