Sestrin功能的分子机制研究进展

Advances in molecular mechanism of Sestrin function

活性氧(ROS)的过度堆积和雷帕霉素作用靶点复合物1(m TORC1)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Rag A/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Rag A/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。

Excessive accumulation of reactive oxygen species（ ROS） and Chronic activation of mechanistic target of rapamycin（ mTOR） complex 1（ mTORC1） is 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,releasing GATOR1,and thereby promote the Rag A/B-inhibiting activity. On the another hand activating AMPK which promote phosphorylation of TSC2,and thereby inhibit Rheb.Sestrin inhibit m TORC1 through its inhibition of Rag A/B and Rheb. Concentration of leucine can change conformation of Sestrin,and thereby change its regulation of m TORC1.