Kaposi’s sarcoma-associated herpesvirus(KSHV)is γ-2 herpesvirus with latency and lytic replication stages in its life-cycle.The viral replication and transcription activator(RTA)is the key protein for triggering KSH...Kaposi’s sarcoma-associated herpesvirus(KSHV)is γ-2 herpesvirus with latency and lytic replication stages in its life-cycle.The viral replication and transcription activator(RTA)is the key protein for triggering KSHV lytic gene expression and replication from latency.In this review,we will discuss the gene expression program in KSHV lytic replication and latency,the regulation of the RTA expression,the RTA protein and the mechanisms that RTA utilizes to transactivate its target genes.We will focus on the RTA-mediated transactivation mechanisms,including DNA-binding,interacting with cellular co-factors and promoting repressor degradation.展开更多
复制转录激活蛋白(replication and transcription activator,RTA)是γ疱疹病毒的一个具序列保守性的蛋白质分子,由即时早期基因ORF50所编码.RTA可通过激活裂解期基因转录而使病毒进入裂解感染.鼠疱疹病毒68(MHV-68)亦属γ疱疹病毒,该...复制转录激活蛋白(replication and transcription activator,RTA)是γ疱疹病毒的一个具序列保守性的蛋白质分子,由即时早期基因ORF50所编码.RTA可通过激活裂解期基因转录而使病毒进入裂解感染.鼠疱疹病毒68(MHV-68)亦属γ疱疹病毒,该病毒能体外感染多种细胞,并且能感染实验小鼠,是研究γ疱疹病毒的良好模型.在MHV-68中,目前只有两个受RTA调控的基因被报道,但调控机制未明.之前的研究鉴定出一个新的RTA的DNA结合序列(RTA response element,RRE),以此为基础,首先通过基因比对在病毒基因组上找到具有较高同源性的核酸序列片段(ORF9p-RRE),该序列在病毒基因组上位于ORF9启动子区,通过双重荧光素酶报告基因系统证实了RTA可作用于该启动子区进而激活下游基因转录,并且该转录激活是ORF9p-RRE依赖的.凝胶阻滞电泳实验(EMSA)和染色质免疫沉淀实验(ChIP)分别证实了RTA可在体外、体内与ORF9p-RRE直接结合.研究结果初步揭示了RTA与ORF9p-RRE相互作用的机制,为深入了解RTA激活病毒基因转录的机理提供了更多依据.展开更多
文摘Kaposi’s sarcoma-associated herpesvirus(KSHV)is γ-2 herpesvirus with latency and lytic replication stages in its life-cycle.The viral replication and transcription activator(RTA)is the key protein for triggering KSHV lytic gene expression and replication from latency.In this review,we will discuss the gene expression program in KSHV lytic replication and latency,the regulation of the RTA expression,the RTA protein and the mechanisms that RTA utilizes to transactivate its target genes.We will focus on the RTA-mediated transactivation mechanisms,including DNA-binding,interacting with cellular co-factors and promoting repressor degradation.
基金National Cancer Institute 5R01CA091792-085R01CA108461-05+2 种基金1R01CA137894-01 and 1R01CA138434-01A209National Institute of Allergy and Infectious Diseases 5R01AI067037-04National Institute of Dental and Craniofacial Research5R01DE017338-03(to ESR)
文摘目的:定位survivin基因启动子中参与卡波西肉瘤相关疱疹病毒(Kaposi’s sarcoma-associated herpesvirus,KSHV)复制转录激活因子(replication and transcription activator,RTA)上调survivin表达的重要元件。方法:构建survivin基因启动子的突变报告质粒,采用萤光素酶报告基因检测和染色质免疫共沉淀技术,定位survivin基因启动子区域能与RTA相互作用的顺式元件。结果:突变GC/Sp1和p53两个结合位点启动子活性几乎完全关闭,p53顺式作用元件对RTA上调survivin基因启动子活性具有协同作用。结论:KSHV RTA能够与survivin基因启动子中的GC/Sp1和p53顺式元件相互作用,特异性地增强survivin基因启动子活性。
基金National Cancer Institute 5R01CA091792-085R01CA108461-05+2 种基金1R01CA137894-01 and 1R01CA138434-01A209National Institute of Allergy and Infectious Diseases 5R01AI067037-04National Institute of Dental and Craniofacial Research 5R01DE017338-03(to ESR)
