The human papillomavirus E7 oncoprotein and the cellular transcription factor E2F bind to separate sites on the retinoblastoma tumor suppressor protein.
The ability of the high-risk and low-risk human papillomavirus E7 oncoproteins to disrupt complexes of the retinoblastoma tumor suppressor protein pRB and the cellular transcription factor E2F was studied. The ability of E7 to disrupt this transcription factor complex correlated with the different pRB binding efficiencies of the high-risk and low-risk human papillomavirus-encoded E7 proteins. The pRB binding site was the sole determinant for these observed differences. The phosphorylation status of the casein kinase II site that is immediately adjacent to the pRB binding site in E7 had no marked effect on this biochemical property of E7. Peptides consisting of the pRB binding site of E7, however, were not able to disrupt the pRB/E2F complex. These data suggest that additional carboxy-terminal sequences in E7 are also required for the efficient disruption of the pRB/E2F complex and that E7 and E2F may interact with nonidentical sites of pRB.
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Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Clemens
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Heck
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Münger
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D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16