Identification of a novel antiapoptotic functional domain in simian virus 40 large T antigen

Suzanne D. Conzen, Christine A. Snay, Charles N. Cole

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4536-4543
Number of pages8
JournalJournal of virology
Volume71
Issue number6
DOIs
StatePublished - Jun 1997

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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