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Activation of RB/E2F signaling pathway is required for the modulation of hepatitis C virus core protein-induced cell growth in liver and non-liver cells

机译:RB / E2F信号通路的激活是调节丙型肝炎病毒核心蛋白诱导的肝和非肝细胞生长的细胞所必需的

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Hepatitis C virus (HCV) core protein is a multifunctional protein that affects transcription and cell growth in vitro and in vivo. Here, we confirm the proliferative activities of core protein in liver and non-liver cells and delineate part of the mechanism whereby core protein promotes cell growth. We show that core protein suppresses the expression of tumor suppressor protein p53 and cyclin-dependent kinase (CDK) inhibitor p21 and enhances the activation of cyclin-dependent kinase 2 (CDK2), the phosphorylation of retinoblastoma (Rb), the activation of the transcription factor E2F-1, and the expression of E2F-1 and S phase kinase-interacting protein 2 (SKP2) genes. Pretreatment of core protein-expressing cells with the inhibitor of CDK2, Butyrolactone 1, abolished the phosphorylation of Rb, the activation of E2F-1, and inhibited the expression of E2F-1 gene and cell growth induced. Consistent with these findings, we define a new signaling pathway whereby the HCV core protein mediates cell growth in infected cells. (C) 2004 Elsevier Inc. All rights reserved.
机译:丙型肝炎病毒(HCV)核心蛋白是一种多功能蛋白,可在体外和体内影响转录和细胞生长。在这里,我们确认了核心蛋白在肝脏和非肝细胞中的增殖活性,并描绘了核心蛋白促进细胞生长的部分机制。我们显示核心蛋白抑制肿瘤抑制蛋白p53和细胞周期蛋白依赖性激酶(CDK)抑制剂p21的表达,并增强细胞周期蛋白依赖性激酶2(CDK2)的激活,视网膜母细胞瘤(Rb)的磷酸化,转录的激活因子E2F-1,以及E2F-1和S期激酶相互作用蛋白2(SKP2)基因的表达。用CDK2抑制剂丁内酯1预处理表达核心蛋白的细胞,消除了Rb的磷酸化,E2F-1的激活,并抑制了E2F-1基因的表达和诱导的细胞生长。与这些发现一致,我们定义了一种新的信号传导途径,HCV核心蛋白可通过该途径介导感染细胞中的细胞生长。 (C)2004 Elsevier Inc.保留所有权利。

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