The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV Woe 1 production
The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV Woe 1 production
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DOI：
10.1073/pnas.0408717102
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发表时间：
2005-02-01
影响因子：
11.1
通讯作者：
Reiss, Y
中科院分区：
文献类型：
--
作者：
Alroy, I;Tuvia, S;Reiss, Y
人类免疫缺陷病毒1型(HIV-1)可聚集在晚期内吞体内的质膜或膜上。现在，我们报道了人泛素连接酶POSH(大量SH3S；hPOSH)，一种反式高尔基网络相关蛋白，在将HIV-1靶向质膜中发挥重要作用。小分子抑制性RNA介导的hPOSH沉默可阻断病毒分泌和Gag质膜定位。重新引入天然的，但不是无名指突变体的hPOSH，恢复了hPOSH耗竭细胞中病毒的释放和Gag质膜的定位。此外，环指突变体hPOSH的表达抑制了病毒的释放，并诱导了正常细胞内GAG的积累。总之，我们的结果确定了艾滋病毒生物发生中以前未描述的步骤，并表明hPOSH介导的泛素化在反式高尔基体网络的蛋白质分类中具有直接功能。因此，hPOSH可能是治疗干预的有用宿主靶点。
HIV type 1 (HIV-1) was shown to assemble either at the plasma membrane or in the membrane of late endosomes. Now, we report an essential role for human ubiquitin ligase POSH (Plenty of SH3s; hPOSH), a trans-Golgi network-associated protein, in the targeting of HIV-1 to the plasma membrane. Small inhibitory RNA-mediated silencing of hPOSH ablates virus secretion and Gag plasma membrane localization. Reintroduction of native, but not a RING finger mutant, hPOSH restores virus release and Gag plasma membrane localization in hPOSH-depleted cells. Furthermore, expression of the RING finger mutant hPOSH inhibits virus release and induces accumulation of intracellular Gag in normal cells. Together, our results identify a previously undescribed step in HIV biogenesis and suggest a direct function for hPOSH-mediated ubiquitination in protein sorting at the trans-Golgi network. Consequently, hPOSH may be a useful host target for therapeutic intervention.