{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nC13orf42, also known as CRADD (or RAIDD), functions as a critical adaptor protein in apoptotic signaling pathways. It participates in assembling multi‐protein complexes—such as the PIDDosome—where it bridges PIDD and caspase‐2 to mediate p53‐dependent cell death. In fibroblasts, this mechanism involves early activation of caspase‑2 followed by engagement of downstream caspases, while in neurons, CRADD facilitates caspase‑2 activation in response to stresses like NGF deprivation and β‑amyloid toxicity independently of PIDD. These findings underscore its central role in executing apoptotic programs in diverse cell types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its well‐established role in apoptosis, C13orf42/CRADD also influences cellular differentiation and immune signaling. Overexpression studies in preadipocytes reveal that increased CRADD levels hinder differentiation by blocking the induction of adipocyte-specific programs, suggesting a regulatory function in cell fate decisions. Furthermore, CRADD can interact with the caspase-recruitment domain of BCL10, thereby disrupting the formation of complexes such as the CARMA1 signalosome. This interference negatively regulates T cell receptor-triggered production of proinflammatory cytokines, highlighting a modulatory function in immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in vascular endothelial cells, CRADD emerges as an important anti-inflammatory mediator. Its presence restrains excessive BCL10-dependent signaling following inflammatory stimuli, thus maintaining endothelial barrier integrity by limiting the production of cytokines such as IL‑6 and MCP‑1 and reducing actin cytoskeleton remodeling. Loss of CRADD in these cells exacerbates permeability responses and inflammation, underscoring its role as a regulator that interconnects cell death, differentiation, and the control of inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christina Berube, Louis-Martin Boucher, Weili Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0506475102"}], "href": "https://doi.org/10.1073/pnas.0506475102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16183742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16183742"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Elena M Ribe, Ying Y Jean, Rebecca L Goldstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal caspase 2 activity and function requires RAIDD, but not PIDD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20111588"}], "href": "https://doi.org/10.1042/BJ20111588"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22515271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22515271"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "L Peintner, L Dorstyn, S Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tumor-modulatory effects of Caspase-2 and Pidd1 do not require the scaffold protein Raidd."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2015.31"}], "href": "https://doi.org/10.1038/cdd.2015.31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25857265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25857265"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "R Felmer, S Horvat, M Clinton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Raidd cDNA inhibits differentiation of mouse preadipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Prolif (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1365-2184.2003.00253.x"}], "href": "https://doi.org/10.1046/j.1365-2184.2003.00253.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12558660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12558660"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qing Lin, Yan Liu, Daniel J Moore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: the \"death\" adaptor CRADD/RAIDD targets BCL10 and suppresses agonist-induced cytokine expression in T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1101502"}], "href": "https://doi.org/10.4049/jimmunol.1101502"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22323537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22323537"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Huan Qiao, Yan Liu, Ruth A Veach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.588723"}], "href": "https://doi.org/10.1074/jbc.M114.588723"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24958727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24958727"}]}]}]}