In response to diverse stress stimuli, eukaryotic cells activate a common adaptive pathway, termed the integrated stress response (ISR), to restore cellular homeostasis. The core event in this pathway is the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) by one of four members of the eIF2α kinase family, which leads to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, that together promote cellular recovery. The gene expression program activated by the ISR optimizes the cellular response to stress and is dependent on the cellular context, as well as on the nature and intensity of the stress stimuli. Although the ISR is primarily a pro-survival, homeostatic program, exposure to severe stress can drive signaling toward cell death. Here, we review current understanding of the ISR signaling and how it regulates cell fate under diverse types of stress.

中文翻译：

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综合应激反应。

为了响应不同的压力刺激，真核细胞激活一种共同的适应性途径，称为综合压力反应 (ISR)，以恢复细胞稳态。该途径的核心事件是真核翻译起始因子 2 α (eIF2α) 被 eIF2α 激酶家族的四个成员之一磷酸化，这导致整体蛋白质合成减少和选定基因的诱导，包括转录因子ATF4，共同促进细胞恢复。ISR 激活的基因表达程序优化了细胞对压力的反应，并且取决于细胞环境以及压力刺激的性质和强度。尽管 ISR 主要是一种促进生存的稳态程序，但暴露于严重压力下会驱动信号传导至细胞死亡。这里，