Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
FEBS Lett. 2012 Jul 30;586(16):2318-25. doi: 10.1016/j.febslet.2012.05.023. Epub 2012 May 31.
Hepatitis C virus core protein (Core) contributes to HCV pathogenicity. Here, we demonstrate that Core impairs growth in budding yeast. We identify HSP90 inhibitors as compounds that reduce intracellular Core protein level and restore yeast growth. Our results suggest that HSC90 (Hsc82) may function in the protection of the nascent Core polypeptide against degradation in yeast and the C-terminal region of Core corresponding to the organelle-interaction domain was responsible for Hsc82-dependent stability. The yeast system may be utilized to select compounds that can direct the C-terminal region to reduce the stability of Core protein.
丙型肝炎病毒核心蛋白(Core)有助于 HCV 的发病机制。在这里,我们证明 Core 会损害出芽酵母的生长。我们发现 HSP90 抑制剂是降低细胞内 Core 蛋白水平并恢复酵母生长的化合物。我们的结果表明,HSC90(Hsc82)可能在保护新生 Core 多肽免受酵母降解中起作用,并且 Core 的 C 末端区域对应于细胞器相互作用域,负责 Hsc82 依赖性稳定性。酵母系统可用于选择可将 C 末端区域定向以降低 Core 蛋白稳定性的化合物。