THE BZIP TRANSACTIVATOR OF EPSTEIN-BARR-VIRUS, BZLF1, FUNCTIONALLY AND PHYSICALLY INTERACTS WITH THE P65 SUBUNIT OF NF-KAPPA-B
THE BZIP TRANSACTIVATOR OF EPSTEIN-BARR-VIRUS, BZLF1, FUNCTIONALLY AND PHYSICALLY INTERACTS WITH THE P65 SUBUNIT OF NF-KAPPA-B
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DOI：
10.1128/mcb.14.3.1939
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发表时间：
1994-03-01
影响因子：
5.3
通讯作者：
KENNEY, SC
中科院分区：
文献类型：
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作者：
GUTSCH, DE;HOLLEYGUTHRIE, EA;KENNEY, SC
EB病毒（EBV）BZLF 1（Z）立即早期反式激活因子启动B细胞中潜伏性和生产性感染之间的转换。Z蛋白与碱性亮氨酸拉链蛋白c-Fos具有同源性，反式激活几种复制周期蛋白的启动子。Z对EBV BMRF 1启动子的反式激活效率依赖于细胞类型。在B细胞中，EBV通常以潜伏形式存在，Z不能有效地激活BMRF 1启动子。我们已经发现细胞因子NF-κ B的p65组分抑制几种EBV启动子的反式激活。此外，NF-κ B的抑制剂I κ B α可增强Z诱导的B细胞系Raji中的反式激活。使用谷胱甘肽S-转移酶融合蛋白和免疫共沉淀研究，我们证明了Z和p65之间的直接相互作用。这种需要Z的二聚化结构域和p65的Rel同源结构域的物理相互作用可以在体外和体内证明。NF-κ B p65或其他Rel家族蛋白对Z反式激活功能的抑制可能导致B细胞中Z反式激活因子功能的无效，并且可能是维持B细胞特异性病毒潜伏期的机制。
The Epstein-Barr virus (EBV) BZLF1 (Z) immediate-early transactivator initiates the switch between latent and productive infection in B cells. The Z protein, which has homology to the basic leucine zipper protein c-Fos, transactivates the promoters of several replicative cycle proteins. Transactivation efficiency of the EBV BMRF1 promoter by Z is cell type dependent. In B cells, in which EBV typically exists in a latent form, Z activates the BMRF1 promoter inefficiently. We have discovered that the p65 component of the cellular factor NF-kappa B inhibits transactivation of several EBV promoters by Z. Furthermore, the inhibitor of NF-kappa B, I kappa B alpha, can augment Z-induced transactivation in the B-cell line Raji. Using glutathione S-transferase fusion proteins and coimmunoprecipitation studies, we demonstrate a direct interaction between Z and p65. This physical interaction, which requires the dimerization domain of Z and the Rel homology domain of p65, can be demonstrated both in vitro and in vivo. Inhibition of Z transactivation function by NF-kappa B p65, or possibly by other Rel family proteins, may contribute to the inefficiency of Z transactivator function in B cells and may be a mechanism of maintaining B-cell-specific viral latency.