Bach Institute of Biochemistry, Federal Research Center "Fundamentals of Biotechnology" of the Russian Academy of Sciences, 119071 Moscow, Russia.
Int J Mol Sci. 2018 Nov 20;19(11):3663. doi: 10.3390/ijms19113663.
The [⁺] nonsense-suppressor determinant of is based on the formation of heritable amyloids of the Sup35 (eRF3) translation termination factor. [⁺] amyloids have variants differing in amyloid structure and in the strength of the suppressor phenotype. The appearance of [⁺], its propagation and manifestation depend primarily on chaperones. Besides chaperones, the Upf1/2/3, Siw14 and Arg82 proteins restrict [⁺] formation, while Sla2 can prevent [⁺] toxicity. Here, we identify two more non-chaperone proteins involved in [⁺] detoxification. We show that simultaneous lack of the Pub1 and Upf1 proteins is lethal to cells harboring [⁺] variants with a strong, but not with a weak, suppressor phenotype. This lethality is caused by excessive depletion of the Sup45 (eRF1) termination factor due to its sequestration into Sup35 polymers. We also show that Pub1 acts to restrict excessive Sup35 prion polymerization, while Upf1 interferes with Sup45 binding to Sup35 polymers. These data allow consideration of the Pub1 and Upf1 proteins as a novel [⁺] detoxification system.
[⁺]无意义抑制子决定簇存在于 Sup35（eRF3）翻译终止因子的可遗传淀粉样纤维中。[⁺]淀粉样纤维的结构变体和抑制表型强度存在差异。[⁺]的出现、传播和表现主要取决于伴侣蛋白。除伴侣蛋白外，Upf1/2/3、Siw14 和 Arg82 蛋白也限制[⁺]的形成，而 Sla2 可以防止[⁺]的毒性。在这里，我们确定了另外两种参与[⁺]解毒的非伴侣蛋白。我们发现，同时缺乏 Pub1 和 Upf1 蛋白会导致携带强抑制表型而非弱抑制表型[⁺]变体的细胞死亡。这种致死性是由于 Sup45（eRF1）终止因子被隔离到 Sup35 聚合物中，导致其过度耗尽所致。我们还表明，Pub1 可以限制 Sup35 朊病毒的过度聚合，而 Upf1 则干扰 Sup45 与 Sup35 聚合物的结合。这些数据表明，Pub1 和 Upf1 蛋白可以作为一种新的[⁺]解毒系统。
Zotero 插件
