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

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 activa tion 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 furt her characterize the caspase 3 inactivation machinery, Our results show tha t caspase 3 contains p21 binding domain in the N-terminus and ILP binding d omain 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 pro tection by p21 from the p3-site cleavage serineproteinase contributes to th e suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death.