Caspase-2 activation in the absence of PIDDosome formation.

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Serval ID
serval:BIB_ED9C5C0DC6DE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Caspase-2 activation in the absence of PIDDosome formation.
Journal
The Journal of cell biology
Author(s)
Manzl C., Krumschnabel G., Bock F., Sohm B., Labi V., Baumgartner F., Logette E., Tschopp J., Villunger A.
ISSN
1540-8140[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
185
Number
2
Pages
291-303
Language
english
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
03/12/2009 9:25
Last modification date
20/08/2019 16:15
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