Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
Virology. 2013 Jul 20;442(1):38-50. doi: 10.1016/j.virol.2013.03.023. Epub 2013 Apr 17.
The ORF45 gene of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a multifunctional tegument protein. Here, we characterize the transcriptional control of the ORF45 gene and show that its promoter can be activated by ORF50 protein, a latent-lytic switch transactivator. The ORF45 promoter can also be induced by sodium butyrate (SB), a histone deacetylase inhibitor, in the absence of ORF50 protein. Although SB induces the ORF45 gene independently of ORF50, its full activation may require the presence of ORF50. Deletion and point mutation analyses revealed that two RBP-Jκ-binding sites in the ORF45 promoter confer the ORF50 responsiveness, whereas NF-Y and Sp1-binding sites mediate the response to SB. Direct binding of NF-Y, Sp1, or RBP-Jκ protein to the ORF45 promoter is required for the promoter activation induced by SB or by ORF50. In conclusion, our study demonstrates both ORF50-dependent and ORF50-independent transcriptional mechanisms operated on the activation of the ORF45 gene.
卡波氏肉瘤相关疱疹病毒（KSHV）的 ORF45 基因编码一种多功能被膜蛋白。在这里，我们描述了 ORF45 基因的转录调控，并证实其启动子可被潜伏-裂解开关反式激活因子 ORF50 蛋白激活。在没有 ORF50 蛋白的情况下，组蛋白去乙酰化酶抑制剂丁酸钠（SB）也可以诱导 ORF45 启动子。虽然 SB 可以独立于 ORF50 诱导 ORF45 基因，但它的完全激活可能需要 ORF50 的存在。缺失和点突变分析表明，ORF45 启动子中的两个 RBP-Jκ 结合位点赋予了 ORF50 反应性，而 NF-Y 和 Sp1 结合位点介导了对 SB 的反应。NF-Y、Sp1 或 RBP-Jκ 蛋白与 ORF45 启动子的直接结合对于 SB 或 ORF50 诱导的启动子激活是必需的。总之，我们的研究表明，ORF45 基因的激活涉及 ORF50 依赖和非依赖的转录机制。
