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TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans

机译:TRX-1在秀丽隐杆线虫中非自主地调节SKN-1核定位细胞。

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摘要

The Caenorhabditis elegans oxidative stress response transcription factor, , is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by , to the expansive list of regulators. We report that loss of promotes nuclear localization of intestinal in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, and , do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while regulates nuclear localization, classical transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism.
机译:秀丽隐杆线虫氧化应激反应转录因子,对于维持氧化还原稳态是必需的,并且是Nrf家族转录因子的功能直系同源物。控制这些转录因子的多种调节水平突显了它们的重要性。在这里,我们将由编码的硫氧还蛋白添加到大量的调节剂中。我们报告说,从ASJ神经元的氧化还原独立,细胞非自主方式促进肠核定位的损失。此外,该调节对于硫氧还蛋白家族而言并不通用,因为另外两个秀丽隐杆线虫硫氧还蛋白在该过程中不起作用。此外,依赖TRX-1的调节需要来自p38 MAPK信号通路的信号。然而,虽然调节核定位,但与应激反应有关的经典转录活性在很大程度上不受影响。有趣的是,RNA-Seq分析显示,丢失基因会引起全基因范围的几类基因的下调。编码胶原蛋白和脂质转运的那些最为普遍。在一起,这些结果揭示了硫氧还蛋白在以非自主方式调节肠核定位中的新作用,从而有助于了解整个生物体内维持氧化还原稳态的过程。

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