Article: article from journal or magazin.
Caspase-2 activation in the absence of PIDDosome formation.
The Journal of cell biology
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.
Animals, Apoptosis/physiology, CRADD Signaling Adaptor Protein/genetics, CRADD Signaling Adaptor Protein/metabolism, Carrier Proteins/genetics, Carrier Proteins/metabolism, Caspase 2/genetics, Caspase 2/metabolism, Cells, Cultured, Cytochromes c/metabolism, DNA Damage, Enzyme Activation, Female, Fibroblasts/cytology, Fibroblasts/physiology, Gamma Rays, Humans, Lymphocytes/cytology, Lymphocytes/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria/metabolism, Multiprotein Complexes/chemistry, Multiprotein Complexes/metabolism, Protein Precursors/genetics, Protein Precursors/metabolism
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