Krachmarov C P, Chepenik L G, Barr-Vagell S, Khalili K, Johnson E M
Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14112-7. doi: 10.1073/pnas.93.24.14112.
JC virus is activated to replicate in glial cells of many AIDS patients with neurological disorders. In human glial cells, the human immunodeficiency virus 1 (HIV-1) Tat protein activates the major late promoter of JC virus through a Tat-responsive DNA element, termed upTAR, which is a recognition site for cellular Pur alpha, a sequence-specific single-stranded DNA binding protein implicated in cell cycle control of DNA replication and transcription. Tat interacts with two leucine-rich repeats in Pur alpha to form a complex that can be immunoprecipitated from cell extracts. Tat enhances the ability of purified glutathione S-transferase-Pur alpha (GST-Pur alpha) to bind the upTAR element. Tat acts synergistically with Pur alpha, in a cell-cycle-dependent manner, to activate transcription at an upTAR element placed upstream of a heterologous promoter. Since Pur alpha is ubiquitously expressed in human cells and since PUR elements are located near many promoters and origins of replication, the Tat-Pur alpha interaction may be implicated in effects of HIV-1 throughout the full range of HIV-1-infected cells.
在许多患有神经疾病的艾滋病患者的神经胶质细胞中，JC病毒被激活并开始复制。在人类神经胶质细胞中，人类免疫缺陷病毒1（HIV-1）的Tat蛋白通过一个名为upTAR的Tat反应性DNA元件激活JC病毒的主要晚期启动子，upTAR是细胞Pur alpha的识别位点，Pur alpha是一种序列特异性单链DNA结合蛋白，与DNA复制和转录的细胞周期调控有关。Tat与Pur alpha中的两个富含亮氨酸的重复序列相互作用，形成一个可以从细胞提取物中免疫沉淀的复合物。Tat增强了纯化的谷胱甘肽S-转移酶-Pur alpha（GST-Pur alpha）结合upTAR元件的能力。Tat与Pur alpha以细胞周期依赖性方式协同作用，激活位于异源启动子上游的upTAR元件处的转录。由于Pur alpha在人类细胞中普遍表达，并且由于PUR元件位于许多启动子和复制起点附近，Tat-Pur alpha相互作用可能与HIV-1在整个HIV-1感染细胞范围内的作用有关。
