整合应激反应的终止机制

Full article and list of author affiliations: https://doi.org/10.1126/ science.adw5137 Claudia De Miguel†, Sigurdur R. Thorkelsson†, Agnieszka Fatalska‡, George Hodgson‡, Maximillian Dalglish, Chao Wang, Anne Bertolotti* INTRODUCTION: Survival depends on the ability to detect, respond to, and recover from internal and external challenges. Stress signaling pathways evolved to provide cells with defense mecha- nisms that maintain cellular homeostasis under adverse condi- tions. In mammals, four kinases—HRI, PKR, GCN2, and PERK—are activated by a range of different stimuli to phosphory- late eukaryotic translation initiation factor eIF2 on Ser52 of its α subunit and initiate the integrated stress response (ISR). P-eIF2 binds and inhibits its essential recycling factor eIF2B, thereby slowing down translation. …