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在营养应激和自中,AMPK对不同的Vps34复合物的差调节
Joungmok Kim1, Young Chul Kim, Chong Fang
1Department of Oral Biochemistry and Molecular Biology, Research Center for Tooth and Periodontal Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul 130-701, Korea.
Cell
|January 22, 2013
概括
在营养压力期间,AMP激活蛋白激酶 (AMPK) 不同调节Vps34复合体. AMPK抑制非自Vps34,同时激活亲自复合体,控制细胞存活和自诱导.
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 生化学
背景情况:
- 自是一种细胞应激反应,在营养饥饿期间对生存至关重要.
- 第三类酸丁醇-3激酶,Vps34,是囊泡贩运和自诱导的核心,存在于多个蛋白质复合体中.
- AMP激活蛋白激酶 (AMPK) 是一个关键的细胞能量传感器,参与了代谢调节.
研究的目的:
- 阐明AMPK在调节不同Vps34复合物的作用.
- 了解AMPK如何调节Vps34活动,以应对营养压力.
- 研究AMPK,Vps34复合体和自诱导之间的相互作用.
主要方法:
- 对Vps34和Beclin1.1的酸化位点分析.
- 研究Vps34复合物的形成和活动.
- 在葡萄糖饥饿条件下进行细胞响应测定.
主要成果:
- AMPK在T163/S165酸化Vps34,抑制非自性Vps34活性和PI(3) P产生,从而在饥饿期间保护细胞.
- 在S91/S94的位置上,AMPK可化Beclin1,激活亲自 Vps34复合体,并诱导自.
- 作为亲自复合体的组成部分Atg14L,可以选择性地增强AMPK的Beclin1酸化,同时抑制Vps34酸化,从而指导AMPK的调节作用.
结论:
- 在营养压力期间,AMPK在调节Vps34复合体方面发挥着关键的双重作用.
- 通过AMPK对Vps34和Beclin1的差异酸化决定了细胞在生存和自之间的命运.
- Atg14L是AMPK对Vps34复合物的特定激活或抑制的关键决定因素,揭示了一个复杂的调节网络.
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