HPV-18 E6 inhibits p53 DNA binding activity regardless of the oligomeric state of p53 or the exact p53 recognition sequence.
The E6 proteins of the oncogenic-associated human papillomavirus types 16 (HPV-16) and 18 (HPV-18) function by interfering with the normal cell cycle control mechanisms, particularly those controlled by p53. HPV E6 is able to interfere with p53 function by preventing its binding to DNA target sequences and also by labelling p53 for ubiquitin-mediated degradation. We have previously reported that certain p53 mutants, defective in oligomerisation, vary in their susceptibility to E6-directed labelling for ubiquitin-mediated degradation. In this paper we report that the strength of p53's binding to DNA is dependent upon the precise target sequence, but that E6 is able to disrupt each complex. We also report the binding of different oligomeric forms of p53 to different DNA sequences and correlate this with in vivo transcriptional activity and demonstrate the susceptibility of that DNA binding to disruption by E6. Finally we show that the ability of p53 to bind to TBP is a function of its oligomeric state and correlates in part with its ability to transrepress but not with its ability to transactivate.
Thomas
M
M
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Massimi
P
P
Banks
L
L
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D013329:Structure-Activity Relationship; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA