Loss of Caspase-9 Provides Genetic Evidence for the Type I/II Concept of CD95-mediated Apoptosis
| Autor: | Nana Ueffing, Ingo Schmitz, Ajoy K. Samraj, Eric Keil, Klaus Schulze-Osthoff |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Necrosis
T cell Action Potentials Apoptosis Mitochondrion Biochemistry Permeability Jurkat Cells Mice Cell Line Tumor medicine Animals Humans fas Receptor Molecular Biology Caspase Caspase-9 biology Cytochrome c Cell Biology Fas receptor Caspase 9 Cell biology medicine.anatomical_structure Mitochondrial Membranes biology.protein medicine.symptom |
| Zdroj: | Journal of Biological Chemistry. 281:29652-29659 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m603487200 |
| Popis: | The death receptor CD95 triggers apoptosis upon formation of a death-inducing signaling complex and the activation of caspase-8. Two types of CD95-mediated apoptosis have been distinguished that differ in their efficiency of death-inducing signaling complex formation and the requirement of mitochondria for caspase activation. The validity of the type I/II model, however, has been challenged, as Bcl-2 expression or the use of various CD95 agonists resulted in different apoptosis effects. By identifying a caspase-9-deficient T cell line, we now provide genetic evidence for the two-pathway model of CD95-mediated apoptosis and demonstrate that type II cells strongly depend on caspase-9. Caspase-9-deficient cells revealed strongly impaired apoptosis, caspase activation, and mitochondrial membrane depolarization upon CD95 triggering, whereas, surprisingly, activation of Bak and cytochrome c release were not inhibited. Furthermore, caspase-9-deficient cells did not switch to necrosis, and reconstitution of caspase-9 expression restored CD95 sensitivity. Finally, we also show that different death receptors have a distinct requirement for caspase-9. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|