Inhibition of ICE Family Proteases by Baculovirus Antiapoptotic Protein p35

• DOI: 10.1126/science.7569933
• Publication Date: 2006-10-27T18:19:42Z
• Authors: Nancy J. Bump; Maria Hackett; Margaret Hugunin; Somasekar Seshagiri; Kenneth Brady; Patrick Chen; Catherine Ferenz; Simon Franklin; Tariq Ghayur; Ping Li; Peter Licari; John Mankovich; Lianfa Shi; Arnold H. Greenberg; Lois K. Miller; Winnie W. Wong
• Keywords: 0301 basic medicine; Binding Sites; Caspase 1; Molecular Sequence Data; Apoptosis; Cysteine Proteinase Inhibitors; Transfection; Binding, Competitive; Recombinant Proteins; Cell Line; Inhibitor of Apoptosis Proteins; Enzyme Activation; Cysteine Endopeptidases; Viral Proteins; 03 medical and health sciences; Animals; Humans; Amino Acid Sequence

The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1β converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.