PDF(Pubmed)
Abstract：
The Integrated Stress Response (ISR) is an essential homeostatic signaling network that controls the cell\'s biosynthetic capacity. Four ISR sensor kinases detect multiple stressors and relay this information to downstream effectors by phosphorylating a common node: the alpha subunit of the eukaryotic initiation factor eIF2. As a result, general protein synthesis is repressed while select transcripts are preferentially translated, thus remodeling the proteome and transcriptome. Mounting evidence supports a view of the ISR as a dynamic signaling network with multiple modulators and feedback regulatory features that vary across cell and tissue types. Here, we discuss updated views on ISR sensor kinase mechanisms, how the subcellular localization of ISR components impacts signaling, and highlight ISR signaling differences across cells and tissues. Finally, we consider crosstalk between the ISR and other signaling pathways as a determinant of cell health.
摘要：
综合应激反应(ISR)是控制细胞生物合成能力的基本稳态信号网络。四种ISR传感器激酶检测多种应激源，并通过磷酸化一个共同的节点：真核起始因子eIF2的α亚基将此信息传递给下游效应子。因此,一般的蛋白质合成被抑制，而选择的转录本被优先翻译，从而重塑蛋白质组和转录组。安装证据支持将ISR视为具有多个调制器和反馈调节特征的动态信令网络，这些特征在细胞和组织类型之间有所不同。这里,我们讨论了ISR传感器激酶机制的最新观点，ISR组件的亚细胞定位如何影响信令，并强调跨细胞和组织的ISR信号传导差异。最后,我们认为ISR和其他信号通路之间的串扰是细胞健康的决定因素.
