{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPYCARD, also known as ASC or TMS1, is a bipartite adaptor protein defined by an N‐terminal pyrin domain (PYD) and a C‐terminal caspase recruitment domain (CARD) that plays a pivotal role in innate immunity. By engaging in homotypic PYD–PYD interactions, it bridges upstream pattern recognition receptors (such as NLRP3, AIM2, and cryopyrin) to downstream effectors via CARD–CARD interactions. This leads to its oligomerization into filamentous “specks” that nucleate the activation of pro–caspase‑1, thereby promoting the proteolytic maturation of proinflammatory cytokines (e.g. IL‑1β and IL‑18) and triggering pyroptotic cell death. Structural and biochemical studies have revealed that ASC adopts a flexible conformation that enables dynamic interdomain associations essential for its assembly and regulated signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical function in inflammasome assembly, ASC participates in alternative signaling pathways that regulate cell death and inflammatory gene expression. It can facilitate caspase‑8–dependent apoptosis—as evidenced by its interactions with mitochondrial proapoptotic proteins like Bax in a p53‐dependent manner—and modulate NF‑κB activation. Furthermore, aberrant or heightened engagement of ASC, particularly in the context of mutant sensor proteins (for example, in PAPA syndrome), underscores its role in the amplification of sterile inflammation and in autoinflammatory disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the functional versatility of ASC extends to a broad spectrum of pathological contexts. In infectious diseases, ASC‐mediated inflammasome activation is critical for microbial sensing and cytokine secretion in response to pathogens such as Mycobacterium tuberculosis, Toxoplasma gondii, and Porphyromonas gingivalis. In parallel, its epigenetic silencing through promoter hypermethylation has been implicated in tumorigenesis, with loss of ASC expression compromising proapoptotic and tumor‐suppressive functions in cancers like breast, melanoma, and gastric carcinoma. Recent advances employing high‐resolution imaging and structural analyses have further elucidated ASC’s supramolecular assembly—its filament architecture and interaction interfaces with partners such as cryopyrin and related PAAD/PYRIN proteins—underscoring its central role in inflammatory signal transduction and disease modulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "45"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "K E Conway, B B McConnell, C E Bowring, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Methylation mediated silencing of TMS1/ASC gene in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-5-28"}], "href": "https://doi.org/10.1186/1476-4598-5-28"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16848908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16848908"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Sameer Mirza, Gayatri Sharma, Chandra P Prasad, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.08.029"}], "href": "https://doi.org/10.1016/j.molcel.2007.08.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17964261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17964261"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Ruairi J Fahy, Matthew C Exline, Mikhail A Gavrilin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammasome mRNA expression in human monocytes during early septic shock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Crit Care Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1164/rccm.200703-418OC"}], "href": "https://doi.org/10.1164/rccm.200703-418OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18263805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18263805"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Deepti Verma, Maria Lerm, Robert Blomgran Julinder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: relation to common inflammatory diseases?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.23286"}], "href": "https://doi.org/10.1002/art.23286"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18311798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18311798"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Priya Kapoor-Vazirani, Jacob D Kagey, Doris R Powell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of hMOF-dependent histone H4 lysine 16 acetylation in the maintenance of TMS1/ASC gene activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-0141"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-0141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18701507"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18701507"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Max Tze-Han Huang, Debra J Taxman, Elizabeth A Holley-Guthrie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of apoptotic speck protein containing a caspase recruitment domain (ASC) and NLRP3 in causing necrosis and ASC speck formation induced by Porphyromonas gingivalis in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0800909"}], "href": "https://doi.org/10.4049/jimmunol.0800909"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19201894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19201894"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Nicole B Bryan, Andrea Dorfleutner, Yon Rojanasakul, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0802367"}], "href": "https://doi.org/10.4049/jimmunol.0802367"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19234215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19234215"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Vasudev J Bailey, Hariharan Easwaran, Yi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MS-qFRET: a quantum dot-based method for analysis of DNA methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gr.088831.108"}], "href": "https://doi.org/10.1101/gr.088831.108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19443857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19443857"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Eva de Alba "}, {"type": "b", "children": [{"type": "t", "text": "Structure and interdomain dynamics of apoptosis-associated speck-like protein containing a CARD (ASC)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.024273"}], "href": "https://doi.org/10.1074/jbc.M109.024273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19759015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19759015"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Bibhuti B Mishra, Pedro Moura-Alves, Avinash Sonawane, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1462-5822.2010.01450.x"}], "href": "https://doi.org/10.1111/j.1462-5822.2010.01450.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20148899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20148899"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Erin McElvania Tekippe, Irving C Allen, Paul D Hulseberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0012320"}], "href": "https://doi.org/10.1371/journal.pone.0012320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20808838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20808838"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Debra J Taxman, Elizabeth A Holley-Guthrie, Max Tze-Han Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activated protein kinase (MAPK), and chemokine induction independent of the inflammasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.221077"}], "href": "https://doi.org/10.1074/jbc.M111.221077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21487011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21487011"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Jesus Segovia, Ahmed Sabbah, Victoria Mgbemena, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0029695"}], "href": "https://doi.org/10.1371/journal.pone.0029695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22295065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22295065"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Parimala R Vajjhala, Ruth E Mirams, Justine M Hill "}, {"type": "b", "children": [{"type": "t", "text": "Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.381228"}], "href": "https://doi.org/10.1074/jbc.M112.381228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23066025"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23066025"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Stefan K Drexler, Luca Bonsignore, Mark Masin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue-specific opposing functions of the inflammasome adaptor ASC in the regulation of epithelial skin carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1209171109"}], "href": "https://doi.org/10.1073/pnas.1209171109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23090995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23090995"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Martina Proell, Motti Gerlic, Peter D Mace, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CARD plays a critical role in ASC foci formation and inflammasome signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20121198"}], "href": "https://doi.org/10.1042/BJ20121198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23110696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23110696"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Lanny Gov, Alborz Karimzadeh, Norikiyo Ueno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human innate immunity to Toxoplasma gondii is mediated by host caspase-1 and ASC and parasite GRA15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "mBio (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/mBio.00255-13"}], "href": "https://doi.org/10.1128/mBio.00255-13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23839215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23839215"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Alvin Lu, Venkat Giri Magupalli, Jianbin Ruan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.02.008"}], "href": "https://doi.org/10.1016/j.cell.2014.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24630722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24630722"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Zheng Yin, Tuo Deng, Leif E Peterson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptome analysis of human adipocytes implicates the NOD-like receptor pathway in obesity-induced adipose inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2014.06.018"}], "href": "https://doi.org/10.1016/j.mce.2014.06.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25011057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25011057"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Roberta Scianaro, Antonella Insalaco, Luisa Bracci Laudiero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deregulation of the IL-1β axis in chronic recurrent multifocal osteomyelitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Rheumatol Online J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1546-0096-12-30"}], "href": "https://doi.org/10.1186/1546-0096-12-30"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25061439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25061439"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Fiona Q Bui, Larry Johnson, JoAnn Roberts, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fusobacterium nucleatum infection of gingival epithelial cells leads to NLRP3 inflammasome-dependent secretion of IL-1β and the danger signals ASC and HMGB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cmi.12560"}], "href": "https://doi.org/10.1111/cmi.12560"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26687842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26687842"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Mari H Tervaniemi, Shintaro Katayama, Tiina Skoog, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep22745"}], "href": "https://doi.org/10.1038/srep22745"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26976200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26976200"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Florian I Schmidt, Alvin Lu, Jeff W Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20151790"}], "href": "https://doi.org/10.1084/jem.20151790"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27069117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27069117"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Ulrike Höckendorf, Monica Yabal, Tobias Herold, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2016.06.002"}], "href": "https://doi.org/10.1016/j.ccell.2016.06.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27411587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27411587"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Javier Oroz, Susana Barrera-Vilarmau, Carlos Alfonso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ASC Pyrin Domain Self-associates and Binds NLRP3 Protein Using Equivalent Binding Interfaces."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.741082"}], "href": "https://doi.org/10.1074/jbc.M116.741082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27432880"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27432880"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Jianxiao Shen, Ling Wang, Na Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep34682"}], "href": "https://doi.org/10.1038/srep34682"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27721494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27721494"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Virginie Deswaerte, Paul Nguyen, Alison West, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammasome Adaptor ASC Suppresses Apoptosis of Gastric Cancer Cells by an IL18-Mediated Inflammation-Independent Mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-17-1887"}], "href": "https://doi.org/10.1158/0008-5472.CAN-17-1887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29282220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29282220"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Carmen Venegas, Sathish Kumar, Bernardo S Franklin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature25158"}], "href": "https://doi.org/10.1038/nature25158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29293211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29293211"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Yang Li, Tian-Min Fu, Alvin Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1810524115"}], "href": "https://doi.org/10.1073/pnas.1810524115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30279182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30279182"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Emanuela Brunetto, Lucia De Monte, Gianpaolo Balzano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunother Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40425-019-0521-4"}], "href": "https://doi.org/10.1186/s40425-019-0521-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30760333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30760333"}]}]}]}