JC virus T′135, T′136 and T′165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential
JC virus T′135, T′136 and T′165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential
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DOI：
10.1080/13550280601009553
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发表时间：
2006-12-01
影响因子：
3.2
通讯作者：
Frisque, Richard J.
中科院分区：
文献类型：
--
作者：
Bollag, Brigitte;Kilpatrick, Lisa H.;Frisque, Richard J.
JC病毒（JCV）调节蛋白，大T抗原、小t抗原、T '（135）、T'（136）和T '（165），由从病毒早期前体mRNA选择性剪接的五种转录物编码。T抗原和T'蛋白共享N-末端氨基酸序列，包括LxCxE和J结构域，已知SV 40 T抗原中的基序分别介导与视网膜母细胞瘤（Rb）蛋白和Hsc 70的结合。在本研究中，产生了单独或组合表达野生型或突变型JCV T抗原和T'蛋白的G418抗性细胞系。这些细胞系用于评价每种病毒蛋白在体内结合p107和p130的能力，以及影响细胞生长特性的能力。不同的T'蛋白结合p107和p130的能力，并改变其磷酸化状态。T'蛋白定位于细胞核，并以细胞周期依赖的方式磷酸化。从巨细胞病毒启动子表达的JCV T抗原和T'蛋白未能诱导Rat 2细胞中致密灶形成，但它们确实与突变Ras蛋白合作克服细胞衰老并使大鼠胚胎成纤维细胞永生化。这些数据表明，尽管它们的序列相似性，JCV早期蛋白表现出独特的活动，在组合中，影响细胞周期调节因子的失活，多瘤病毒诱导的转化的要求。
The JC virus (JCV) regulatory proteins, large T antigen, small t antigen, T'(135), T'(136), and T'(165), are encoded by five transcripts alternatively spliced from the viral early precursor mRNA. T antigen and the T' proteins share N-terminal amino acid sequences that include the LxCxE and J domains, motifs in SV40 T antigen known to mediate binding to the retinoblastoma (Rb) proteins and Hsc70, respectively. In this study, G418-resistant cell lines were created that express wild-type or mutant JCV T antigen and T' proteins individually or in combination. These cell lines were used to evaluate the ability of each viral protein to bind p107 and p130 in vivo, and to influence cellular growth characteristics. Differences were observed in the abilities of individual T' proteins to bind p107 and p130 and to alter their phosphorylation status. The T' proteins were also found to localize to the cell's nucleus and to be phosphorylated in a cell cycle-dependent manner. JCV T antigen and T' proteins expressed from a cytomegalovirus promoter failed to induce dense focus formation in Rat2 cells, but they did cooperate with a mutant Ras protein to overcome cellular senescence and immortalize rat embryo fibroblasts. These data indicate that, despite their sequence similarities, JCV early proteins exhibit unique activities that, in combination, effect the inactivation of cell cycle regulators, a requirement for polyomavirus-induced transformation.