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  • Original Paper
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Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death

Abstract

Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.

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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, and Dr H Matsushime for pGST-p21. The preparation of this manuscript was supported by the Idest Inc., Edmond, OK, USA.

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Suzuki, A., Ito, T., Kawano, H. et al. Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene 19, 1346–1353 (2000). https://doi.org/10.1038/sj.onc.1203429

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