Activation of c-Myc contributes to bovine papillomavirus type 1 E7-induced cell proliferation

UMMS Affiliation

Department of Medicine

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Animals; Bromodeoxyuridine; CDC2-CDC28 Kinases; Cell Cycle Proteins; Cell Division; Cyclin A; Cyclin E; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p27; DNA; Down-Regulation; Flow Cytometry; Immunoblotting; Luciferases; Mice; NIH 3T3 Cells; Oncogene Proteins, Viral; Plasmids; Proto-Oncogene Proteins c-myc; Retinoblastoma Protein; Reverse Transcriptase Polymerase Chain Reaction; S Phase; Trans-Activation (Genetics); Transfection; Tumor Suppressor Proteins; Up-Regulation


Life Sciences | Medicine and Health Sciences


Inactivation of the tumor suppressor pRB by the human papillomavirus (HPV) oncoprotein E7 is a mechanism by which HPV promotes cell growth. The bovine papillomavirus type 1 (BPV-1) E7 does not bind pRB efficiently yet is required for full transformation of murine cells by BPV-1. In the present study, we investigated the mechanism of BPV-1 E7-induced cell proliferation. Our studies indicate that expression of BPV-1 E7 induces DNA synthesis and stimulates cells to enter S phase in quiescent cells. The induction of cell proliferation by BPV-1 E7 can occur in the retinoblastoma gene (Rb)-null cells, suggesting an Rb-independent mechanism. Consistent with this observation, BPV-1 E7 does not efficiently activate the transcription of the E2F family of transcription factors (E2F)-responsive promoters. Notably, c-Myc is able to induce cells to enter S phase in quiescent cells through an Rb/E2F-independent pathway. Significantly, c-Myc levels are increased in BPV-1 E7-expressing cells. Moreover, expression of a dominant negative c-Myc mutant inhibited BPV-1 E7-induced DNA synthesis. Consistent with the notion that c-Myc could down-regulate p27 and activate Cdk2, p27 level is decreased while both cyclin A and cyclin E-associated kinase activities are up-regulated in BPV-1 E7-expressing cells. These studies indicate an important role for c-Myc in BPV-1 E7-induced cell proliferation.

DOI of Published Version



J Biol Chem. 2003 Oct 31;278(44):43163-8. Epub 2003 Aug 22. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of biological chemistry

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