Activation of c-Myc contributes to bovine papillomavirus type 1 E7-induced cell proliferation
UMass Chan AffiliationsDepartment of Medicine
Document TypeJournal Article
Cell Cycle Proteins
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase Inhibitor p27
NIH 3T3 Cells
Oncogene Proteins, Viral
Proto-Oncogene Proteins c-myc
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Proteins
Medicine and Health Sciences
MetadataShow full item record
AbstractInactivation 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.
SourceJ Biol Chem. 2003 Oct 31;278(44):43163-8. Epub 2003 Aug 22. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42357
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