Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21
Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21
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DOI：
10.1038/sj.onc.1202409
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发表时间：
1999-02-04
期刊：
影响因子：
8
通讯作者：
Akahane, K
中科院分区：
文献类型：
--
作者：
Suzuki, A;Tsutomi, Y;Akahane, K
死亡介质半胱天冬酶在细胞死亡诱导期间充当主导调节剂。CPP32亚家族，包括caspase 3（CPP32/Yama/Apopain），是细胞死亡信号的关键，我们最近报道了caspase 3的激活受p21或ILP复合物的形成的调节，在本研究中，我们研究了与p21和ILP的结合结构域，以进一步表征caspase 3的失活机制，结果表明，caspase 3在N端含有p21结合结构域，在活性部位含有ILP结合结构域，且p21的caspase 3结合结构域不依赖于Cdk或PCNA结合结构域。我们还发现，p21对caspase 3的保护作用，使其免受p3位点丝氨酸蛋白酶的切割，有助于抑制机制。在此，我们提出p21和ILP介导的caspase 3失活系统是调控细胞死亡的新的重要系统。
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.