Human papillomavirus type 16 E7 binds to the conserved carboxy-terminal region of the TATA box binding protein and this contributes to E7 transforming activity.
We have previously shown that the human papillomavirus E7 proteins bind to the cellular TATA box binding protein (TBP). In this paper we show that the HPV-18 E6 and the HPV-16 E2 proteins will also bind TBP in vitro. This feature of virus proteins is conserved across many viral types and we were interested in determining whether these HPV proteins interacted with the same conserved region of the TBP molecule. A series of deletions was introduced into the TBP protein and its binding to these HPV proteins was measured. The previously well-characterized interaction between p53 and TBP was used for comparison. All four proteins were found to interact with the carboxy-terminal domain of the TBP protein, although the precise residues involved and the relative strengths of association differed between the different HPV proteins. Mutational analysis of HPV-16 E7 protein identified a stretch of four amino acids responsible for the binding to TBP. This mutant E7 protein possessed wild-type levels of transcriptional activity on the adenovirus E2 promoter but exhibited reduced transforming activity in cooperation with EJ-ras. These results demonstrate that the mechanisms of interaction between diverse viral proteins and TBP are similar and that, in the case of E7, this interaction may contribute to its transforming activity.
Massimi
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International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Pim
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Banks
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D000818:Animals; D001665:Binding Sites; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; C059731:oncogene protein E7, Human papillomavirus type 16