Regulation of p53 Gene Expression by a Poxviral Transcription Factor

Abstract

Identification of regulators of p53 expression is a crucial step in understanding the diverse functions of p53 and its role in cellular homeostasis and responsiveness to insult. Several viral proteins inactivate p53 as a modulator of cell cycle progression and apoptosis. Here, we report that a unique leporipoxviral transcription factor greatly increases levels of p53 mRNA. C7, an early transcription factor from malignant rabbit fibroma virus (MV), is an important determinant of MV virulence. Its effects on cellular gene expression were studied both during MV infection and in isolation, with C7 DNA cloned into a pKC4 expression plasmid. In both settings, C7 caused increased p53 mRNA levels. The increased p53 mRNA reflected new transcription. C7-induced increased transcription was selective: mRNAs for some cellular genes increased but those for many other genes (e.g., Bcl2) were unchanged. Immunoblot and immunohistochemical analysis of pKC7-transfected and MV-infected cells showed that increased transcription led to an increase in p53 protein. EMSA analysis suggested that C7 bound the human p53 promoter between −240 and −614 bp. These studies document the direct effects of a viral transcription factor on cellular gene expression, specifically that it upregulates p53 transcription.