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Article Dans Une Revue Journal of Cell Biology Année : 2009

Caspase-2 activation in the absence of PIDDosome formation

Résumé

PIDD (p53-induced protein with a death domain [DD]), together with the bipartite adapter protein RAIDD (receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a DD), is implicated in the activation of pro–caspase-2 in a high molecular weight complex called the PIDDosome during apoptosis induction after DNA damage. To investigate the role of PIDD in cell death initiation, we generated PIDD-deficient mice. Processing of caspase-2 is readily detected in the absence of PIDDosome formation in primary lymphocytes. Although caspase-2 processing is delayed in simian virus 40–immortalized pidd−/− mouse embryonic fibroblasts, it still depends on loss of mitochondrial integrity and effector caspase activation. Consistently, apoptosis occurs normally in all cell types analyzed, suggesting alternative biological roles for caspase-2 after DNA damage. Because loss of either PIDD or its adapter molecule RAIDD did not affect subcellular localization, nuclear translocation, or caspase-2 activation in high molecular weight complexes, we suggest that at least one alternative PIDDosome-independent mechanism of caspase-2 activation exists in mammals in response to DNA damage.
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Dates et versions

hal-02088184 , version 1 (02-04-2019)

Identifiants

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Claudia Manzl, Gerhard Krumschnabel, Florian Bock, Bénédicte Sohm, Verena Labi, et al.. Caspase-2 activation in the absence of PIDDosome formation. Journal of Cell Biology, 2009, 185 (2), pp.291-303. ⟨10.1083/jcb.200811105⟩. ⟨hal-02088184⟩
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