Apoptosis Is Induced at Nonpermissive Temperature by a Transient Increase in p53 in Cell Lines Immortalized with Temperature-Sensitive SV40 Large T-Antigen Gene

Abstract

Hepatocyte (TLR2) and kidney tubule (TKC2) cell lines established from temperature-sensitive (ts) SV40 T-antigen gene transgenic mice not only were arrested in growth, but also exhibited cell death at nonpermissive temperature (39°C). The cell death was determined to be caused by apoptosis from observations of nuclear fragmentation and DNA fragmentation. These cell lines contained relatively high levels of wild-type p53 which formed complexes with T-antigen at permissive temperature (33°C), but after shift to a nonpermissive temperature, the inactivation of T-antigens led to the liberation of an abundance of p53 proteins from the complexes, apparently inducing apoptosis.