Prion variant maintained only at high levels of the Hsp104 disaggregase
Prion variant maintained only at high levels of the Hsp104 disaggregase
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DOI：
10.1007/s00294-005-0035-0
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发表时间：
2006-01-01
期刊：
影响因子：
2.5
通讯作者：
Chernoff, YO
中科院分区：
文献类型：
--
作者：
Borchsenius, AS;Müller, S;Chernoff, YO
酵母朊病毒 [PSI+] 是翻译终止因子 Sup35 的自我永存聚合亚型。 [PSI+] 传播受到中等水平的促进，并被高水平的伴侣 Hsp104 拮抗。与假定过量的 Hsp104 通过分解朊病毒聚合物作用于 [PSI+] 的模型一致，我们表明 Sup35 水平的增加，伴随着朊病毒聚集体大小的增加，也部分保护了 [PSI+] 免于被过量的 Hsp104 消除。尽管保留了 [PSI+]，但过量的 Hsp104 会降低 [PSI+] 菌株中过量产生的 Sup35 的毒性。 [PSI+] 的遗传性变体已被分离出来，并且仅在 Hsp104 水平增加的情况下才能维持，其特征是聚集体尺寸异常大，并且对 Hsp70 伴侣 Ssa1 的过量产生表现出改变的反应。这些特征类似于之前描述的由 Sup35 的缺失衍生物产生的朊病毒，但与任何序列改变无关，并且仅在蛋白质水平上受到控制。我们的数据证明存在条件稳定的朊病毒变体，仅在改变的热休克蛋白水平下维持，原则上，如果朊病毒蛋白的正常细胞功能在这种条件下对细胞有害，那么这可能是有益的。
The yeast prion [PSI+] is a self-perpetuating aggregated isoform of the translation termination factor Sup35. [PSI+] propagation is promoted by moderate levels and antagonized by high levels of the chaperone Hsp104. In agreement with the model postulating that excess Hsp104 acts on [PSI+] by disaggregating prion polymers, we show that an increase in Sup35 levels, accompanied by an increase in size of prion aggregates, also partially protects [PSI+] from elimination by excess Hsp104. Despite retention of [PSI+], excess Hsp104 decreases toxicity of overproduced Sup35 in [PSI+] strains. A heritable variant of [PSI+], which has been isolated and is maintained only in the presence of increased levels of Hsp104, is characterized by an abnormally large aggregate size, and exhibits an altered response to overproduction of the Hsp70 chaperone Ssa1. These features resemble the previously described prion generated by a deletion derivative of Sup35, but are not associated with any sequence alteration and are controlled exclusively at the protein level. Our data provide a proof of the existence of conditionally stable prion variants maintained only at altered levels of Hsps, that could in principle be beneficial if the normal cellular function of a prion protein becomes detrimental to the cell in such conditions.