The neural F-box protein NFB42 mediates the nuclear export of the herpes simplex virus type 1 replication initiator protein (UL9 protein) after viral infection
The neural F-box protein NFB42 mediates the nuclear export of the herpes simplex virus type 1 replication initiator protein (UL9 protein) after viral infection
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DOI：
10.1073/pnas.0400738101
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发表时间：
2004-03-23
影响因子：
11.1
通讯作者：
Lehman, IR
中科院分区：
文献类型：
--
作者：
Eom, CY;Heo, WD;Lehman, IR
神经F-box 42-kDa蛋白（NFB 42）是SCFNFB 42 E3泛素连接酶的一个组成部分，在大脑的所有主要区域中表达;在非神经元组织中未检测到。我们之前鉴定出NFB 42是单纯疱疹病毒1型（HSV-1）UL 9蛋白（病毒复制启动子）的结合伴侣，并表明NFB 42和UL 9在人胚肾（293 T）细胞中的共表达导致水平显着降低。UL 9蛋白。我们现在已经发现，HSV-1感染促进了NFB 42在293 T细胞和原代海马神经元中的胞质溶胶和细胞核之间的穿梭，允许NFB 42与定位于细胞核中的磷酸化UL 9蛋白结合。这种相互作用介导UL 9蛋白从细胞核输出到胞质溶胶，导致其通过26 S蛋白酶体的泛素化和降解。由于UL 9蛋白与其他病毒和细胞因子一起沿着的核内定位是病毒DNA复制的必要步骤，因此通过其与NFB 42的特异性相互作用，借助于核输出，神经元中UL 9蛋白的降解可阻止HSV-1的主动复制并促进神经元潜伏。
The neural F-box 42-kDa protein (NFB42) is a component of the SCFNFB42 E3 ubiquitin ligase that is expressed in all major areas of the brain; it is not detected in nonneuronal tissues. We previously identified NFB42 as a binding partner for the herpes simplex virus 1 (HSV-1) UL9 protein, the viral replication-initiator, and showed that coexpression of NFB42 and UL9 in human embryonic kidney (293T) cells led to a significant decrease in the level of UL9 protein. We have now found that HSV-1 infection promotes the shuttling of NFB42 between the cytosol and the nucleus in both 293T cells and primary hippocampal neurons, permitting NFB42 to bind to the phosphorylated UL9 protein, which is localized in the nucleus. This interaction mediates the export of the UL9 protein from the nucleus to the cytosol, leading to its ubiquitination and degradation via the 26S proteasome. Because the intranuclear localization of the UL9 protein, along with other viral and cellular factors, is an essential step in viral DNA replication, degradation of the UL9 protein in neurons by means of nuclear export through its specific interaction with NFB42 may prevent active replication and promote neuronal latency of HSV-1.