Maintenance of the proteome (proteostasis) is essential for cellular homeostasis and prevents cytotoxic stress responses that arise from protein misfolding. However, little is known about how different types of misfolded proteins impact homeostasis, especially when protein degradation pathways are compromised. We examined the effects of misfolded protein expression on yeast growth by characterizing a suite of substrates possessing the same aggregation-prone domain but engaging different quality control pathways. We discovered that treatment with a proteasome inhibitor was more toxic in yeast expressing misfolded membrane proteins, and this growth defect was mirrored in yeast lacking a proteasome-specific transcription factor, Rpn4p. These results highlight weaknesses in the proteostasis network’s ability to handle the stress arising from an accumulation of misfolded membrane proteins.

中文翻译：

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不同类别的错误折叠蛋白对蛋白酶体功能受损的酵母的生长产生不同的影响

维持蛋白质组（蛋白质稳态）对于细胞稳态至关重要，并防止由蛋白质错误折叠引起的细胞毒性应激反应。然而，人们对不同类型的错误折叠蛋白质如何影响体内平衡知之甚少，尤其是当蛋白质降解途径受到损害时。我们通过表征一组具有相同易聚集结构域但参与不同质量控制途径的底物来检查错误折叠的蛋白质表达对酵母生长的影响。我们发现用蛋白酶体抑制剂处理在表达错误折叠膜蛋白的酵母中毒性更大，并且这种生长缺陷反映在缺乏蛋白酶体特异性转录因子 Rpn4p 的酵母中。