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首页> 外文期刊>Cell cycle >Poliovirus protein 3A binds and inactivates LIS1, causing block of membrane protein trafficking and deregulation of cell division.
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Poliovirus protein 3A binds and inactivates LIS1, causing block of membrane protein trafficking and deregulation of cell division.

机译：脊髓灰质炎病毒蛋白3A结合并失活LIS1，导致膜蛋白运输受阻和细胞分裂失调。

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摘要

Many viruses encode anti-apoptotic proteins that have been used as valuable tools for identification and analysis of key cellular regulators of programmed cell death. Here we demonstrate that the poliovirus protein 3A, previously shown to exhibit anti-apoptotic activity, binds and inactivates LIS1, a component of the dynein/dynactin motor complex, encoded by the gene mutated in patients with type I lissencephaly ("smooth brain"), thereby causing deregulation of endoplasmatic reticilum-to-Golgi vesicular transport, resulting in rapid disappearance of short-living receptors from the plasma membrane and loss of cell sensitivity to TNF and interferon. Truncated derivatives of LIS1, acting in a dominant negative manner, cause similar effects. However, 3A, being an endoplasmic reticulum-bound protein, locks Golgi-targeted YFP in the endoplasmatic reticilum, while expression of LIS1 mutants results in a dispersed cytoplasmic localization of the reporter protein. LIS1 dysfunction caused by ectopic expressing 3A or LIS1 mutants, as well as by overexpression of wild type LIS1, leads to cell blocking at the postmitotic stage associated with inability to undergo cytokinesis. Thus, the use of poliovirus protein as a research tool allowed us to reveal the role of cellular protein LIS1 in membrane protein trafficking, maintenance of Golgi integrity, surface presentation of unstable receptors, cell sensitivity to TNF-induced apoptosis and cell cycle progression.
机译：许多病毒编码抗凋亡蛋白，这些蛋白已被用作鉴定和分析程序性细胞死亡的关键细胞调节剂的有价值的工具。在这里，我们证明了脊髓灰质炎病毒蛋白3A（先前显示具有抗凋亡活性）结合并失活了动力蛋白/动力蛋白运动复合体的组成部分LIS1，该蛋白由I型轻型脑病（“平滑脑”）患者突变的基因编码，从而引起内质网至高尔基体囊泡运输的失控，导致短生存受体从质膜迅速消失，并使细胞对TNF和干扰素的敏感性下降。 LIS1的截短导数以负的主要方式起作用，会产生类似的效果。但是，3A是一种与内质网结合的蛋白，可将靶向高尔基体的YFP锁定在内质网中，而LIS1突变体的表达导致报告蛋白的胞质分散。由异位表达3A或LIS1突变体以及野生型LIS1的过表达引起的LIS1功能障碍，导致在有丝分裂后阶段的细胞阻断与无法进行胞质分裂有关。因此，使用脊髓灰质炎病毒蛋白作为研究工具使我们能够揭示细胞蛋白LIS1在膜蛋白运输，维持高尔基体完整性，不稳定受体的表面呈递，细胞对TNF诱导的细胞凋亡和细胞周期进程的敏感性中的作用。

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