Regulated nucleocytoplasmic trafficking of viral gene products: A therapeutic target?
Regulated nucleocytoplasmic trafficking of viral gene products: A therapeutic target?
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DOI：
10.1016/j.bbapap.2007.08.021
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Jans, David A.
中科院分区：
文献类型：
--
作者：
Alvisi, Gualtiero;Rawlinson, Stephen M.;Jans, David A.
病毒蛋白和宿主细胞因子与它们相互作用的研究代表了一个宝贵的贡献，了解生理学以及相关的病理学的关键真核细胞过程，如细胞周期调控，信号转导和转化。类似地，核质转运的知识主要基于对病毒蛋白进行的开创性研究，这些研究使负责促进通过核孔转运的第一序列得以鉴定。对病毒蛋白质的研究还发现了几种核质调节机制，最具特征的是通过磷酸化。最近描绘的机制，磷酸化调节核输入和输出的重要的人类病原体，如人类巨细胞病毒，登革热病毒和呼吸道合胞病毒编码的关键病毒基因产物的抗病毒治疗的发展有意义。特别是，特异性和有效的激酶抑制剂的开发使得通过抑制病毒基因产物核转运的磷酸化依赖性调节来阻断病毒感染的想法成为真实的可能。此外，鸡贫血病毒（CAV）蛋白能够选择性靶向肿瘤细胞核，而不是正常细胞，通过磷酸化特异性调节，打开了癌细胞特异性核靶向的令人兴奋的可能性。因此，核质转运的研究不仅可以开发新的抗病毒方法，而且还有助于抗癌策略。(C)2007 Elsevier B.V.保留所有权利。
The study of viral proteins and host cell factors that interact with them has represented an invaluable contribution to understanding of the physiology as well as associated pathology of key eukaryotic cell processes such as cell cycle regulation, signal transduction and transformation. Similarly, knowledge of nucleocytoplasmic transport is based largely on pioneering studies performed on viral proteins that enabled the first sequences responsible for the facilitated transport through the nuclear pore to be identified. The study of viral proteins has also enabled the discovery of several nucleocytoplasmic regulatory mechanisms, the best characterized being through phosphorylation. Recent delineation of the mechanisms whereby phosphorylation regulates nuclear import and export of key viral gene products encoded by important human pathogens such as human cytomegalovirus dengue virus and respiratory syncytial virus has implications for the development of antiviral therapeutics. In particular, the development of specific and effective kinase inhibitors makes the idea of blocking viral infection by inhibiting the phosphorylation-dependent regulation of viral gene product nuclear transport a real possibility. Additionally, examination of a chicken anemia virus (CAV) protein able to target selectively into the nucleus of tumor but not normal cells, as specifically regulated by phosphorylation, opens the exciting possibility of cancer cell-specific nuclear targeting. The study of nucleoplasmic transport may thus enable the development not only of new antiviral approaches, but also contribute to anti-cancer strategies. (C) 2007 Elsevier B.V. All rights reserved.