Suzuki A, Tsutomi Y, Miura M, Akahane K
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center 16-13, Japan.
Oncogene. 1999 Feb 4;18(5):1239-44. doi: 10.1038/sj.onc.1202409.
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.
死亡介质半胱天冬酶在细胞死亡诱导过程中起主要调节作用。包括半胱天冬酶3（CPP32/Yama/Apopain）在内的CPP32亚家族对细胞死亡信号传导至关重要。我们最近报道，半胱天冬酶3的激活受与p21或ILP形成复合物的调节。在本研究中，我们研究了与p21和ILP的结合结构域，以进一步表征半胱天冬酶3失活机制。我们的结果表明，半胱天冬酶3在N端含有p21结合结构域，在活性位点含有ILP结合结构域。此外，p21中的半胱天冬酶3结合结构域独立于Cdk或PCNA结合结构域。我们还发现p21对半胱天冬酶3的保护作用可防止p3位点切割丝氨酸蛋白酶的作用，这有助于抑制机制。在此，我们提出p21和ILP对半胱天冬酶3的失活系统是细胞死亡调节中的新的重要系统。
