瘤抑制剂LATS1的O-GlcNAcylation通过PLK1驱动了线粒细胞的进展
Li Meng1, Yunfeng Wang2, Wen Zhou3
1Beijing Key Laboratory of DNA Damage Response and College of Life Sciences, Capital Normal University, Beijing, China.
The Journal of biological chemistry
|December 3, 2025
概括
六胺生物合成途径通过修改LATS1蛋白稳定性来调节Hippo途径. 这种O-GlcNAcylation影响细胞增殖和器官大小,将葡萄糖水平与组织生长联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生化学
- 发展生物学 发展生物学
背景情况:
- 河马通路对于组织生长和器官平衡至关重要,由内在和外在信号调节.
- 大型瘤抑制剂1和2 (LATS1/2) 是Hippo通路中的关键激酶.
- LATS1通过酸化MYPT1来调节线性进展,从而抵消波罗样酶1 (PLK1).
研究的目的:
- 为了研究赫克索胺生物合成途径在调节河马途径中的作用.
- 阐明O-GlcNAcylation影响LATS1功能和下游信号的机制.
- 确定LATS1 O-GlcNAcylation对细胞增殖和器官大小的影响.
主要方法:
- 在LATS1和O-GlcNAc转移酶 (OGT) 之间的相互作用研究.
- 质谱测量用于在LATS1.1.上绘制O-GlcNAcylation位点的地图.
- 对LATS1蛋白稳定性,MYPT1酸化和PLK1活性进行分析.
- 在Drosophila体内进行体内研究,以评估翅膀尺寸调节.
主要成果:
- LATS1与OGT直接相互作用,并在特定的血清素和三素残留物 (S479/S482/T484/T485) 上经过O-GlcNAcylation.
- O-GlcNAcylation 降低了 LATS1 蛋白质的稳定性,并降低了其下游基质 MYPT1.1. 的酸化.
- 这导致PLK1的酸化增加,促进了线粒细胞的进展.
- LATS1的O-GlcNAcylation促进了Drosophila的翅膀大小.
结论:
- 六胺生物合成途径通过LATS1.1.的O-GlcNAcylation调节Hippo途径.
- LATS1的O-GlcNAcylation影响了蛋白质的稳定性,下游信号传递和线粒细胞的进展.
- 这项研究揭示了葡萄糖代谢,LATS1和细胞增殖和器官大小调节之间的联系.
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