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.