Aneuploidy causes proteotoxic stress in yeast
Aneuploidy causes proteotoxic stress in yeast
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DOI：
10.1101/gad.207407.112
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发表时间：
2012-12-15
影响因子：
10.5
通讯作者：
Amon, Angelika
中科院分区：
文献类型：
--
作者：
Oromendia, Ana B.;Dodgson, Stacie E.;Amon, Angelika
整个染色体的获得或丢失导致非整倍体，迄今为止分析的所有真核生物对这种情况的耐受性都很差。非整倍体如何影响机体和细胞生理尚不清楚。我们发现非整倍体芽殖酵母细胞处于蛋白毒性胁迫下。非整倍体菌株容易聚集内源性蛋白质以及异位表达的难以折叠的蛋白质，如含有聚谷氨酰胺（polyQ）延伸的蛋白质。非整倍体酵母菌株中蛋白质聚集的形成可能是由于蛋白质质量控制系统的限制，因为蛋白酶体和至少一个伴侣蛋白家族Hsp90在许多非整倍体菌株中受到损害。非整倍体与蛋白质聚集体的形成和持续之间的联系可能对癌症和神经变性等疾病具有重要意义。
Gains or losses of entire chromosomes lead to aneuploidy, a condition tolerated poorly in all eukaryotes analyzed to date. How aneuploidy affects organismal and cellular physiology is poorly understood. We found that aneuploid budding yeast cells are under proteotoxic stress. Aneuploid strains are prone to aggregation of endogenous proteins as well as of ectopically expressed hard-to-fold proteins such as those containing polyglutamine (polyQ) stretches. Protein aggregate formation in aneuploid yeast strains is likely due to limiting protein quality-control systems, since the proteasome and at least one chaperone family, Hsp90, are compromised in many aneuploid strains. The link between aneuploidy and the formation and persistence of protein aggregates could have important implications for diseases such as cancer and neurodegeneration.