Caspase 8-mediated cleavage of the pro-apoptotic BCL-2 family member BID in p53-dependent apoptosis |
| |
Authors: | Fischer Barbara Coelho David Dufour Patrick Bergerat Jean Pierre Denis Jean Marc Gueulette John Bischoff Pierre |
| |
Affiliation: | a Laboratoire de Cancérologie Expérimentale et de Radiobiologie EA 3430, Université Louis Pasteur, Institut de Recherche contre les Cancers de l’Appareil Digestif, Strasbourg, France b Laboratoire de Radiobiologie et de Radioprotection, Faculté de Médecine, Université Catholique de Louvain, Brussels, Belgium |
| |
Abstract: | The objective of this study was to characterize the apoptotic pathways activated by fast neutrons in the human lymphoblastoid cell line TK6 and in its p53 −/− derivative. Our results demonstrate that while p53 is not required for neutron-induced apoptosis, as previously shown, it does affect the kinetics of apoptosis and the molecular pathways leading to the activation of effector caspases. Indeed, rapid p53-dependent apoptosis was associated with the activation of caspase 9, 8, 3, and 7 and the cleavage of BID by caspase 8. In contrast, the slow-occurring p53-independent apoptotic process, mediated by caspase 7, took place without BID cleavage and loss of transmembrane mitochondrial potential. Altogether, our findings highlight an essential role for caspase 8-mediated BID cleavage, in the course of p53-dependent apoptosis triggered by fast neutrons in lymphoid cells. They also demonstrate that this mechanism is not involved in p53-independent apoptosis. |
| |
Keywords: | Bid p53 Apoptosis Caspases Mitochondria Transduction pathways Fast neutrons |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|