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

Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Abt. F0301, INF 242, D-69120 Heidelberg, Germany¹

Author for correspondence: Pidder Jansen-Dürr. Present address: Institut f. Biomedizinische Alternsforschung der Österreichischen Akademie der Wissenschaften, Rennweg 10, A-6020 Innsbruck, Austria. Fax +43 512 583919 8. 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.

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