title: The tumor-modulatory effects of Caspase-2 and Pidd1 do not require the scaffold protein Raidd.
abstract: The receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a death domain (RAIDD/CRADD) functions as a dual adaptor and is a constituent of different multi-protein complexes implicated in the regulation of inflammation and cell death. Within the PIDDosome complex, RAIDD connects the cell death-related protease, Caspase-2, with the p53-induced protein with a death domain 1 (PIDD1). As such, RAIDD has been implicated in DNA-damage-induced apoptosis as well as in tumorigenesis. As loss of Caspase-2 leads to an acceleration of tumor onset in the Eμ-Myc mouse lymphoma model, whereas loss of Pidd1 actually delays onset of this disease, we set out to interrogate the role of Raidd in cancer in more detail. Our data obtained analyzing Eμ-Myc/Raidd(-/-) mice indicate that Raidd is unable to protect from c-Myc-driven lymphomagenesis. Similarly, we failed to observe a modulatory effect of Raidd deficiency on DNA-damage-driven cancer. The role of Caspase-2 as a tumor suppressor and that of Pidd1 as a tumor promoter can therefore be uncoupled from their ability to interact with the Raidd scaffold, pointing toward the existence of alternative signaling modules engaging these two proteins in this context.
authors: Division of Developmental Immunology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
authors: L
authors: L
authors: Peintner
authors: Centre for Cancer Biology - An Alliance between SA Pathology and the University of South Australia, Adelaide, SA 5001, Australia.
authors: L
authors: L
authors: Dorstyn
authors: Centre for Cancer Biology - An Alliance between SA Pathology and the University of South Australia, Adelaide, SA 5001, Australia.
authors: S
authors: S
authors: Kumar
authors: Division of Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria.
authors: T
authors: T
authors: Aneichyk
authors: Division of Developmental Immunology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
authors: A
authors: A
authors: Villunger
authors: Division of Developmental Immunology, Medical University of Innsbruck, 6020 Innsbruck, Austria.|Department of General Pathology, Medical University of Innsbruck, Innsbruck 6020, Austria.
authors: C
authors: C
authors: Manzl
mesh_terms: D000818:Animals; D053420:CRADD Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
chemical_list: D053420:CRADD Signaling Adaptor Protein; C484481:Cradd protein, mouse; D053418:Death Domain Receptor Signaling Adaptor Proteins; C414729:Pidd1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D053143:Caspase 2