Journal article

Direct inhibition of caspase 3 is dispensable for the anti-apoptotic activity of XIAP

J Silke, PG Ekert, CL Day, CJ Hawkins, M Baca, J Chew, M Pakusch, AM Verhagen, DL Vaux

EMBO JOURNAL | WILEY | Published : 2001

Abstract

XIAP is a mammalian inhibitor of apoptosis protein (IAP). To determine residues within the second baculoviral IAP repeat (BIR2) required for inhibition of caspase 3, we screened a library of BIR2 mutants for loss of the ability to inhibit caspase 3 toxicity in the yeast Schizosaccharomyces pombe. Four of the mutations, not predicted to affect the structure of the BIR fold, clustered together on the N-terminal region that flanks BIR2, suggesting that this is a site of interaction with caspase 3. Introduction of these mutations into full-length XIAP reduced caspase 3 inhibitory activity up to 500-fold, but did not affect its ability to inhibit caspase 9 or interact with the IAP antagonist DIAB..

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University of Melbourne Researchers