Caspase-3 protects stressed organs against cell death

Hadi Khalil, Nieves Peltzer, Joël Walicki, Jiang Yan Yang, Gilles Dubuis, Noémie Gardiol, Werner Held, Paul Bigliardi, Benjamin Marsland, Lucas Liaudet, Christian Widmann

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


The ability to generate appropriate defense responses is crucial for the survival of an organism exposed to pathogenesis-inducing insults. However, the mechanisms that allow tissues and organs to cope with such stresses are poorly understood. Here we show that caspase-3-knockout mice or caspase inhibitor-treated mice were defective in activating the antiapoptotic Akt kinase in response to various chemical and environmental stresses causing sunburns, cardiomyopathy, or colitis. Defective Akt activation in caspase-3-knockout mice was accompanied by increased cell death and impaired survival in some cases. Mice homozygous for a mutation in RasGAP that prevents its cleavage by caspase-3 exhibited a similar defect in Akt activation, leading to increased apoptosis in stressed organs, marked deterioration of their physiological functions, and stronger disease development. Our results provide evidence for the relevance of caspase-3 as a stress intensity sensor that controls cell fate by either initiating a RasGAP cleavage-dependent cell resistance program or a cell suicide response.

Original languageEnglish (US)
Pages (from-to)4523-4533
Number of pages11
JournalMolecular and cellular biology
Issue number22
StatePublished - Nov 2012


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