Atg7调节p53的活性,以调节细胞周期和在代谢应激期间的生存
In Hye Lee1, Yoshichika Kawai, Maria M Fergusson
1Center for Molecular Medicine, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
Science (New York, N.Y.)
|April 14, 2012
概括
自基因Atg7在营养吸收过程中对细胞循环停止至关重要. 它调节p53,控制细胞分裂和细胞亡,防止DNA损伤和小鼠的致命性.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 缺少营养素会导致细胞循环停止,自和细胞死亡.
- 这些应激反应之间的相互作用尚未完全理解.
研究的目的:
- 研究自基因Atg7在细胞对营养缺乏的反应中的作用.
- 阐明Atg7,细胞循环调节和细胞死亡途径之间的关系.
主要方法:
- 使用了缺少Atg7.7的小鼠胚胎纤维细胞.
- 分析了细胞周期进展,p53结合,p21 ((CDKN1A) 转录,DNA损伤和细胞亡.
- 研究了Chk2删除对Atg7的生存效果.
主要成果:
- 缺少Atg7的细胞在饥饿时无法阻止细胞循环.
- Atg7直接与p53结合,调节p21 ((CDKN1A) 的表达,独立于它的酶活性.
- 在长时间的压力下,Atg7的缺失导致DNA损伤增加和p53依赖的亡.
- 抑制DNA损伤反应在Atg7的小鼠中部分挽救了致命性.
结论:
- 在营养缺乏引起的细胞循环停止时,Atg7是必不可少的.
- Atg7调节p53的活性,以控制细胞循环停止和细胞亡.
- 在管理细胞应激反应对营养限制方面,Atg7起着至关重要的作用.
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