The core protein of hepatitis C virus is imported into the nucleus by transport receptor Kap123p but inhibits Kap121p-dependent nuclear import of yeast AP1-like transcription factor in yeast cells
The core protein of hepatitis C virus is imported into the nucleus by transport receptor Kap123p but inhibits Kap121p-dependent nuclear import of yeast AP1-like transcription factor in yeast cells
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DOI：
10.1074/jbc.m203939200
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发表时间：
2002-10-18
影响因子：
4.8
通讯作者：
Nomoto, A
中科院分区：
文献类型：
--
作者：
Isoyama, T;Kuge, S;Nomoto, A
丙型肝炎病毒（HCV）的核心蛋白是病毒核衣壳的主要成分。HCV核心蛋白包括核定位信号样序列，并且对细胞代谢具有各种影响，例如在转录、凋亡和转化的调节中发挥作用。为了研究核心蛋白对核质转运的影响的可能性，我们使用酵母酿酒酵母作为模型系统。核心蛋白（p23）被加工成p21，并定位在酵母细胞的细胞质和细胞核中，类似于在哺乳动物细胞中观察到的几种情况。核心蛋白的核输入需要小GTdR an/Gsp 1 p的活性，并且在酵母细胞中由Kap 123 p介导。当核心蛋白在酵母细胞中表达时，酵母AP 1样转录因子Yap 1 p进入细胞核的输入被抑制。涉及Kap 121 p（也称为Pse 1 p，一种Yap 1 p核输入受体）的体外实验表明，在核心蛋白存在下，与Kap 121 p结合的Yap 1 p的量减少。这些结果表明，HCV核心蛋白通过干扰蛋白质向细胞核的转运来影响细胞代谢。
The core protein of hepatitis C virus (HCV) is a major component of the viral nucleocapsid. The HCV core protein includes nuclear localization signal-like sequences and has various effects on cellular metabolism, playing roles, for example, in the regulation of transcription, apoptosis, and transformation. To examine the possibility of an effect of the core protein on nucleocytoplasmic transport, we used the yeast Saccharomyces cerevisiae as a model system. The core protein (p23) is processed to p21 and is localized in both the cytoplasm and nucleus in yeast cells, similar to that observed in mammalian cells in several cases. The nuclear import of the core protein requires the activity of small GTPase Ran/Gsp1p and is mediated by Kap123p in yeast cells. When the core protein was expressed in yeast cells, the import of the yeast AP1-like transcription factor Yap1p into the nucleus was inhibited. Experiments in vitro involving Kap121p, also known as Pse1p, a receptor for the nuclear import of Yap1p, indicated that the amount of Yap1p bound to Kap121p was reduced in the presence of core protein. These results suggest that the HCV core protein affects cellular metabolism by disturbing transport of proteins to the nucleus.