Document Detail

The human papillomavirus type 16 E5 oncoprotein synergizes with EGF-receptor signaling to enhance cell cycle progression and the down-regulation of p27(Kip1).
MedLine Citation:
PMID:  20144468     Owner:  NLM     Status:  MEDLINE    
E5 oncoprotein activity from high risk human papillomaviruses (HPVs) is associated with growth factor receptor signaling, but the function of this protein is not well understood. In this study, we investigated the role of HPV-16 E5 on the cell cycle progression during EGF-stimulation. Wild-type and NIH 3T3 cells over-expressing human EGF-receptor were transfected with HPV-16 E5 gene and the cell cycle progression was characterized. This analysis showed that the E5-expressing cells increased DNA synthesis (S-phase) by around 40%. Cell cycle protein analysis of E5-expressing cells showed a reduction in the half-life of p27(Kip1) protein as compared to control cells (18.4 vs. 12.7 h), an effect that was enhanced in EGF-stimulated cells (12.8 vs. 3.6 h). Blockage of EGF-receptor activity abrogated E5 signals as well as p27(Kip1) down-regulation. These results suggest that E5 and the EGF-receptor cooperate to enhance cell cycle entry and progression through regulating p27(Kip1) expression at protein level.
Adolfo Pedroza-Saavedra; Eric W-F Lam; Fernando Esquivel-Guadarrama; Lourdes Gutierrez-Xicotencatl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-07
Journal Detail:
Title:  Virology     Volume:  400     ISSN:  1096-0341     ISO Abbreviation:  Virology     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44-52     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Center for Research on Infectious Diseases, National Institute of Public Health, Cuernavaca, Morelos 62100, Mexico.
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MeSH Terms
Base Sequence
Cell Cycle / physiology
Cyclin-Dependent Kinase Inhibitor p27 / genetics*,  physiology
DNA Primers / genetics
Genes, Viral
Host-Pathogen Interactions / genetics,  physiology
Human papillomavirus 16 / genetics,  pathogenicity*,  physiology*
NIH 3T3 Cells
Oncogene Proteins, Viral / genetics,  physiology*
Receptor, Epidermal Growth Factor / genetics,  physiology*
Recombinant Proteins / genetics,  metabolism
Signal Transduction / physiology
Reg. No./Substance:
0/Cdkn1b protein, mouse; 0/DNA Primers; 0/Oncogene Proteins, Viral; 0/Recombinant Proteins; 0/oncogene protein E5, Human papillomavirus type 16; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC, Epidermal Growth Factor

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