THE ZTA TRANSACTIVATOR INVOLVED IN INDUCTION OF LYTIC CYCLE GENE-EXPRESSION IN EPSTEIN-BARR VIRUS-INFECTED LYMPHOCYTES BINDS TO BOTH AP-1 AND ZRE SITES IN TARGET PROMOTER AND ENHANCER REGIONS
THE ZTA TRANSACTIVATOR INVOLVED IN INDUCTION OF LYTIC CYCLE GENE-EXPRESSION IN EPSTEIN-BARR VIRUS-INFECTED LYMPHOCYTES BINDS TO BOTH AP-1 AND ZRE SITES IN TARGET PROMOTER AND ENHANCER REGIONS
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DOI：
10.1128/jvi.64.3.1143-1155.1990
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发表时间：
1990-03-01
影响因子：
5.4
通讯作者：
HAYWARD, SD
中科院分区：
文献类型：
--
作者：
LIEBERMAN, PM;HARDWICK, JM;HAYWARD, SD
EB病毒（EBV）的BZLF 1或zta立即早期基因编码33千道尔顿磷酸化核蛋白，当引入潜伏感染的B淋巴细胞时，其是EBV裂解周期的特异性转录激活因子。我们以前已经表明，不同的EBV DSL靶启动子包含两个zta反应区，一个在最小启动子内，另一个在上游淋巴细胞依赖性增强子区。在这项研究中，我们使用足迹法和凝胶流动性阻滞试验，揭示细菌合成的Zta融合蛋白直接绑定到DSL内的6个TGTGCAA样基序。四个Zta结合位点位于最小启动子内的细胞TATA和CAAT因子结合位点附近，两个定位在增强子区域内。含有这些Zta结合位点的单拷贝寡核苷酸赋予Zta对异源启动子的响应性。此外，Zta蛋白具有与c-Fos、c-Jun、GCN 4和CREB蛋白家族的保守DNA结合区相似的碱性结构域，证明其直接结合胶原酶12-O-十四烷酰基佛波醇-13-乙酸酯反应元件中的共有AP-1位点。与zta共转染还反式激活了含有插入的野生型12-O-十四烷酰基佛波醇-13-乙酸酯反应元件寡核苷酸的靶报告基因。细胞AP-1结合活性被证明是低的潜伏性EBV感染的Raji细胞，但诱导（与Zta蛋白）激活后的裂解周期与12-O-十四酰基佛波醇-13-乙酸酯。我们的结论是，EB病毒可能已经捕获和修改的细胞基因编码的c-jun样DNA结合蛋白在其进化的分歧，从其他疱疹病毒，这种蛋白质是用来专门重定向转录活性对EBV裂解周期基因在感染细胞中的表达。
The BZLF1 or zta immediate-early gene of Epstein-Barr virus (EBV) encodes a 33-kilodalton phosphorylated nuclear protein that is a specific transcriptional activator of the EBV lytic cycle when introduced into latently infected B lymphocytes. We have shown previously that the divergent EBV DSL target promoter contains two zta-response regions, one within the minimal promoter and the other in an upstream lymphocyte-dependent enhancer region. In this study, we used footprinting and gel mobility retardation assays to reveal that bacterially synthesized Zta fusion proteins bound directly to six TGTGCAA-like motifs within DSL. Four of the Zta-binding sites lay adjacent to cellular TATA and CAAT factor-binding sites within the minimal promoter, and two mapped within the enhancer region. Single-copy oligonucleotides containing these Zta-binding sites conferred Zta responsiveness to heterologous promoters. In addition, the Zta protein, which possesses a similar basic domain to the conserved DNA-binding region of the c-Fos, c-Jun, GCN4, and CREB protein family, proved to bind directly to the consensus AP-1 site in the collagenase 12-O-tetradecanoylphorbol-13-acetate response element. Cotransfected with zta also trans activated a target reporter gene contained inserted wild-type 12-O-tetradecanoylphorbol-13-acetate response element oligonucleotides. Cellular AP-1 binding activity proved to be low in latently EBV-infected Raji cells but was induced (together with Zta protein) after activation of the lytic cycle with 12-O-tetradecanoylphorbol-13-acetate. We conclude that EBV may have captured and modified a cellular gene encoding a c-jun-like DNA-binding protein during its evolutionary divergency from other herpesviruses and that this protein is used to specifically redirect transcriptional activity toward expression of EBV lytic-cycle genes in infected cells.