Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway

• Published in: Biochemical and biophysical research communications Vol. 534; pp. 720 - 726
• Main Authors: Chandrasekharan, Bindu, Montllor-Albalate, Claudia, Colin, Alyson E., Andersen, Joshua L., Jang, Young C., Reddi, Amit R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2021
• Subjects: Cancer; Casein Kinase I - metabolism; Cell Proliferation - physiology; Cu/Zn superoxide dismutase; Gene Expression Regulation; HEK293 Cells; Humans; Hydrogen peroxide; Reactive oxygen species; Redox signaling; RNA Interference; Superoxide; Superoxide Dismutase-1 - genetics; Superoxide Dismutase-1 - metabolism; Wnt signaling; Wnt Signaling Pathway - physiology; Reactive oxygen species; Wnt signaling; Hydrogen peroxide; Cu/Zn superoxide dismutase; Superoxide; Redox signaling; Cancer
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.11.011

Cu/Zn Superoxide Dismutase (Sod1) catalyzes the disproportionation of cytotoxic superoxide radicals (O2•-) into oxygen (O2) and hydrogen peroxide (H2O2), a key signaling molecule. In Saccharomyces cerevisiae, we previously discovered that Sod1 participates in an H2O2-mediated redox signaling circuit that links nutrient availability to the control of energy metabolism. In response to glucose and O2, 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-γ (CK1γ), 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 CK1γ expression in human embryonic kidney 293 (HEK293) cells and is required for canonical Wnt signaling and Wnt-dependent cell proliferation.
•Cu/Zn Superoxide Dismutase (Sod1) is a well conserved and abundant antioxidant enzyme.•Sod1 plays important roles in redox signaling due to its production of H2O2.•Sod1 regulates the canonical Wnt signaling pathway.