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

Oncogene volume 18, pages 1239–1244 (1999)Cite this article

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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Authors and Affiliations

  1. Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center 16-13, Kitakasai-1, Edogawa-ku, Tokyo, 134, Japan

    Atsushi Suzuki & Yumi Tsutomi

  2. Department of Neuroanatomy, Biomedical Research Center, Osaka University Medical School, Yamadaoka 2-2, Suita, Osaka, 565, Japan

    Masayuki Miura

  3. New Product Research Laboratory IV, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center 16-13, Kitakasai-1, Edogawa-ku, Tokyo, 134, Japan

    Kouichi Akahane

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  1. Atsushi Suzuki
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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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