AMPK通过在MTORC1-依赖和MTORC1-独立位点的脱化促进TFEB转录活性
Florentina Negoita1, Conchita Fraguas Bringas1, Kristina Hellberg1
1Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Autophagy
|February 9, 2026
概括
与此前的报道相反,AMP激活蛋白激酶 (AMPK) 激活在C端部位脱化转录因子EB (TFEB). 这种脱化对TFEB至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 转录因子EB (TFEB) 调节了溶酶体生物发生,自和能量恒温.
- 已知AMP激活蛋白激酶 (AMPK) 能够影响细胞能量状态.
研究的目的:
- 调查AMPK激活对TFEB酸化在C终端部位的影响.
- 澄清AMPK介导的TFEB酸化在转录激活中的作用.
主要方法:
- 使用合成TFEB的体外激酶测定.
- 用AMPK激活剂 (MK-8722),葡萄糖剥夺和mTOR抑制剂 (torin1) 进行细胞治疗.
- 西部斑点分析以检测TFEB酸化在N端和C端部位.
- 对TFEB目标基因表达的评估.
主要成果:
- AMPK激活导致TFEB在C端血清残留物 (S466,S467,S469) 的脱化.
- 在体外,TFEB C终端部位的合成是AMPK的不良基质.
- 在接受MK-8722,葡萄糖剥夺或torin1.1治疗时,N终端和C终端TFEB部位均被脱.
- 丧失AMPK功能取消了MK-8722诱导的脱化和TFEB基因诱导,但没有托林1诱导的效应.
结论:
- AMPK激活在C终端部位脱FEB,这与之前的发现相矛盾.
- 依赖AMPK的TFEB脱化对于诱导TFEB目标基因至关重要.
- 这些发现揭示了AMPK在细胞平衡中对TFEB的新型调节机制.
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