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

Caspase 3 is an essential factor for Fas-mediated cell death and exists end ogenously in cells where its activation is suppressed by p21 and ILP. Insid e the cell, procaspase 3 interacts with p21 on mitochondria. In the present study, we investigated the molecular basis for procaspase 3/p21 complex fo rmation. During Fas-mediated cell death, mitochondria are dam aged, accompa nied by decreased mitochondrial membrane-potential and decreased intracellu lar ATP levels. This mitochondrial damage occurs before an estrangement of the procaspase 3/p21 complex, and we demonstrate that intracellular ATP-dep rivation also initiates an estrangement of procaspase 3/p21 complex formati on and accelerates Fas-mediated cell death. In addition, our current result s 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.