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Inhibition of cell cycle progression in cells expressing HCV proteins

机译:表达HCV蛋白细胞细胞周期进展的抑制作用

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The expression of the structural proteins of HCV induces ER-stress response with a marked induction of GADD153. To assess the effect of GADD153 overexpression on cell cycle, we analyzed cell cycle profile in a tetracycline-regulated cell line expressing HCV proteins. In cultures in which the synthesis of HCV proteins was shut off (Tet 1000), the percentage of cells in the G0/G1, G2/M and S phases was 63.38, 15.1 and 21.52%, respectively. In contrast, in cultures fully induced (Tet 0), the percentage of cells in the S phase increased to 39,38%, while cells in the G0/G1 decreased to 43,61 %. Investigation of the mechanism revealed that GADD 153 up-regulation and accumulation of cells in S phase correlates with the activation of ER resident kinase PERK, glutathione depletion and modulation of bcl-2 family members.
机译:HCV的结构蛋白的表达诱导与GADD153的标记诱导的ER应激响应。为了评估GADD153过表达对细胞周期的影响,我们分析了表达HCV蛋白的四环素调节细胞系中的细胞周期曲线。在关闭HCV蛋白的合成的培养物中(TET 1000),G0 / G1,G2 / m和S相中细胞的百分比分别为63.38,15.1和21.52%。相反,在完全诱导的培养物(Tet 0)中,S相中细胞的百分比增加至39,38%,而G0 / G1中的细胞降低至43,61%。对机制的研究表明,GADD 153对S相的上调和积累的细胞与ER驻留激酶PERK,谷胱甘肽枯竭和BCL-2家族的调节相关。

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