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J Cell Biol. 2009 Apr 20;185(2):291-303. doi: 10.1083/jcb.200811105. Epub 2009 Apr 13.

Caspase-2 activation in the absence of PIDDosome formation.

Author information

1
Division of Developmental Immunology, Biocenter, Innsbruck Medical University, A-6020 Innsbruck, Austria.

Abstract

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.

PMID:
19364921
PMCID:
PMC2700374
DOI:
10.1083/jcb.200811105
[Indexed for MEDLINE]
Free PMC Article

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