Cell cycle-dependent disruption of E2F-p107 complexes by human papillomavirus type 16 E7.
The human papillomavirus type 16 (HPV-16) E7 and adenovirus (Ad) E1A oncoproteins share a common pathway of transformation. They disrupt the cell cycle G1 phase-specific protein complex containing the E2F transcription factor and the regulatory protein Rb1, the retinoblastoma tumour suppressor gene product. In the G1 and S phases of the cell cycle, E7 and E1A bind two other cellular complexes containing the Rb1-related protein p107 and E2F. Ad E1A disrupts both complexes and releases active E2F. In contrast, HPV-16 E7, although it efficiently binds both E2F-p107 complexes, causes dissociation of the G1 phase complex only. Using chimeric proteins of HPV-16 E7 and Ad E1A we were able to demonstrate that the ability of E1A to disrupt both G1 and S phase E2F-p107 complexes is not due to the higher concentration of Ad E1A in the cell, but is an intrinsic property of the Ad E1A transforming region. These data suggest that E1A and E7 may function in cellular transformation in similar, but not identical ways.
Zerfass
K
K
Imperial Cancer Research Fund Tumour Virus Group, Department of Pathology, University of Cambridge, UK.
Levy
L M
LM
Cremonesi
C
C
Ciccolini
F
F
Jansen-Dürr
P
P
Crawford
L
L
Ralston
R
R
Tommasino
M
M
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C493844:RBL1 protein, human; C489485:Rbl1 protein, mouse; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050680:Transcription Factor DP1; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16