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保守的热应激转录因子(又叫热休克转录因子)HSF-1在细胞抗应激和寿命决定中发挥关键作用。HSF-1的经典功能是调节细胞伴侣基因的编码网络,保护蛋白免受外部环境应激因素和内部与年龄相关的损害。利用秀丽隐杆线虫为实验对象,我们制作修饰的HSF-1株在不诱导伴侣蛋白表达情况下,增强了抗应激能力,延长了线虫的寿命。这种健康效应通过调节钙结合蛋白PAT-10实现。缺失PAT-10导致肌动蛋白细胞骨架受损,抗应激能力下降和寿命缩短。过表达PAT-10蛋白则使肌动蛋白纤维稳定性和抗应激能力增强,寿命延长。该结果表明在应激和衰老等状况下,HSF-1除了调节细胞伴侣蛋白外,在维持细胞骨架完整性和细胞功能方面发挥了突出作用。
原文链接:http://www.sciencemag.org/content/346/6207/360.full
文题:HSF-1–mediated cytoskeletal integrity determines thermotolerance and life span
摘要:The conserved heat shock transcription factor–1 (HSF-1) is essential to cellular stress resistance and life-span determination. The canonical function of HSF-1 is to regulate a network of genes encoding molecular chaperones that protect proteins from damage caused by extrinsic environmental stress or intrinsic age-related deterioration. In Caenorhabditis elegans, we engineered a modified HSF-1 strain that increased stress resistance and longevity without enhanced chaperone induction. This health assurance acted through the regulation of the calcium-binding protein PAT-10. Loss of pat-10 caused a collapse of the actin cytoskeleton, stress resistance, and life span. Furthermore, overexpression of pat-10 increased actin filament stability, thermotolerance, and longevity, indicating that in addition to chaperone regulation, HSF-1 has a prominent role in cytoskeletal integrity, ensuring cellular function during stress and aging.
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