Barbitoff Yury A, Matveenko Andrew G, Moskalenko Svetlana E, Zemlyanko Olga M, Newnam Gary P, Patel Ayesha, Chernova Tatiana A, Chernoff Yury O, Zhouravleva Galina A
Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034, Russia.
Laboratory of Amyloid Biology, St. Petersburg State University, St. Petersburg 199034, Russia.
Mol Microbiol. 2017 Jul;105(2):242-257. doi: 10.1111/mmi.13697. Epub 2017 May 9.
Yeast self-perpetuating protein aggregates (prions) provide a convenient model for studying various components of the cellular protein quality control system. Molecular chaperones and chaperone-sorting factors, such as yeast Cur1 protein, play key role in proteostasis via tight control of partitioning and recycling of misfolded proteins. In this study, we show that, despite the previously described ability of Cur1 to antagonize the yeast prion [URE3], it enhances propagation and phenotypic manifestation of another prion, [PSI ]. We demonstrate that both curing of [URE3] and enhancement of [PSI ] in the presence of excess Cur1 are counteracted by the cochaperone Hsp40-Sis1 in a dosage-dependent manner, and show that the effect of Cur1 on prions parallels effects of the attachment of nuclear localization signal to Sis1, indicating that Cur1 acts on prions via its previously reported ability to relocalize Sis1 from the cytoplasm to nucleus. This shows that the direction in which Cur1 influences a prion depends on how this specific prion responds to relocalization of Sis1.
酵母自我延续性蛋白质聚集体（朊病毒）为研究细胞蛋白质质量控制系统的各种组成部分提供了一个便利的模型。分子伴侣和伴侣分选因子，如酵母Cur1蛋白，通过严格控制错误折叠蛋白的分配和循环利用，在蛋白质稳态中发挥关键作用。在本研究中，我们发现，尽管之前描述过Cur1具有拮抗酵母朊病毒[URE3]的能力，但它却增强了另一种朊病毒[PSI+]的传播和表型表现。我们证明，在过量Cur1存在的情况下，[URE3]的消除和[PSI+]的增强都被共伴侣Hsp40-Sis1以剂量依赖的方式抵消，并且表明Cur1对朊病毒的作用与将核定位信号附加到Sis1上的作用相似，这表明Cur1通过其先前报道的将Sis1从细胞质重新定位到细胞核的能力作用于朊病毒。这表明Cur1影响朊病毒的方向取决于这种特定朊病毒对Sis1重新定位的反应方式。
