Jupp R, Hoffmann S, Stenberg R M, Nelson J A, Ghazal P
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201.
J Virol. 1993 Dec;67(12):7539-46. doi: 10.1128/JVI.67.12.7539-7546.1993.
The major immediate-early gene of human cytomegalovirus encodes several isoforms of an immediate-early protein which has distinct transcriptional regulatory properties. The IE86 isoform autorepresses the major immediate-early promoter by directly binding the cis repression signal element located between the TATA box and the mRNA cap site. In addition to this activity, IE86 stimulates other viral and cellular promoters. One mechanism by which eukaryotic regulatory proteins are thought to stimulate transcription is by contacting one or more general transcription factors. We show that the IE86 protein physically interacts with the DNA-binding subunit (TATA-binding protein) human transcription factor IID via the TATA-binding protein-contacting domain in the N terminus of IE86. In a mobility shift assay, IE86 was also observed to stabilize the binding of TATA-binding protein to promoter DNA. The domains within IE86 responsible for mediating transactivation and repression functioned independently. These experiments thus demonstrate the elegant ability of human cytomegalovirus to join different protein domains to produce distinct multifunctional proteins.
人类巨细胞病毒的主要立即早期基因编码一种具有不同转录调控特性的立即早期蛋白的几种异构体。IE86异构体通过直接结合位于TATA框和mRNA帽位点之间的顺式抑制信号元件来自动抑制主要立即早期启动子。除了这种活性外，IE86还能刺激其他病毒和细胞启动子。真核调节蛋白被认为刺激转录的一种机制是通过与一种或多种通用转录因子接触。我们发现IE86蛋白通过IE86 N端的TATA结合蛋白接触结构域与DNA结合亚基（TATA结合蛋白）人类转录因子IID发生物理相互作用。在迁移率变动分析中，还观察到IE86能稳定TATA结合蛋白与启动子DNA的结合。IE86中负责介导反式激活和抑制的结构域独立发挥作用。因此，这些实验证明了人类巨细胞病毒将不同蛋白结构域结合以产生不同多功能蛋白的出色能力。
