Direct inhibition of caspase 3 is dispensable for the anti-apoptotic activity of XIAP
Details
Publication Year 2001-06-15, Volume 20, Issue #12, Page 3114-3123
Journal Title
EMBO JOURNAL
Publication Type
Journal Article
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 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.
Publisher
OXFORD UNIV PRESS
Keywords
CELL-DEATH; PROTEIN XIAP; SIGNALING COMPLEX; BACULOVIRUS IAP; MAMMALIAN-CELLS; NMR STRUCTURE; BIR DOMAIN; IN-VIVO; FAMILY; GENES
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2001-06-15 12:00:00
Last Modified: 0001-01-01 12:00:00
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