Role of cdk 9 in the Optimization of Expression of the Genes Regulated by ICP 22 of Herpes Simplex Virus 1 Lizette
Role of cdk 9 in the Optimization of Expression of the Genes Regulated by ICP 22 of Herpes Simplex Virus 1 Lizette
复制标题
DOI：
--
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Marjorie B. Kovler
中科院分区：
文献类型：
--
作者：
Marjorie B. Kovler
ICP 22是一种多功能单纯疱疹病毒I（HSV-1）调节蛋白，其调节由UL 38、UL 41和US 11例示的晚期（2）蛋白的子集的积累。ICP 22结合细胞周期蛋白依赖性激酶9（cdk 9），但不结合cdk 7，并且该复合物与病毒蛋白激酶一起在体外磷酸化RNA聚合酶II（Pol II）的羧基末端。cdk 9及其伴侣，细胞周期蛋白T变体的主要功能是延长RNA转录物，尽管也有报道与转录物的起始和加工相关的功能。我们报告了两个系列的实验，旨在探测cdk 9在感染细胞中的作用。首先，感染的细胞用5，6-二氯-1-D-呋喃核糖基苯并咪唑（DRB）处理，DRB是cdk 9的特异性抑制剂。在用DRB处理的细胞中，主要作用是由ICP 22调节的病毒RNA和蛋白质的积累。、或不受ICP 22调节的蛋白质的积累不受药物的影响。用DRB获得的结果在用靶向cdk 9 mRNA的小干扰RNA（siRNA）转染的细胞中重复。有趣的是，DRB和siRNA降低了ICP 22的水平，但没有降低其他基因产物的水平。此外，cdk 9和ICP 22似乎与RNA Pol II在野生型病毒感染的细胞中共定位，但在UL 13感染的细胞中不共定位。我们的结论是cdk 9起着关键作用，在优化的基因表达的ICP 22和CDK 9在HSV-1感染的细胞中的一个功能可能是把ICP 22到RNA Pol II转录复合物。
ICP22 is a multifunctional herpes simplex virus 1 (HSV-1) regulatory protein that regulates the accumulation of a subset of late ( 2) proteins exemplified by UL38, UL41, and US11. ICP22 binds the cyclin-dependent kinase 9 (cdk9) but not cdk7, and this complex in conjunction with viral protein kinases phosphorylates the carboxyl terminus of RNA polymerase II (Pol II) in vitro. The primary function of cdk9 and its partners, the cyclin T variants, is in the elongation of RNA transcripts, although functions related to the initiation and processing of transcripts have also been reported. We report two series of experiments designed to probe the role of cdk9 in infected cells. In the first, infected cells were treated with 5,6-dichloro-1-D-ribofuranosylbenzimidazole (DRB), a specific inhibitor of cdk9. In cells treated with DRB, the major effect was in the accumulation of viral RNAs and proteins regulated by ICP22. The accumulation of , , or proteins not regulated by ICP22 was not affected by the drug. The results obtained with DRB were duplicated in cells transfected with small interfering RNA (siRNA) targeting cdk9 mRNAs. Interestingly, DRB and siRNA reduced the levels of ICP22 but not those of other gene products. In addition, cdk9 and ICP22 appeared to colocalize with RNA Pol II in wild-type-virus-infected cells but not in UL13-infected cells. We conclude that cdk9 plays a critical role in the optimization of expression of genes regulated by ICP22 and that one function of cdk9 in HSV-1-infected cells may be to bring ICP22 into the RNA Pol II transcriptional complex.