Ectopic expression of the serine protease inhibitor PI9 modulates death receptor-mediated apoptosis.

Apoptosis is a highly controlled process, whose triggering is associated with the activation of caspases. Apoptosis can be induced via a subgroup of the tumor necrosis factor (TNF) receptor superfamily, which recruit and activate pro-caspase-8 and -10. Regulation of apoptosis is achieved by several inhibitors, including c-FLICE-inhibitory protein, which prevents ...
apoptosis by inhibiting the pro-apoptotic activation of upstream caspases. Here we show that the human intracellular serine protease inhibitor (serpin), protease inhibitor 9 (PI9), inhibits TNF-, TNF-related apoptosis-inducing ligand- and Fas ligand-mediated apoptosis in certain TNF-sensitive cell lines. The reactive center P1 residue of PI9 was required for this inhibition since PI9 harboring a Glu --> Ala mutation in its reactive center failed to impair death receptor-induced cell death. This suggests a classical serpin-protease interaction. Indeed, PI9 inhibited apoptotic death by directly interacting with the intermediate active forms of caspase-8 and -10. This indicates that PI9 can regulate pro-apoptotic apical caspases.
Mesh Terms:
Animals, Apoptosis, Caspase 10, Caspase 3, Caspase 8, Cell Line, Tumor, Fas Ligand Protein, Humans, Ligands, Mice, Models, Biological, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases, Protein Processing, Post-Translational, Receptors, Death Domain, Recombinant Proteins, Serine Proteinase Inhibitors, Serpins, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand, Transduction, Genetic, Tumor Necrosis Factor-alpha
Cell Death Differ.
Date: Aug. 01, 2007
Download Curated Data For This Publication
206777
Switch View:
  • Interactions 2