Hepatitis C virus core protein interacts with 14-3-3 protein and activates the kinase Raf-1

Hepatitis C virus core protein interacts with 14-3-3 protein and activates the kinase Raf-1
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DOI:
10.1128/jvi.74.4.1736-1741.2000
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发表时间:
2000-02-01
影响因子:
5.4
通讯作者:
Hino, O
Hino, O
中科院分区:
医学2区
文献类型:
--
作者:
Aoki, H;Hayashi, J;Hino, O

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持续性丙型肝炎病毒(HCV)感染是人类慢性肝功能障碍的主要原因,其流行病学蛋白已被报道与体外和体内细胞生长调节有关,尽管解释这些影响的机制尚不清楚。在本研究中,我们发现14-3-3蛋白家族成员与HCV核心蛋白相关。14-3-3蛋白以磷酸丝氨酸依赖的方式与HCV核心蛋白结合,HCV核心蛋白的引入导致HepG2细胞和酵母遗传试验中Raf-1激酶活性的显著增加。此外,HCV核心蛋白14-3-3相互作用对于HCV核心蛋白激活Raf-1激酶至关重要。这些结果表明,HCV核心蛋白可能是一种新型的Raf-1激酶激活蛋白,通过与14-3-3蛋白相互作用,参与肝细胞生长调节。
Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver dysfunction in humans and is epidemiologically protein has been reported to be implicated in cell growth regulation both in vitro and in vivo, although mechanisms explaining those effects are still unclear. In the present study, we identified that members of the 14-3-3 protein family associate with HCV core protein. 14-3-3 protein bound to HCV core protein in a phosphoserine-dependent manner, Introduction of HCV core protein caused a substantial increase in Raf-1 kinase activity in HepG2 cells and in a yeast genetic assay. Furthermore, the HCV core-14-3-3 interaction was essential for Raf-1 kinase activation by HCV core protein. These results suggest that HCV core protein may represent a novel type of Raf-1 kinase-activating protein through its interaction with 14-3-3 protein and may contribute to hepatocyte growth regulation.