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

Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway.
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Cu/Zn超氧化物歧化酶(SOD 1)调节经典Wnt信号通路。

DOI:
10.1016/j.bbrc.2020.11.011
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发表时间:
2021-01-01
影响因子:
3.1
通讯作者:
Reddi AR
Reddi AR
中科院分区:
生物学4区
文献类型:
--
作者:
Chandrasekharan B;Montllor-Albalate C;Colin AE;Andersen JL;Jang YC;Reddi AR

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Cu/Zn超氧化物歧化酶(Sod 1)催化细胞毒性超氧自由基(O2·−)转化为氧气(O2)和过氧化氢(H2 O2),这是一种关键的信号分子。在酿酒酵母中,我们之前发现Sod 1参与H2 O2介导的氧化还原信号通路,该通路将营养物质的利用与能量代谢的控制联系起来。响应葡萄糖和O2,Sod 1衍生的H2 O2稳定了一对保守的质膜激酶-酵母酪蛋白激酶1和2(Yck 1/2)-这信号糖酵解生长和呼吸抑制。人类Yck 1/2同源物酪蛋白激酶1-γ(CK 1 γ)是Wingless和Int-1(Wnt)信号通路的组成部分,其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SOD 1调节人胚肾293(HEK 293)细胞中CK 1 γ的表达,并且是经典Wnt信号传导和Wnt依赖性细胞增殖所必需的,建立了SOD 1/YCK 1氧化还原信号传导轴在人类中的保守性。
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.
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