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人类巨细胞病毒IE2 86 kDa蛋白可提高人成纤维细胞中p53的水平并反式激活p53启动子。

The human cytomegalovirus IE2 86 kDa protein elevates p53 levels and transactivates the p53 promoter in human fibroblasts.

作者信息

Muganda P, Carrasco R, Qian Q

机构信息

Department of Biological Sciences and Health Research Center, Southern University, Baton Rouge, LA 70813, USA.

出版信息

Cell Mol Biol (Noisy-le-grand). 1998 Mar;44(2):321-31.

PMID:9593583
Abstract

Human cytomegalovirus (HCMV), a herpesvirus, has previously been reported to elevate cellular p53 levels within infected human fibroblasts. Since this elevation was reported to be due to the expression of HCMV immediate early (IE) gene products within the fibroblasts, and the HCMV immediate early region encodes several predominant proteins, the identity of the protein responsible for this elevation was investigated. We report that the HCMV IE2 86 kDa protein was clearly found to be the major immediate early protein responsible for elevating p53 levels within the fibroblasts. We also report that the HCMV IE2 86 kDa protein was found to transactivate the p53 promoter 5-6 fold, thus explaining the 5-6 fold rate of increased p53 protein synthesis we find in the HCMV infected fibroblasts. Since transactivation of the p53 promoter was observed in IE2 86 kDa transfected as well as in HCMV infected fibroblasts, transactivation of the p53 gene, therefore, is part of the mechanism HCMV uses to elevate p53 levels in infected fibroblasts. This is the first report to implicate the HCMV IE2 86 kDa protein in the elevation of p53 levels in fibroblasts, as well as in the transactivation of the p53 promoter in these cells.

摘要

人巨细胞病毒(HCMV)是一种疱疹病毒,此前有报道称其可提高感染的人成纤维细胞内的细胞p53水平。由于据报道这种升高是由于成纤维细胞内HCMV即刻早期(IE)基因产物的表达,且HCMV即刻早期区域编码几种主要蛋白质,因此对负责这种升高的蛋白质的身份进行了研究。我们报告称,明确发现HCMV IE2 86 kDa蛋白是负责提高成纤维细胞内p53水平的主要即刻早期蛋白。我们还报告称,发现HCMV IE2 86 kDa蛋白可使p53启动子反式激活5至6倍,从而解释了我们在HCMV感染的成纤维细胞中发现的p53蛋白合成增加5至6倍的速率。由于在转染了IE2 86 kDa的细胞以及HCMV感染的成纤维细胞中均观察到了p53启动子的反式激活,因此,p53基因的反式激活是HCMV用于提高感染的成纤维细胞中p53水平的机制的一部分。这是首次报道HCMV IE2 86 kDa蛋白与成纤维细胞中p53水平的升高以及这些细胞中p53启动子的反式激活有关。

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