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Cell cycle-dependent disruption of E2F-p107 complexes by human papillomavirus type 16 E7
K Zerfass1, L M Levy, C Cremonesi
1Imperial Cancer Research Fund Tumour Virus Group, Department of Pathology, University of Cambridge, UK.
The Journal of General Virology
|July 1, 1995
Summary
Human papillomavirus type 16 (HPV-16) E7 and adenovirus (Ad) E1A oncoproteins disrupt cell cycle regulation. While both bind E2F-p107 complexes, Ad E1A disrupts both G1 and S phase complexes, unlike HPV-16 E7.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Human papillomavirus type 16 (HPV-16) E7 and adenovirus (Ad) E1A oncoproteins are key viral transforming proteins.
- Both oncoproteins target the retinoblastoma tumor suppressor protein (Rb1) and related proteins, disrupting cell cycle control.
Purpose of the Study:
- To compare the mechanisms by which HPV-16 E7 and Ad E1A disrupt cellular complexes containing Rb1-related proteins and E2F transcription factors.
- To elucidate the specific regions of Ad E1A responsible for its distinct activity.
Main Methods:
- Utilized chimeric proteins constructed from HPV-16 E7 and Ad E1A.
- Analyzed the disruption of G1 and S phase specific E2F-p107 complexes.
Main Results:
- HPV-16 E7 and Ad E1A bind to cellular complexes containing Rb1-related protein p107 and E2F.
- Ad E1A disrupts both G1 and S phase E2F-p107 complexes, releasing active E2F, while HPV-16 E7 primarily disrupts the G1 phase complex.
- Chimeric protein analysis revealed that the Ad E1A transforming region intrinsically confers the ability to disrupt both G1 and S phase complexes.
Conclusions:
- Ad E1A and HPV-16 E7 share common pathways in cellular transformation but exhibit distinct mechanisms in disrupting cell cycle regulatory complexes.
- The transforming region of Ad E1A possesses intrinsic properties enabling broader disruption of E2F-p107 complexes compared to HPV-16 E7.