Analysis of candidate antagonists of IAP-mediated caspase inhibition using yeast reconstituted with the mammalian Apaf-1-activated apoptosis mechanism

被引：32
作者：
Hawkins, CJ
Silke, J
Verhagen, AM
Foster, R
Ekert, PG
Ashley, DM
机构：
[1] Royal Childrens Hosp, Dept Haematol & Oncol, Parkville, Vic 3052, Australia
[2] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia
[3] Royal Childrens Hosp, Dept Neonatol, Parkville, Vic 3052, Australia
[4] Univ Melbourne, Dept Paediat, Parkville, Vic 3010, Australia
[5] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, PO Royal Melbourne Hosp, Parkville, Vic 3050, Australia
来源：
APOPTOSIS | 2001年 / 6卷 / 05期
基金：
澳大利亚研究理事会;
关键词：
caspase; IAP; apoptosis; yeast; Drosophila; S; cerevisiae;
D O I：
10.1023/A:1011329917895
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We have reconstituted the Apaf-1-activated apoptosis mechanism in Sacchromyces cerevisiae such that the presence of a constitutively active form of Apaf-1 together with both Caspase-9 and Caspase-3 results in yeast death. This system is a good model of the Apaf-1-activated pathway in mammalian cells: MIHA (XIAP/hILP), and to a lesser degree MIHB (c-IAP1/HIAP2) and MIHC (c-IAP-2/HIAP1) can inhibit caspases in this system, and protection by IAPs (inhibitor of apoptosis) can be abrogated by coexpression of the Drosophila pro-apoptotic proteins HID and GRIM or the mammalian protein DIABLO/Smac. Using this system we demonstrate that unlike DIABLO/Smac, other proteins which interact with mammalian IAPs (TAB-1, Zap-1, Traf-1 and Traf-2) do not act to antagonise IAP- mediated caspase inhibition.
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页码：331 / 338
页数：8
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