Caspase-2 activation in the absence of PIDDosome formation.
Details
Download: BIB_ED9C5C0DC6DE.P001.pdf (3614.41 [Ko])
State: Public
Version: author
State: Public
Version: author
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
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