Abstract
Caspase 3 is an essential factor for Fas-mediated cell death and exists endogenously in cells where its activation is suppressed by p21 and ILP. Inside the cell, procaspase 3 interacts with p21 on mitochondria. In the present study, we investigated the molecular basis for procaspase 3/p21 complex formation. During Fas-mediated cell death, mitochondria are damaged, accompanied by decreased mitochondrial membrane-potential and decreased intracellular ATP levels. This mitochondrial damage occurs before an estrangement of the procaspase 3/p21 complex, and we demonstrate that intracellular ATP-deprivation also initiates an estrangement of procaspase 3/p21 complex formation and accelerates Fas-mediated cell death. In addition, our current results revealed that the phosphorylated p21 by PKA interacts with procaspase 3. Here, we report that the mitochondrial role, especially for ATP synthesis, and PKA are necessary for the procaspase 3/p21 complex formation to resist Fas-mediated cell death. Cell Death and Differentiation (2000) 7, 721–728
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Abbreviations
- adenosine triphosphate:
-
ATP
- protein kinase A:
-
PKA
- agonistic anti-human Fas antibody CH-11 clone:
-
Fas Ab
- 5′-p-fluorosulfonylbenzoyl adenosine:
-
FSBA
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Acknowledgements
We thank Dr. Yoshihide Tsujimoto, Osaka University Medical School, for human hepatoma HepG2 cells, and Dr. Masayuki Miura, Osaka University of Medical School, for his valuable discussions. The preparation of this manuscript was supported by the Idest Inc., Edmond, OK, USA.
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Suzuki, A., Kawano, H., Hayashida, M. et al. Procaspase 3/p21 complex formation to resist Fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A. Cell Death Differ 7, 721–728 (2000). https://doi.org/10.1038/sj.cdd.4400706
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DOI: https://doi.org/10.1038/sj.cdd.4400706
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