Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21

被引:131
作者
Suzuki, A
Tsutomi, Y
Miura, M
Akahane, K
机构
[1] Daiichi Pharmaceut Co Ltd, Drug Safety Res Lab, Tokyo R&D Ctr, Edogawa Ku, Tokyo 134, Japan
[2] Osaka Univ, Sch Med, Dept Neuroanat, Ctr Biomed Res, Suita, Osaka 565, Japan
[3] Daiichi Pharmaceut Co Ltd, New Prod Res Lab 4, Tokyo R&D Ctr, Edogawa Ku, Tokyo 134, Japan
关键词
Fas; caspase; 3; p21; ILP; serineproteinase;
D O I
10.1038/sj.onc.1202409
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
The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling, We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP, In the present study, we investigated the binding domain with p21 and ILP to further characterize the caspase 3 inactivation machinery, Our results show that caspase 3 contains p21 binding domain in the N-terminus and ILP binding domain in the active site, Further, the caspase 3 binding domain in p21 was independent of the Cdk- or PCNA-binding domain. We also found caspase 3 protection by p21 from the p3-site cleavage serineproteinase contributes to the suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death.
引用
收藏
页码:1239 / 1244
页数:6
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