Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth.
Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth.
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核衣壳与 NPM1 相互作用并保护其免受蛋白水解裂解，增强细胞存活率，并参与 PEDV 生长
DOI：
10.1038/srep39700
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发表时间：
2017-01-03
影响因子：
4.6
通讯作者：
Feng L
中科院分区：
文献类型：
--
作者：
Shi D;Shi H;Sun D;Chen J;Zhang X;Wang X;Zhang J;Ji Z;Liu J;Cao L;Zhu X;Yuan J;Dong H;Wang X;Chang T;Liu Y;Feng L
猪流行性腹泻病毒（PEDV）在感染细胞的细胞质中复制，但其核衣壳（N）蛋白特异性地定位于细胞核。核转位的机制，以及N蛋白是否与特定的核仁成分，是未知的。在本研究中，我们证实了核仁磷蛋白nucleophosmin（NPM 1）与核仁中的N蛋白相互作用并共定位，体外结合研究表明，NPM 1与N蛋白的结合需要氨基酸148-294和NPM 1的氨基酸118-188。有趣的是，N蛋白输入到核仁是独立的NPM 1之间的细胞核和细胞质的穿梭能力。此外，NPM 1的过表达促进PEDV生长，而NPM 1的敲低抑制PEDV生长。此外，N蛋白与NPM 1的结合保护其免受caspase-3的蛋白水解降解，从而增加细胞存活。两者合计，我们的研究表明，一个特定的相互作用的N蛋白与宿主细胞蛋白NPM 1的核仁。这些结果表明，病毒策略之间的潜在联系，用于调节细胞存活活动，可能通过N蛋白与NPM 1的相互作用，防止其蛋白水解裂解，提高细胞存活，从而最终促进PEDV的复制。
Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus.In vitrobinding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV.
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影响因子：
5.4
作者：
Dinh, Phat X.;Beura, Lalit K.;Pattnaik, Asit K.
通讯作者：
Pattnaik, Asit K.
影响因子：
8
作者：
Hsu, CY;Yung, BYM
通讯作者：
Yung, BYM
DOI：
10.1111/j.1432-1033.1996.0153n.x
发表时间：
1996-04-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Li, YP;Busch, RK;Busch, H
通讯作者：
Busch, H
DOI：
10.1615/critreveukaryotgeneexpr.v13.i1.40
发表时间：
2003-01-01
影响因子：
1.6
作者：
Leung, AKL;Lamond, AI
通讯作者：
Lamond, AI
影响因子：
3
作者：
Lindström MS
通讯作者：
Lindström MS