The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein.
The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein.
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DOI：
10.1038/ncomms14259
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发表时间：
2017-01-30
影响因子：
16.6
通讯作者：
Ryo A
中科院分区：
文献类型：
--
作者：
Miyakawa K;Nishi M;Matsunaga S;Okayama A;Anraku M;Kudoh A;Hirano H;Kimura H;Morikawa Y;Yamamoto N;Ono A;Ryo A
多种细胞蛋白和rna在其亚细胞定位中受到严格调控，以发挥其局部功能。在这里，我们报告了肿瘤抑制腺瘤性息肉病大肠蛋白（APC）指导人类免疫缺陷病毒(HIV)-1 Gag多蛋白在不同膜组分的定位和组装，从而使感染性病毒颗粒有效地产生和传播。蛋白质组学分析和随后的生物分子相互作用分析表明，APC的羧基端与Gag的基质区相互作用。APC的异位表达，而不是其家族性腺瘤性息肉病相关的截断突变体，显著提高HIV-1的产生。相反，APC的耗尽导致病毒成分的膜靶向性显著降低，导致感染性病毒粒子的生产严重损失。此外，APC促进病毒成分在病毒学突触的定向组装，从而促进细胞间病毒传播。这些发现揭示了APC在HIV-1定向传播中的意想不到的作用。肿瘤抑制因子APC是一种涉及mrna细胞内定位和WNT信号传导的多功能蛋白。在这里，Miyakawa等人表明，通过与HIV Gag前体蛋白的相互作用，APC促进了病毒成分的膜靶向和HIV的细胞间传播。
Diverse cellular proteins and RNAs are tightly regulated in their subcellular localization to exert their local function. Here we report that the tumour suppressor adenomatous polyposis coli protein (APC) directs the localization and assembly of human immunodeficiency virus (HIV)-1 Gag polyprotein at distinct membrane components to enable the efficient production and spread of infectious viral particles. A proteomic analysis and subsequent biomolecular interaction assay reveals that the carboxyl terminus of APC interacts with the matrix region of Gag. Ectopic expression of APC, but not its familial adenomatous polyposis-related truncation mutant, prominently enhances HIV-1 production. Conversely, the depletion of APC leads to a significant decrease in membrane targeting of viral components, resulting in the severe loss of production of infectious virions. Furthermore, APC promotes the directional assembly of viral components at virological synapses, thereby facilitating cell-to-cell viral transmission. These findings reveal an unexpected role of APC in the directional spread of HIV-1. The tumour suppressor APC is a multifunctional protein implicated in intracellular localization of mRNAs and WNT signalling. Here, Miyakawa et al. show that, via interaction with the HIV Gag precursor protein, APC promotes membrane targeting of viral components and cell-to-cell spread of HIV.