HPV-16 E7 or adenovirus E1A can overcome the growth arrest of cells immortalized with a temperature-sensitive p53.
Rat embryo fibroblasts immortalized with a temperature-sensitive p53 mutant and ras rapidly stop proliferating at 33 degrees C. Expression of the viral oncoproteins human papillomavirus type 16 (HPV-16) E7 or adenovirus E1A efficiently overcame this growth arrest, although cells rescued by E7 or E1A displayed no detectable changes in p53 expression. Co-transfection of HPV-16 E6, which binds and directs the degradation of human p53, affected neither growth of the cells at 33 degrees C nor the amount or conformation of the p53 protein, possibly reflecting an inability of E6 to interact with mouse p53 in rodent cells. Our results suggest either that the temperature-sensitive p53 failed to regain full wild-type suppressor activity at 33 degrees C or that E7 and E1A can modulate wild-type p53 growth-suppressor activity without altering the conformation or stability of the protein.
Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, London, UK.
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Vousden
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Vojtesek
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Fisher
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Lane
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002461:Cell Line, Transformed; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D010957:Plasmids; D051381:Rats; D012097:Repressor Proteins; D013696:Temperature; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16