Complementation of a p300/CBP defective-binding mutant of adenovirus E1a by human papillomavirus E6 proteins.
Previous studies have shown that the human papillomavirus type 16 (HPV-16) E6 protein binds to p300/CBP and abrogates its transcriptional co-activator function. However, there is little information on the biological consequences of this interaction and discrepancy as to whether the interaction is high-risk E6 specific or not. We performed a series of studies to compare the interactions of HPV-18 and HPV-11 E6 with p300, and showed that both high- and low- risk E6 proteins bind p300. In addition, using a transformation-deficient mutant of adenovirus E1a, which cannot interact with p300, we demonstrated that HPV-16, HPV-18 and, to a lesser extent, HPV-11 E6, can complement this mutant in cell transformation assays. In contrast, a mutant of HPV-16 E6 which does not bind p300 failed to rescue the E1a mutant. These results suggest that the E6-p300 interaction may be important for the ability of HPV E6 to contribute towards cell transformation.
Bernat
Agnieszka
A
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy1.
Massimi
Paola
P
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy1.
Banks
Lawrence
L
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy1.
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D002417:Cattle; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D012097:Repressor Proteins; D015534:Trans-Activators / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53