首页> 美国卫生研究院文献>Journal of Virology >Direct Interactions of Kaposis Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Protein with the Cellular Protein Octamer-1 and DNA Are Critical for Specifying Transactivation of a Delayed-Early Promoter and Stimulating Viral Reactivation
【2h】

Direct Interactions of Kaposis Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Protein with the Cellular Protein Octamer-1 and DNA Are Critical for Specifying Transactivation of a Delayed-Early Promoter and Stimulating Viral Reactivation

机译:卡波西氏肉瘤相关疱疹病毒/人类疱疹病毒8 ORF50 / Rta蛋白与细胞蛋白Octamer-1和DNA的直接相互作用对于指定延迟早期启动子的反式激活和刺激病毒激活至关重要。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

The Kaposi's sarcoma-associated herpesvirus (KSHV) delayed-early K-bZIP promoter contains an ORF50/Rta binding site whose sequence is conserved with the ORF57 promoter. Mutation of the site in the full-length K-bZIP promoter reduced Rta-mediated transactivation by greater than 80%. The K-bZIP element contains an octamer (Oct) binding site that overlaps the Rta site and is well conserved with Oct elements found in the immediate-early promoters of herpes simplex virus type 1(HSV-1). The cellular protein Oct-1, but not Oct-2, binds to the K-bZIP element in a sequence-specific fashion in vitro and in vivo and stimulates Rta binding to the promoter DNA. The coexpression of Oct-1 enhances Rta-mediated transactivation of the wild type but not the mutant K-bZIP promoter, and Oct-1 and Rta proteins bind to each other directly in vitro. Mutations of Rta within an amino acid sequence conserved with HSV-1 virion protein 16 eliminate Rta's interactions with Oct-1 and K-bZIP promoter DNA but not RBP-Jk. The binding of Rta to both Oct-1 and DNA contributes to the transactivation of the K-bZIP promoter and viral reactivation, and Rta mutants deficient for both interactions are completely debilitated. Our data suggest that the Rta/Oct-1 interaction is essential for optimal KSHV reactivation. Transfections of mouse embryo fibroblasts and an endothelial cell line suggest cell-specific differences in the requirement for Oct-1 or RBP-Jk in Rta-mediated transactivation of the K-bZIP promoter. We propose a model in which Rta transactivation of the promoter is specified by the combination of DNA binding and interactions with several cellular DNA binding proteins including Oct-1.
机译:卡波氏肉瘤相关疱疹病毒(KSHV)延迟早期K-bZIP启动子包含一个ORF50 / Rta结合位点,其序列与ORF57启动子保守。全长K-bZIP启动子中位点的突变使Rta介导的反式激活降低了80%以上。 K-bZIP元件包含一个与Rta位置重叠的八聚体(Oct)结合位点,并与在单纯疱疹病毒1型(HSV-1)的早期早期启动子中发现的Oct元件非常保守。细胞蛋白Oct-1,但不是Oct-2,在体外和体内均以序列特异性的方式与K-bZIP元件结合,并刺激Rta与启动子DNA结合。 Oct-1的共表达增强了Rta介导的野生型反式激活,但不增强突变K-bZIP启动子,并且Oct-1和Rta蛋白直接在体外彼此结合。在HSV-1病毒粒子蛋白16保守的氨基酸序列内,Rta的突变消除了Rta与Oct-1和K-bZIP启动子DNA的相互作用,但没有消除RBP-Jk。 Rta与Oct-1和DNA的结合有助于K-bZIP启动子的反式激活和病毒的重新激活,并且两种相互作用均不足的Rta突变体完全虚弱。我们的数据表明,Rta / Oct-1相互作用对于最佳KSHV重新激活至关重要。小鼠胚胎成纤维细胞和内皮细胞系的转染表明Rta介导的K-bZIP启动子在Oct-1或RBP-Jk的需求中存在细胞特异性差异。我们提出了一个模型,其中启动子的Rta反式激活是通过DNA结合以及与包括Oct-1在内的几种细胞DNA结合蛋白相互作用的结合来确定的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号