通过AMPK介导的酸化在瘤细胞中调节D介导的气体灭
Xiufeng Chu1,2, Xiang Xiao1, Guangchuan Wang1
1Immunobiology and Transplant Science Center, Houston Methodist Hospital, Texas Medical Center, Houston, TX, USA.
由AMP激活的蛋白激酶 (AMPK) 抑制了气体皮质D.
科学领域:
- 细胞生物学 细胞生物学
- 细胞死亡的分子机制
- 癌症研究 癌症研究
背景情况:
- 加斯德明D (GSDMD) 通过其N-终端域启动激素灭亡,即被编程的细胞死亡.
- GSDMD的毛孔形成活动受到自身抑制机制的严格调节.
- 在释放后,GSDMD N-终端域 (GD-NT) 的调节仍然基本未知.
研究的目的:
- 研究控制GD-NT.细胞分解活性的调节机制.
- 探索AMP激活蛋白激酶 (AMPK) 在GD-NT功能中的作用.
- 阐明AMPK对瘤细胞中GSDMD介导的热的影响.
主要方法:
- 开发一种TetOn系统,用于诱导瘤细胞中的GD-NT表达.
- 生物化学测试以评估GD-NT的寡合化和毛孔形成能力.
- 在体内瘤模型评估抗瘤活性和瘤生长.
主要成果:
- AMPK激活会负面调节GD-NT细胞分解活性.
- 在血清46 (pS46-GD) 处AMPK酸化GD-NT,抑制其寡合化和孔隙形成.
- 通过AMPK介导的酸化消除了GD-NT的抗瘤作用,在体内促进了瘤的侵袭性生长.
结论:
- AMPK在消极调节 GSDMD N-终端域的细胞分解活性方面发挥着至关重要的作用.
- 通过AMPK介导的GSDMD的酸化是一种控制热的新机制.
- 这项研究揭示了AMPK信号通路与癌细胞中GSDMD介导的烧灭细胞之间的意想不到的联系.
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