Regulation of cyclin E gene expression by the human papillomavirus type 16 E7 oncoprotein

• Published in: Journal of general virology Vol. 80; no. 8; pp. 2103 - 2113
• Main Authors: Vogt, Beate, Zerfa{beta}-Thome, Karin, Schulze, Almut, Botz, Jurgen W, Zwerschke, Werner, Jansen-Durr, Pidder
• Format: Journal Article
• Language: English
• Published: England Soc General Microbiol 01-08-1999
• Subjects: 3T3 Cells; Animals; Binding Sites; Carrier Proteins; Cell Cycle Proteins; Cell Line; Cyclin E - genetics; DNA-Binding Proteins; Drosophila; Drosophila Proteins; E2F Transcription Factors; Gene Expression Regulation; Human papillomavirus 16; Humans; Mice; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - physiology; Papillomaviridae; Papillomavirus E7 Proteins; Promoter Regions, Genetic; Retinoblastoma-Binding Protein 1; Sp1 Transcription Factor - metabolism; Trans-Activators; Transcription Factor DP1; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-80-8-2103

Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Abt. F0301, INF 242, D-69120 Heidelberg, Germany 1
Author for correspondence: Pidder Jansen-Dürr. Present address: Institut f. Biomedizinische Alternsforschung der Österreichischen Akademie der Wissenschaften, Rennweg 10, A-6020 Innsbruck, Austria. Fax [phone]. e-mail P.Jansen- Duerr{at}oeaw.ac.at
In this study, we characterized the 5' regulatory region of the murine cyclin E gene and analysed activation of the gene by the E7 oncogene of human papillomavirus type 16 in transfection experiments. We found that the murine cyclin E promoter is composed of multiple regulatory elements, and we present evidence for at least two independent transcription units, designated P1 and P2. Overlapping binding sites for the cellular transcription factors Sp1 and E2F were identified in both promoters, and we found that E2F-mediated activation of transcription is inhibited by Sp1 in cotransfection experiments. The E2F/Sp1 binding sites contribute to transcriptional activation by E7, and the data suggest that the cyclin E gene is rendered E7-inducible through the combination of several cis -acting elements which display only weak intrinsic responsiveness to E7.