Abstract
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.
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Acknowledgements
We thank Dr Y Tsujimoto for human hepatoma HepG2 cells, Dr CB Thompson for the ILP cDNA, Dr HR Horvitz for the pET21b-hcpp32-His6 clone plasmid, Dr H Matsushime for pGST-p21 and Dr M Furusawa for his valuable discussion.
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Suzuki, A., Tsutomi, Y., Miura, M. et al. Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21. Oncogene 18, 1239–1244 (1999). https://doi.org/10.1038/sj.onc.1202409
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DOI: https://doi.org/10.1038/sj.onc.1202409
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