Journal of Virology
Geisel School of Medicine
The ability of DNA tumor virus proteins to trigger apoptosis in mammalian cells is well established. For example, transgenic expression of a simian virus 40 (SV40) T-antigen N-terminal fragment (N-termTag) is known to induce apoptosis in choroid plexus epithelial cells. SV40 T-antigen-induced apoptosis has generally been considered to be a p53-dependent event because cell death in the brain is greatly diminished in a p53-/- background strain and is abrogated by expression of wild-type (p53-binding) SV40 T antigen. We now show that while N-termTags triggered apoptosis in rat embryo fibroblasts cultured in low serum, expression of full-length T antigens unable to bind p53 [mut(p53-)Tags] protected against apoptosis without causing transformation. One domain essential for blocking apoptosis by T antigen was mapped to amino acids 525 to 541. This domain has >60% homology with a domain of adenovirus type 5 E1B 19K required to prevent E1A-induced apoptosis. In the context of both wild-type T antigen and mut(p53-)Tags, mutation of two conserved amino acids in this region eliminated T antigen's antiapoptotic activity in REF-52 cells. These data suggest that SV40 T antigen contains a novel functional domain involved in preventing apoptosis independently of inactivation of p53.
Conzen SD, Snay CA, Cole CN. Identification of a novel antiapoptotic functional domain in simian virus 40 large T antigen. J Virol. 1997;71(6):4536-4543. doi:10.1128/JVI.71.6.4536-4543.1997
Dartmouth Digital Commons Citation
Conzen, Suzanne D.; Snay, Christine A.; and Cole, Charles N., "Identification of a Novel Antiapoptotic Functional Domain in Simian Virus 40 Large T Antigen." (1997). Dartmouth Scholarship. 1142.