Suppression of interleukin-1beta converting enzyme (ICE)-induced apoptosis by SV40 large T antigen.
The Interleukin-1beta 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-1(L). 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-1(L)-mediated cell death. Thus, wild type p53 may potentiate ICE-induced apoptosis. Expression of a temperature sensitive mutant p53Val(135) sensitizes COS-1 cells to apoptosis induced by ICE at permissive but not at non-permissive temperature. While induction of bax, p21(WAF1/CIP), or cyclin D1 gene expression is observed in the COS-1 p53Val(135) cells at the permissive temperature, overexpression of bax, but not p21(WAF1/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.
Jung
Y K
YK
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Yuan
J
J
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D006801:Humans; D015513:Oncogene Proteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D015843:Serpins / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein
D000952:Antigens, Polyomavirus Transforming; C494826:BAX protein, human; C494828:Bax protein, rat; C493956:CDKN1A protein, human; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015843:Serpins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; C074641:interleukin-1beta-converting enzyme inhibitor