Activation of the Epstein-Barr virus DNA polymerase promoter by the BRLF1 immediate-early protein is mediated through USF and E2F
Activation of the Epstein-Barr virus DNA polymerase promoter by the BRLF1 immediate-early protein is mediated through USF and E2F
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DOI：
10.1128/jvi.70.4.2545-2555.1996
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发表时间：
1996-04-01
影响因子：
5.4
通讯作者：
Pagano, JS
中科院分区：
文献类型：
--
作者：
Liu, CN;Sista, ND;Pagano, JS
Epstein-Barr病毒（EBV）DNA聚合酶（pol）对于在生产性EBV感染期间病毒基因组的复制是必需的。我们以前曾报道，EBV DNA pol启动子，TATA-少，组成性失活，被EBV感染的淋巴细胞中表达立即早期病毒反式激活因子BZLF 1 Z和BRLF 1（R）的基因组克隆激活。在这里，我们证明，R单独足以激活EBV阴性B细胞中的pol启动子。与R蛋白直接结合的其他早期启动子不同，它对pol启动子的作用似乎不涉及直接的DNA结合机制。相反，我们发现两种细胞转录因子，一种上游刺激因子USF和一种E2 F蛋白家族成员，分别在-795至-786和-186至-170位置直接与pol启动子结合，这两个区域先前被鉴定为对pol启动子的激活很重要。这两个位点对EBV未感染的B细胞中R对pol启动子的反式激活有贡献或至关重要。这些数据表明，R立即早期蛋白可以通过USP和E2 F激活关键的早期EBV启动子（pol）。
The Epstein-Barr virus (EBV) DNA polymerase (pol) is essential for the replication of viral genomes during productive EBV infection. We have previously reported that the EBV DNA pol promoter, which is TATA-less and constitutively inactive, is activated by a genomic clone expressing both immediate-early viral transactivators, BZLF1Z and BRLF1 (R), in EBV-infected lymphoid cells. Here we demonstrate that R alone is sufficient to activate the pol promoter in EBV-negative B cells. Unlike other early promoters to which the R protein binds directly, its effect on the pol promoter does not appear to involve a direct DNA-binding mechanism. Instead, we found that two cellular transcription factors, an upstream stimulatory factor USF, and a member of the E2F family of proteins, bind directly to the pol promoter at positions -795 to -786 and -186 to -170, respectively, regions previously identified as important for activation of the pol promoter. These two sites contribute to or are essential for transactivation of the pol promoter by R in EBV-noninfected B cells. These data suggest that the R immediate-early protein may activate a key early EBV promoter (pol) through both USP and E2F.