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Cells expressing HPV16 E7 continue cell cycle progression following DNA damage induced p53 activation
E S Hickman1, S M Picksley, K H Vousden
1Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, London, UK.
Oncogene
|August 1, 1994
Summary
Human papillomavirus oncoproteins E6 and E7 enable cell cycle progression after DNA damage. E6 targets p53 for degradation, while E7 interacts with pRB, suggesting a shared pathway in cell cycle regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Virology
Background:
- p53 stabilization and activation induce G1 cell cycle arrest in response to DNA damage.
- p53 transcriptional activity includes upregulating inhibitors of cyclin-dependent kinases.
- Cyclin-dependent kinases inactivate the growth-inhibitory function of the pRB tumor suppressor protein.
Purpose of the Study:
- To investigate the role of human papillomavirus (HPV) oncoproteins E6 and E7 in cell cycle regulation following DNA damage.
- To determine if HPV E6 and E7 oncoproteins can override DNA damage-induced cell cycle arrest.
Main Methods:
- Cell-based assays to assess cell cycle progression.
- Analysis of p53 and pRB protein levels and interactions.
- Expression of HPV E6 and E7 oncoproteins in human cells.
Main Results:
- Expression of HPV E6 or E7 oncoproteins permitted cell cycle progression despite DNA damage.
- HPV E6 oncoprotein targets p53 for degradation.
- HPV E7 oncoprotein interacts with pRB, a downstream effector of p53.
Conclusions:
- Both HPV E6 and E7 oncoproteins contribute to the disruption of cell cycle control after DNA damage.
- HPV E6 and E7 likely function in the same pathway to promote uncontrolled cell proliferation.
- These findings elucidate a mechanism by which HPV promotes oncogenesis.