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

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.