Premium
Direct inhibition of caspase 3 is dispensable for the anti‐apoptotic activity of XIAP
Author(s) -
Silke John,
Ekert Paul G.,
Day Catherine L.,
Hawkins Christine J.,
Baca Manuel,
Chew Joanne,
Pakusch Miha,
Verhagen Anne M.,
Vaux David L.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.12.3114
Subject(s) - xiap , biology , caspase , apoptosis , caspase 3 , microbiology and biotechnology , caspase 9 , caspase 8 , caspase 2 , cancer research , genetics , programmed cell death
XIAP is a mammalian i nhibitor of a poptosis p rotein (IAP). To determine residues within the second b aculoviral I AP r epeat (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 DIABLO. Furthermore, these mutants retained full ability to inhibit apoptosis in transfected cells, demonstrating that although XIAP is able to inhibit caspase 3, this activity is dispensable for inhibition of apoptosis by XIAP in vivo .