Suppression of Interleukin-1β converting enzyme (ICE)-induced apoptosis by SV40 large T antigen

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Abstract
The Interleukin-1β converting enzyme (ICE) family of proteins, homologs of the C elegans cell death gene product CED-3, play important roles in controlling vertebrate programmed cell death. Because inhibition of apoptosis may be an essential step in tumorigenesis, we investigated the interaction of the simian virus 40 large T antigen (T ag) with the ICE family. COS-1 cells which were transformed by the simian virus 40 do not die when transfected with expression constructs of Ice or Ich-1L. We found that expression of T ag alone significantly prevents the ICE-induced apoptosis. p53, but not pRb or p107, antagonizes the effect of T ag on the suppression of ICE-induced cell death, but not on ICH-1L-mediated cell death. Thus, wild type p53 may potentiate ICE-induced apoptosis. Expression of a temperature sensitive mutant p53Val135 sensitizes COS-1 cells to apoptosis induced by ICE at permissive but not at non-permissive temperature. While induction of bax, p21WAF1/CIP, or cyclin D1 gene expression is observed in the COS-1 p53Val135 cells at the permissive temperature, overexpression of bax, but not p21WAF1/CIP or cyclin D1, potentiates ICE-induced COS-1 cell death. Taken together, these results suggest that T ag may modulate the cells' susceptibility to death by suppressing activity of the ICE family through inhibiting p53.

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