铜锌超氧化物歧化酶（Sod1）调节经典 Wnt 信号通路。
Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway.
机构信息
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA.
出版信息
Biochem Biophys Res Commun. 2021 Jan 1;534:720-726. doi: 10.1016/j.bbrc.2020.11.011. Epub 2020 Nov 18.
Cu/Zn Superoxide Dismutase (Sod1) catalyzes the disproportionation of cytotoxic superoxide radicals (O) into oxygen (O) and hydrogen peroxide (HO), a key signaling molecule. In Saccharomyces cerevisiae, we previously discovered that Sod1 participates in an HO-mediated redox signaling circuit that links nutrient availability to the control of energy metabolism. In response to glucose and O, Sod1-derived HO 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.
铜/锌超氧化物歧化酶（Sod1）催化细胞毒性超氧自由基（O）歧化为氧气（O）和过氧化氢（HO），是一种关键的信号分子。在酿酒酵母中，我们之前发现 Sod1 参与了一个由 HO 介导的氧化还原信号回路，该回路将营养物质的可用性与能量代谢的控制联系起来。在葡萄糖和 O 的作用下，Sod1 衍生的 HO 稳定了一对保守的质膜激酶——酵母酪蛋白激酶 1 和 2（Yck1/2）——它们信号传递糖酵解生长和呼吸抑制。人类中的 Yck1/2 同源物，酪蛋白激酶 1-γ（CK1γ），是 Wingless 和 Int-1（Wnt）信号通路的一个组成部分，该通路对于调节早期发育和成人组织中的细胞命运和增殖至关重要，并且在许多癌症中失调。在此，我们通过发现 Sod1 在人胚肾 293（HEK293）细胞中调节 CK1γ 的表达，并发现 Sod1 在人胚肾 293（HEK293）细胞中调节 CK1γ 的表达，证明了 SOD1/YCK1 氧化还原信号轴在人类中的保守性，该通路对于经典 Wnt 信号和 Wnt 依赖性细胞增殖是必需的。
Zotero 插件