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A gene signal amplifier platform for monitoring the unfolded protein response.
Nature Chemical Biology ( IF 14.8 ) Pub Date : 2020-03-09 , DOI: 10.1038/s41589-020-0497-x
Carlos A Origel Marmolejo 1 , Bhagyashree Bachhav 2 , Sahiti D Patibandla 1 , Alexander L Yang 3 , Laura Segatori 1, 2, 4
Affiliation  

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.

中文翻译:

一个基因信号放大器平台,用于监测未折叠的蛋白质反应。

哺乳动物细胞中的基因表达是由多种调控机制指导的协调蛋白质驱动过程产生的,这些调控机制包括蛋白质-蛋白质相互作用,蛋白质定位,DNA修饰和染色质重排。基因表达的调控在应激反应途径中尤其重要。为了满足监控染色体基因表达以生成易于检测的信号输出以概括基因表达动力学的需求,我们开发了一种基因信号放大器平台,该平台将荧光输出的转录和翻译后调控与染色体靶基因的表达联系起来。我们生成了一个多重报告系统,用于监测未折叠蛋白反应的标记,复杂的信号转导途径,可响应内质网中的蛋白毒性应激而重塑基因表达。通过以高度灵敏的方式概述靶基因表达的转录和翻译控制机制,该平台提供了一种以优异的灵敏性和动态分辨率监测基因表达的技术。
更新日期:2020-04-24
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