Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [37 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00144897
Contributor : Olivier Micheau <>
Submitted on : Monday, November 5, 2007 - 2:10:54 PM
Last modification on : Thursday, February 7, 2019 - 4:42:15 PM
Long-term archiving on: : Wednesday, April 7, 2010 - 2:14:05 AM

Identifiers

Collections

Citation

Jean Kummer, Olivier Micheau, Pascal Schneider, Niels Bovenschen, Roel Broekhuizen, et al.. Ectopic expression of the serine protease inhibitor PI9 modulates death receptor-mediated apoptosis.. Cell Death and Differentiation, Nature Publishing Group, 2007, 14 (8), pp.1486-96. ⟨10.1038/sj.cdd.4402152⟩. ⟨inserm-00144897⟩

Share

Metrics

Record views

289

Files downloads

901