基础医学与临床 ›› 2018, Vol. 38 ›› Issue (1): 98-102.

• 短篇综述 • 上一篇    下一篇

Sestrin功能的分子机制研究进展

胡茜,韩薇   

  1. 哈尔滨医科大学附属一院
  • 收稿日期:2016-11-28 修回日期:2017-01-17 出版日期:2018-01-05 发布日期:2017-12-26
  • 通讯作者: 韩薇 E-mail:hanwei2@medmailcom.cn
  • 基金资助:
    国家自然科学基金

Advances in molecular mechanism of Sestrin function

  • Received:2016-11-28 Revised:2017-01-17 Online:2018-01-05 Published:2017-12-26

摘要: 活性氧(ROS)的过度堆积和雷帕霉素作用靶点复合物1(mTORC1)的持续活化是导致相关疾病发生的主要原因。Sestrin是一种抗衰老的多功能蛋白,它作为过氧化物还原酶或者过氧化物酶减少ROS,Sestrin上调自嗜及促进Nrf2活化抑制ROS。Sestrin结合GATOR2,一方面释放GATOR1,抑制RagA/B活性。另一方面启动AMPK,使结节硬化复合物2(TSC2)磷酸化,抑制 Rheb活性。通过抑制RagA/B和Rheb抑制mTORC1。亮氨酸浓度可改变Sestrin构像进而改变其调控mTORC1的功能。

关键词: Sestrin, 活性氧, 雷帕霉素作用靶点复合物1, 亮氨酸

Abstract: Excessive accumulation of reactive oxygen species (ROS) and Chronic activation of mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) result associated pathologies.Sestrin is a versatile anti-aging protein.Sestrin as a Prx Reductase or as a Peroxidase,which reduce ROS.Sestrin can upregulate autophagy and upregulate Nrf2 and its antioxidant targets,which inhibit ROS. Sestrin bind to GATOR2, On the one hand liberating GATOR1, and thereby promote the RagA/B-inhibiting activity.On the another hand activating AMPK which promote phosphorylation of TSC2,and thereby inhibit Rheb.Sestrin inhibit mTORC1 through its inhibition of RagA/B and Rheb.Concentration of leucine can change conformation of Sestrin,and thereby change its regulation of mTORC1.

Key words: Sestrin, ROS, mTORC1, leucine

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