通过NEDD4L介导的Gasdermin D和E泛化调节细胞死亡和组织损伤
Sonia S Shah1,2, Jantina A Manning3,4, Yoon Lim3,4
1Centre for Cancer Biology, University of South Australia, Adelaide, SA, 5001, Australia. sonia.shah@unisa.edu.au.
Cell death and differentiation
|November 19, 2025
概括
无素酶NEDD4L控制了气体皮质蛋白 (GSDM) 的水平,这对细胞死亡途径 (如热和亡) 至关重要. 缺少NEDD4L导致GSDM积累,导致组织损伤和增加对细胞死亡的敏感性.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 加斯德明 (GSDM) 蛋白质是热和灭的关键媒介.
- GSDMD和GSDME特别准线粒体膜,导致细胞死亡.
- 调节GSDM蛋白稳定性对于控制细胞死亡途径至关重要.
研究的目的:
- 确定GSDMD和GSDME的关键监管机构.
- 为了研究在GSDM调控中泛素酶NEDD4L的作用.
- 阐明NEDD4L对GSDM介导的细胞死亡和组织稳态的影响.
主要方法:
- 化试验评估NEDD4L对GSDM的影响.
- 生成和分析Nedd4l淘汰赛小鼠模型 (全球和组织特定).
- 细胞测定测量GSDM激活,IL-1β释放,以及对细胞死亡刺激的敏感性.
主要成果:
- NEDD4L直接无处不在GSDMD和GSDME,控制它们的稳定性和表达.
- 由于高GSDM,Nedd4l淘汰赛小鼠表现出产前死亡率,肺部和脏受损.
- 细胞中的NEDD4L缺乏会增加GSDM激活,IL-1β释放,以及对各种细胞死亡触发物的敏感性.
结论:
- NEDD4L是GSDMD和GSDME的关键负调节剂.
- NEDD4L防止了GSDM的积累,从而保护组织免受过度的细胞死亡.
- 这项研究揭示了一种新的机制,将乌比奎丁酶活性与GSDM稳定性和细胞死亡调节联系起来.
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