p21激活酶4通过酸化NCoR1来抑制脂肪酸β-氧化和生成
Min Yan Shi1, Hwang Chan Yu1, Chang Yeob Han2
1Department of Biochemistry and Molecular Biology, Jeonbuk National University Medical School, Jeonju, 54896, Republic of Korea.
Nature communications
|August 17, 2023
概括
蛋白p21激活激酶4 (PAK4) 酸化NCoR1,抑制脂肪酸氧化和生成. 禁食时PAK4水平降低,这表明有调节肝脏脂肪代谢的途径.
科学领域:
- 代谢过程中的代谢.
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 核受体核心压缩剂1 (NCoR1) 对于调节脂肪酸代谢至关重要.
- 控制NCoR1活动的精确分子机制在很大程度上仍未被阐明.
研究的目的:
- 为了确定调节NCoR1.1.的激酶.
- 阐明p21激活激酶4 (PAK4) 在NCoR1-介导的脂肪酸代谢调节中的作用.
主要方法:
- 对NCoR1.1.的酸化部位进行映射.
- 在体内研究使用高脂肪饮食养的小鼠,NAFLD患者和肝细胞癌患者.
- 在小鼠中进行基因操纵 (过度表达,切除) 和药理抑制PAK4.
- 对PAK4蛋白质降解途径的分析.
主要成果:
- 在T1619/T2124处的PAK4酸化NCoR1,增强其核定位和PPARα相互作用.
- 过度表达PAK4会影响生成,并促进肝脏脂肪的积累.
- 禁食会降低PAK4水平,通过无处化和蛋白质体降解.
- 在高脂肪饮食模型,NAFLD和HCC中观察到高的PAK4和NCoR1酸化.
结论:
- 一个涉及PAK4,NCoR1和PPARα的新型信号通路调节脂肪酸氧化和生成.
- PAK4作为肝脂代谢的关键调节剂.
- 禁食通过调节的蛋白质降解来调节PAK4的活动.
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