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The aggregation and inheritance of damaged proteins determines cell fate during mitosis

机译:受损蛋白的聚集和遗传决定了有丝分裂过程中的细胞命运

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摘要

Recent evidence suggests that proliferating cells polarize damaged proteins during mitosis to protect one cell from aging, and that the structural conformation of damaged proteins mediates their toxicity. We report that the growth, resistance to stress, and differentiation characteristics of a cancer cell line (PC12) with an inducible Huntingtin (Htt) fused to enhanced green fluorescent protein (GFP) are dependent on the conformation of Htt. Cell progeny containing inclusion bodies have a longer cell cycle and increased resistance to stress than those with diffuse Htt. Using live imaging, we demonstrate that asymmetric division resulting from a cell containing a single inclusion body produces sister cells with different fates. The cell that receives the inclusion body has decreased proliferation and increased differentiation compared with its sister cell without Htt. This is the first report that reveals a functional consequence of the asymmetric division of damaged proteins in mammalian cells, and we suggest that this is a result of inclusion body-induced proteasome impairment.
机译:最近的证据表明,增殖细胞在有丝分裂期间使受损的蛋白质极化,以保护一个细胞免于老化,受损蛋白质的结构构象介导了它们的毒性。我们报告说,与增强绿色荧光蛋白(GFP)融合的诱导型亨廷汀(Htt)癌细胞系(PC12)的生长,抗压力和分化特征取决于Htt的构象。与具有弥散性Htt的细胞相比,包含后代的细胞具有更长的细胞周期和更高的抗逆性。使用实时成像,我们证明了由包含单个包涵体的细胞引起的不对称分裂会产生具有不同命运的姊妹细胞。与没有Htt的姊妹细胞相比,接受包涵体的细胞增殖减少,分化增加。这是第一个揭示哺乳动物细胞中受损蛋白不对称分裂的功能性结果的报告,我们建议这是包涵体诱导的蛋白酶体损伤的结果。

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