| First Author | Manzl C | Year | 2009 |
| Journal | J Cell Biol | Volume | 185 |
| Issue | 2 | Pages | 291-303 |
| PubMed ID | 19364921 | Mgi Jnum | J:148929 |
| Mgi Id | MGI:3847154 | Doi | 10.1083/jcb.200811105 |
| Citation | Manzl C, et al. (2009) Caspase-2 activation in the absence of PIDDosome formation. J Cell Biol 185(2):291-303 |
| abstractText | 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. |
