A gene signal amplifier platform for monitoring the unfolded protein response.
A gene signal amplifier platform for monitoring the unfolded protein response.
复制标题
用于监测未折叠蛋白质反应的基因信号放大器平台。
DOI：
10.1038/s41589-020-0497-x
复制
发表时间：
2020
影响因子：
14.8
通讯作者：
Segatori,Laura
中科院分区：
文献类型：
--
作者：
OrigelMarmolejo,CarlosA;Bachhav,Bhagyashree;Patibandla,SahitiD;Yang,AlexanderL;Segatori,Laura
哺乳动物细胞中的基因表达是由不同调节机制引导的协调蛋白质驱动过程引起的，包括蛋白质-蛋白质相互作用、蛋白质定位、DNA修饰和染色质重排。基因表达调控在应激反应途径中尤为重要。为了满足监测染色体基因表达的需要，产生重现基因表达动态的容易检测的信号输出，我们开发了一种基因信号放大器平台，其将荧光输出的转录和翻译后调节与染色体靶基因的表达联系起来。我们产生了一个多重报告系统，用于监测未折叠蛋白反应的标志物，这是一种复杂的信号转导途径，可重塑内质网中蛋白毒性应激的基因表达。通过以高灵敏度再现靶基因表达的转录和翻译控制机制，该平台提供了一种以上级灵敏度和动态分辨率监测基因表达的技术。
Gene expression in mammalian cells results from coordinated protein-driven processes guided by diverse mechanisms of regulation, including protein–protein interactions, protein localization, DNA modifications and chromatin rearrangement. Regulation of gene expression is particularly important in stress-response pathways. To address the need to monitor chromosomal gene expression generating a readily detectable signal output that recapitulates gene expression dynamics, we developed a gene signal amplifier platform that links transcriptional and post-translational regulation of a fluorescent output to the expression of a chromosomal target gene. We generated a multiplex reporter system for monitoring markers of the unfolded protein response, a complex signal transduction pathway that remodels gene expression in response to proteotoxic stress in the endoplasmic reticulum. By recapitulating the transcriptional and translational control mechanisms underlying the expression of a target gene with high sensitivity, this platform provides a technology for monitoring gene expression with superior sensitivity and dynamic resolution.