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首页> 外文期刊>Molecular and Cellular Biology >skn-1-Dependent and -Independent Regulation of aip-1 Expression following Metabolic Stress in Caenorhabditis elegans
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skn-1-Dependent and -Independent Regulation of aip-1 Expression following Metabolic Stress in Caenorhabditis elegans

机译：秀丽隐杆线虫代谢应激后aip-1表达的skn-1依赖性和非依赖性调节

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Maintenance of a stable, properly folded, and catalytically active proteome is a major challenge to organisms in the face of multiple internal and external stresses which damage proteins and lead to protein misfolding. Here we show that internal metabolic stress produced by reactive intermediates resulting from tyrosine degradation triggers the expression of the aip-1 gene, which is critical in responses to the environmental toxin arsenic and the clearance of unstable polyglutamine and Aβ proteins. aip-1 acts via binding to the proteosome and enhancing proteosomal function. We find that full induction of aip-1 depends on the oxidative-stress-responsive skn-1 transcription factor but significant induction still occurs without skn-1. Importantly, activation of skn-1 with wdr-23(RNAi), which dramatically induces the expression of other skn-1 target genes, produces a minimal increase in aip-1 expression. This suggests that the previously demonstrated specificity in aip-1/AIRAP induction could reflect the actions of multiple synergistic activators, such as the heat shock factor homolog hsf-1, which we also find is required for full induction. These may be triggered by proteosome dysfunction, as we find that this event links the multiple inducers of aip-1. Together, our results show that cell stress triggers aip-1 expression by both skn-1-dependent and -independent pathways.
机译：面对多种内部和外部应力（破坏蛋白质并导致蛋白质错误折叠），维持稳定，正确折叠且具有催化活性的蛋白质组是有机体面临的主要挑战。在这里，我们表明酪氨酸降解引起的反应性中间体产生的内部代谢应激会触发 aip - 1 基因的表达，这对环境毒素砷和砷的反应至关重要。清除不稳定的聚谷氨酰胺和Aβ蛋白。 aip - 1 通过结合蛋白体和增强蛋白体功能发挥作用。我们发现 aip - 1 的完全诱导取决于氧化应激反应 skn - 1 转录因子但是在没有 skn - 1 的情况下仍然会发生明显的归纳。重要的是，使用 wdr - 23 （ RNAi ）激活 skn - 1 ，显着诱导其他 skn - 1 靶基因的表达，产生最小的 aip - 1 表达增加。这表明先前证明的在 aip - 1 / AIRAP诱导中的特异性可能反映了多种协同激活剂的作用，例如热休克因子同源物 hsf - 1 ，我们也发现它是完全归纳所必需的。这些可能是由于蛋白体功能障碍引起的，因为我们发现该事件与 aip - 1 的多种诱导物有关。在一起，我们的结果表明，细胞应激通过 skn - 1 依赖性和-触发 aip - 1 表达。独立途径。

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