Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules - Role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation
Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules - Role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation
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DOI：
10.1074/jbc.m411499200
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Sawa, H
中科院分区：
文献类型：
--
作者：
Suzuki, T;Okada, Y;Sawa, H
人多瘤病毒JC病毒（JCV）是致死性脱髓鞘疾病进行性多灶性白质脑病的病原体，并编码六种主要蛋白质，包括agnoprotein。在jcv感染的细胞中，Agnoprotein与微管共定位，但其功能尚不完全清楚。我们现在已经在人脑cDNA文库的酵母双杂交筛选中鉴定出束状和延伸蛋白zeta 1 （FEZ1）是与JCV agnoprotein相互作用的蛋白。体外结合实验表明，agnoprotein与FEZ1和微管直接相互作用。微管共沉淀实验显示FEZ1也与微管结合，并且agnoprotein诱导FEZ1与微管分离。Agnoprotein抑制FEZ1对PC12细胞神经突生长的促进作用。相反，FEZ1的过表达抑制了JCV感染细胞中JCV蛋白的表达和细胞内运输。这些结果表明，FEZ1通过与微管的相互作用促进神经突的延伸，而agnoprotein通过诱导FEZ1与微管的分离促进JCV的繁殖。
The human polyomavirus JC virus (JCV) is the causative agent of a fatal demyelinating disease, progressive multifocal leukoencephalopathy, and encodes six major proteins, including agnoprotein. Agnoprotein colocalizes with microtubules in JCV-infected cells, but its function is not fully understood. We have now identified fasciculation and elongation protein zeta 1 (FEZ1) as a protein that interacted with JCV agnoprotein in a yeast two-hybrid screen of a human brain cDNA library. An in vitro binding assay showed that agnoprotein interacted directly with FEZ1 and microtubules. A microtubule co-sedimentation assay revealed that FEZ1 also associates with microtubules and that agnoprotein induces the dissociation of FEZ1 from microtubules. Agnoprotein inhibited the promotion by FEZ1 of neurite outgrowth in PC12 cells. Conversely, overexpression of FEZ1 suppressed JCV protein expression and intracellular trafficking in JCV-infected cells. These results suggest that FEZ1 promotes neurite extension through its interaction with microtubules, and that agnoprotein facilitates JCV propagation by inducing the dissociation of FEZ1 from microtubules.