1932

Abstract

Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases are activated via macromolecular signaling complexes that bring inactive procaspases together and promote their proximity-induced autoactivation and proteolytic processing. Activation of caspases ultimately results in programmed execution of cell death, and the nature of this cell death is determined by the specific caspases involved. Pioneering new research has unraveled distinct roles and cross talk of caspases in the regulation of programmed cell death, inflammation, and innate immune responses. In-depth understanding of these mechanisms is essential to foster the development of precise therapeutic targets to treat autoinflammatory disorders, infectious diseases, and cancer. This review focuses on mechanisms governing caspase activation and programmed cell death with special emphasis on the recent progress in caspase cross talk and caspase-driven gasdermin D–induced pyroptosis.

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2020-04-26
2024-06-21
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Literature Cited

  1. 1. 
    Pasparakis M, Vandenabeele P. 2015. Necroptosis and its role in inflammation. Nature 517:311–20
    [Google Scholar]
  2. 2. 
    Bergsbaken T, Fink SL, Cookson BT 2009. Pyroptosis: host cell death and inflammation. Nat. Rev. Microbiol. 7:99–109
    [Google Scholar]
  3. 3. 
    Man SM, Karki R, Kanneganti TD 2017. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol. Rev. 277:61–75
    [Google Scholar]
  4. 4. 
    Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA et al. 1996. Human ICE/CED-3 protease nomenclature. Cell 87:171
    [Google Scholar]
  5. 5. 
    Man SM, Kanneganti TD. 2016. Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat. Rev. Immunol. 16:7–21
    [Google Scholar]
  6. 6. 
    Lamkanfi M, Declercq W, Kalai M, Saelens X, Vandenabeele P 2002. Alice in caspase land: a phylogenetic analysis of caspases from worm to man. Cell Death Differ 9:358–61
    [Google Scholar]
  7. 7. 
    Ramirez MLG, Salvesen GS. 2018. A primer on caspase mechanisms. Semin. Cell Dev. Biol. 82:79–85
    [Google Scholar]
  8. 8. 
    Shi Y. 2004. Caspase activation: revisiting the induced proximity model. Cell 117:855–58
    [Google Scholar]
  9. 9. 
    Galluzzi L, Lopez-Soto A, Kumar S, Kroemer G 2016. Caspases connect cell-death signaling to organismal homeostasis. Immunity 44:221–31
    [Google Scholar]
  10. 10. 
    Kesavardhana S, Kanneganti TD. 2017. Mechanisms governing inflammasome activation, assembly and pyroptosis induction. Int. Immunol. 29:201–10
    [Google Scholar]
  11. 11. 
    Fava LL, Schuler F, Sladky V, Haschka MD, Soratroi C et al. 2017. The PIDDosome activates p53 in response to supernumerary centrosomes. Genes Dev 31:34–45
    [Google Scholar]
  12. 12. 
    Tinel A, Tschopp J. 2004. The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304:843–46
    [Google Scholar]
  13. 13. 
    Wang XJ, Cao Q, Zhang Y, Su XD 2015. Activation and regulation of caspase-6 and its role in neurodegenerative diseases. Annu. Rev. Pharmacol. Toxicol. 55:553–72
    [Google Scholar]
  14. 14. 
    Guo H, Albrecht S, Bourdeau M, Petzke T, Bergeron C, LeBlanc AC 2004. Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease. Am. J. Pathol. 165:523–31
    [Google Scholar]
  15. 15. 
    Ruchaud S, Korfali N, Villa P, Kottke TJ, Dingwall C et al. 2002. Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation. EMBO J 21:1967–77
    [Google Scholar]
  16. 16. 
    Eckhart L, Declercq W, Ban J, Rendl M, Lengauer B et al. 2000. Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation. J. Investig. Dermatol. 115:1148–51
    [Google Scholar]
  17. 17. 
    Lippens S, Kockx M, Knaapen M, Mortier L, Polakowska R et al. 2000. Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing. Cell Death Differ 7:1218–24
    [Google Scholar]
  18. 18. 
    Martinon F, Burns K, Tschopp J 2002. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10:417–26
    [Google Scholar]
  19. 19. 
    Park HH, Lo YC, Lin SC, Wang L, Yang JK, Wu H 2007. The death domain superfamily in intracellular signaling of apoptosis and inflammation. Annu. Rev. Immunol. 25:561–86
    [Google Scholar]
  20. 20. 
    Henry CM, Martin SJ. 2017. Caspase-8 acts in a non-enzymatic role as a scaffold for assembly of a pro-inflammatory “FADDosome” complex upon TRAIL stimulation. Mol. Cell 65:715–29.e5
    [Google Scholar]
  21. 21. 
    Budd RC, Yeh WC, Tschopp J 2006. cFLIP regulation of lymphocyte activation and development. Nat. Rev. Immunol. 6:196–204
    [Google Scholar]
  22. 22. 
    Kang S, Fernandes-Alnemri T, Rogers C, Mayes L, Wang Y et al. 2015. Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3. Nat. Commun. 6:7515
    [Google Scholar]
  23. 23. 
    Gurung P, Anand PK, Malireddi RK, Vande Walle L, Van Opdenbosch N et al. 2014. FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. J. Immunol. 192:1835–46
    [Google Scholar]
  24. 24. 
    Cunha LD, Silva ALN, Ribeiro JM, Mascarenhas DPA, Quirino GFS et al. 2017. AIM2 engages active but unprocessed caspase-1 to induce noncanonical activation of the NLRP3 inflammasome. Cell Rep 20:794–805
    [Google Scholar]
  25. 25. 
    Oberst A, Dillon CP, Weinlich R, McCormick LL, Fitzgerald P et al. 2011. Catalytic activity of the caspase-8-FLIPL complex inhibits RIPK3-dependent necrosis. Nature 471:363–67
    [Google Scholar]
  26. 26. 
    Van Opdenbosch N, Van Gorp H, Verdonckt M, Saavedra PHV, de Vasconcelos NM et al. 2017. Caspase-1 engagement and TLR-induced c-FLIP expression suppress ASC/caspase-8-dependent apoptosis by inflammasome sensors NLRP1b and NLRC4. Cell Rep 21:3427–44
    [Google Scholar]
  27. 27. 
    Boatright KM, Renatus M, Scott FL, Sperandio S, Shin H et al. 2003. A unified model for apical caspase activation. Mol. Cell 11:529–41
    [Google Scholar]
  28. 28. 
    Chang DW, Xing Z, Capacio VL, Peter ME, Yang X 2003. Interdimer processing mechanism of procaspase-8 activation. EMBO J 22:4132–42
    [Google Scholar]
  29. 29. 
    Muzio M, Stockwell BR, Stennicke HR, Salvesen GS, Dixit VM 1998. An induced proximity model for caspase-8 activation. J. Biol. Chem. 273:2926–30
    [Google Scholar]
  30. 30. 
    Kerr JF, Wyllie AH, Currie AR 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239–57
    [Google Scholar]
  31. 31. 
    Taylor RC, Cullen SP, Martin SJ 2008. Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9:231–41
    [Google Scholar]
  32. 32. 
    Arandjelovic S, Ravichandran KS. 2015. Phagocytosis of apoptotic cells in homeostasis. Nat. Immunol. 16:907–17
    [Google Scholar]
  33. 33. 
    McIlwain DR, Berger T, Mak TW 2013. Caspase functions in cell death and disease. Cold Spring Harb. Perspect. Biol. 5:a008656
    [Google Scholar]
  34. 34. 
    Parrish AB, Freel CD, Kornbluth S 2013. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb. Perspect. Biol. 5:a008672
    [Google Scholar]
  35. 35. 
    Tait SW, Green DR. 2010. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat. Rev. Mol. Cell Biol. 11:621–32
    [Google Scholar]
  36. 36. 
    Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW 2002. Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol. Cell 9:423–32
    [Google Scholar]
  37. 37. 
    Cain K, Bratton SB, Cohen GM 2002. The Apaf-1 apoptosome: a large caspase-activating complex. Biochimie 84:203–14
    [Google Scholar]
  38. 38. 
    Shiozaki EN, Chai J, Shi Y 2002. Oligomerization and activation of caspase-9, induced by Apaf-1 CARD. PNAS 99:4197–202
    [Google Scholar]
  39. 39. 
    Shiozaki EN, Shi Y. 2004. Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology. Trends Biochem. Sci. 29:486–94
    [Google Scholar]
  40. 40. 
    Kondylis V, Kumari S, Vlantis K, Pasparakis M 2017. The interplay of IKK, NF-κB and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation. Immunol. Rev. 277:113–27
    [Google Scholar]
  41. 41. 
    Peltzer N, Walczak H. 2019. Cell death and inflammation—a vital but dangerous liaison. Trends Immunol 40:387–402
    [Google Scholar]
  42. 42. 
    Ting AT, Bertrand MJM. 2016. More to life than NF-κB in TNFR1 signaling. Trends Immunol 37:535–45
    [Google Scholar]
  43. 43. 
    Horn S, Hughes MA, Schilling R, Sticht C, Tenev T et al. 2017. Caspase-10 negatively regulates caspase-8-mediated cell death, switching the response to CD95L in favor of NF-κB activation and cell survival. Cell Rep 19:785–97
    [Google Scholar]
  44. 44. 
    Lamy L, Ngo VN, Emre NC, Shaffer AL 3rd, Yang Y et al. 2013. Control of autophagic cell death by caspase-10 in multiple myeloma. Cancer Cell 23:435–49
    [Google Scholar]
  45. 45. 
    Wang J, Zheng L, Lobito A, Chan FK, Dale J et al. 1999. Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 98:147–58
    [Google Scholar]
  46. 46. 
    Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK et al. 2002. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419:6905395–99
    [Google Scholar]
  47. 47. 
    Juo P, Kuo CJ, Yuan J, Blenis J 1998. Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr. Biol. 8:1001–8
    [Google Scholar]
  48. 48. 
    Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS et al. 1998. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9:267–76
    [Google Scholar]
  49. 49. 
    Yeh WC, Itie A, Elia AJ, Ng M, Shu HB et al. 2000. Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Immunity 12:633–42
    [Google Scholar]
  50. 50. 
    Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U et al. 2009. XIAP discriminates between type I and type II FAS-induced apoptosis. Nature 460:1035–39
    [Google Scholar]
  51. 51. 
    Olsson M, Vakifahmetoglu H, Abruzzo PM, Hogstrand K, Grandien A, Zhivotovsky B 2009. DISC-mediated activation of caspase-2 in DNA damage-induced apoptosis. Oncogene 28:1949–59
    [Google Scholar]
  52. 52. 
    Sidi S, Sanda T, Kennedy RD, Hagen AT, Jette CA et al. 2008. Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3. Cell 133:864–77
    [Google Scholar]
  53. 53. 
    Newton K, Manning G. 2016. Necroptosis and inflammation. Annu. Rev. Biochem. 85:743–63
    [Google Scholar]
  54. 54. 
    Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A et al. 2008. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol. Cell 30:689–700
    [Google Scholar]
  55. 55. 
    Mahoney DJ, Cheung HH, Mrad RL, Plenchette S, Simard C et al. 2008. Both cIAP1 and cIAP2 regulate TNFα-mediated NF-κB activation. PNAS 105:11778–83
    [Google Scholar]
  56. 56. 
    Feoktistova M, Geserick P, Kellert B, Dimitrova DP, Langlais C et al. 2011. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol. Cell 43:449–63
    [Google Scholar]
  57. 57. 
    Tenev T, Bianchi K, Darding M, Broemer M, Langlais C et al. 2011. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol. Cell 43:432–48
    [Google Scholar]
  58. 58. 
    Green DR. 2019. The coming decade of cell death research: five riddles. Cell 177:1094–107
    [Google Scholar]
  59. 59. 
    Van Opdenbosch N, Lamkanfi M 2019. Caspases in cell death, inflammation, and disease. Immunity 50:1352–64
    [Google Scholar]
  60. 60. 
    Kalai M, Van Loo G, Vanden Berghe T, Meeus A, Burm W et al. 2002. Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA. Cell Death Differ 9:981–94
    [Google Scholar]
  61. 61. 
    Yeh WC, de la Pompa JL, McCurrach ME, Shu HB, Elia AJ et al. 1998. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 279:1954–58
    [Google Scholar]
  62. 62. 
    Zhang J, Cado D, Chen A, Kabra NH, Winoto A 1998. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Nature 392:296–300
    [Google Scholar]
  63. 63. 
    Bossaller L, Chiang PI, Schmidt-Lauber C, Ganesan S, Kaiser WJ et al. 2012. Cutting edge: FAS (CD95) mediates noncanonical IL-1β and IL-18 maturation via caspase-8 in an RIP3-independent manner. J. Immunol. 189:5508–12
    [Google Scholar]
  64. 64. 
    Kovalenko A, Kim JC, Kang TB, Rajput A, Bogdanov K et al. 2009. Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease. J. Exp. Med. 206:2161–77
    [Google Scholar]
  65. 65. 
    Kang TB, Ben-Moshe T, Varfolomeev EE, Pewzner-Jung Y, Yogev N et al. 2004. Caspase-8 serves both apoptotic and nonapoptotic roles. J. Immunol. 173:2976–84
    [Google Scholar]
  66. 66. 
    Li C, Lasse S, Lee P, Nakasaki M, Chen SW et al. 2010. Development of atopic dermatitis-like skin disease from the chronic loss of epidermal caspase-8. PNAS 107:22249–54
    [Google Scholar]
  67. 67. 
    Kaiser WJ, Upton JW, Long AB, Livingston-Rosanoff D, Daley-Bauer LP et al. 2011. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature 471:368–72
    [Google Scholar]
  68. 68. 
    Zhang H, Zhou X, McQuade T, Li J, Chan FK, Zhang J 2011. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature 471:373–76
    [Google Scholar]
  69. 69. 
    O'Donnell MA, Perez-Jimenez E, Oberst A, Ng A, Massoumi R et al. 2011. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat. Cell Biol. 13:1437–42
    [Google Scholar]
  70. 70. 
    Kesavardhana S, Kuriakose T, Guy CS, Samir P, Malireddi RKS et al. 2017. ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death. J. Exp. Med. 214:2217–29
    [Google Scholar]
  71. 71. 
    Kuriakose T, Man SM, Malireddi RK, Karki R, Kesavardhana S et al. 2016. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci. Immunol. 1:aag2045
    [Google Scholar]
  72. 72. 
    Upton JW, Kaiser WJ, Mocarski ES 2012. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe 11:290–97
    [Google Scholar]
  73. 73. 
    Chu LH, Indramohan M, Ratsimandresy RA, Gangopadhyay A, Morris EP et al. 2018. The oxidized phospholipid oxPAPC protects from septic shock by targeting the non-canonical inflammasome in macrophages. Nat. Commun. 9:996
    [Google Scholar]
  74. 74. 
    Zanoni I, Tan Y, Di Gioia M, Broggi A, Ruan J et al. 2016. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science 352:1232–36
    [Google Scholar]
  75. 75. 
    Shi J, Gao W, Shao F 2017. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem. Sci. 42:245–54
    [Google Scholar]
  76. 76. 
    Boyden ED, Dietrich WF. 2006. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat. Genet. 38:240–44
    [Google Scholar]
  77. 77. 
    Kanneganti TD, Ozoren N, Body-Malapel M, Amer A, Park JH et al. 2006. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440:233–36
    [Google Scholar]
  78. 78. 
    Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K et al. 2006. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–32
    [Google Scholar]
  79. 79. 
    Martinon F, Agostini L, Meylan E, Tschopp J 2004. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr. Biol. 14:1929–34
    [Google Scholar]
  80. 80. 
    Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–41
    [Google Scholar]
  81. 81. 
    Franchi L, Amer A, Body-Malapel M, Kanneganti TD, Ozoren N et al. 2006. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nat. Immunol. 7:576–82
    [Google Scholar]
  82. 82. 
    Miao EA, Alpuche-Aranda CM, Dors M, Clark AE, Bader MW et al. 2006. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf. Nat. Immunol. 7:569–75
    [Google Scholar]
  83. 83. 
    Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG et al. 2010. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. PNAS 107:3076–80
    [Google Scholar]
  84. 84. 
    Zhao Y, Yang J, Shi J, Gong YN, Lu Q et al. 2011. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature 477:596–600
    [Google Scholar]
  85. 85. 
    Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458:509–13
    [Google Scholar]
  86. 86. 
    Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G et al. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514–18
    [Google Scholar]
  87. 87. 
    Burckstummer T, Baumann C, Bluml S, Dixit E, Durnberger G et al. 2009. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10:266–72
    [Google Scholar]
  88. 88. 
    Roberts TL, Idris A, Dunn JA, Kelly GM, Burnton CM et al. 2009. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323:1057–60
    [Google Scholar]
  89. 89. 
    Chae JJ, Wood G, Masters SL, Richard K, Park G et al. 2006. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production. PNAS 103:9982–87
    [Google Scholar]
  90. 90. 
    Xu H, Yang J, Gao W, Li L, Li P et al. 2014. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature 513:237–41
    [Google Scholar]
  91. 91. 
    Evavold CL, Ruan J, Tan Y, Xia S, Wu H, Kagan JC 2018. The pore-forming protein gasdermin D regulates interleukin-1 secretion from living macrophages. Immunity 48:35–44.e6
    [Google Scholar]
  92. 92. 
    Black RA, Kronheim SR, Sleath PR 1989. Activation of interleukin-1β by a co-induced protease. FEBS Lett 247:386–90
    [Google Scholar]
  93. 93. 
    Kostura MJ, Tocci MJ, Limjuco G, Chin J, Cameron P et al. 1989. Identification of a monocyte specific pre-interleukin 1β convertase activity. PNAS 86:5227–31
    [Google Scholar]
  94. 94. 
    Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S et al. 2011. Non-canonical inflammasome activation targets caspase-11. Nature 479:117–21
    [Google Scholar]
  95. 95. 
    Shi J, Zhao Y, Wang Y, Gao W, Ding J et al. 2014. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514:187–92
    [Google Scholar]
  96. 96. 
    Lamkanfi M, Dixit VM. 2014. Mechanisms and functions of inflammasomes. Cell 157:1013–22
    [Google Scholar]
  97. 97. 
    Kalai M, Lamkanfi M, Denecker G, Boogmans M, Lippens S et al. 2003. Regulation of the expression and processing of caspase-12. J. Cell Biol. 162:457–67
    [Google Scholar]
  98. 98. 
    Nakagawa T, Yuan J. 2000. Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis. J. Cell Biol. 150:887–94
    [Google Scholar]
  99. 99. 
    Di Sano F, Ferraro E, Tufi R, Achsel T, Piacentini M, Cecconi F 2006. Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism. J. Biol. Chem. 281:2693–700
    [Google Scholar]
  100. 100. 
    Nakagawa T, Zhu H, Morishima N, Li E, Xu J et al. 2000. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 403:98–103
    [Google Scholar]
  101. 101. 
    Saleh M, Mathison JC, Wolinski MK, Bensinger SJ, Fitzgerald P et al. 2006. Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440:1064–68
    [Google Scholar]
  102. 102. 
    Salvamoser R, Brinkmann K, O'Reilly LA, Whitehead L, Strasser A, Herold MJ 2019. Characterisation of mice lacking the inflammatory caspases-1/11/12 reveals no contribution of caspase-12 to cell death and sepsis. Cell Death Differ 26:1124–37
    [Google Scholar]
  103. 103. 
    Vande Walle L, Jimenez Fernandez D, Demon D, Van Laethem N, Van Hauwermeiren F et al. 2016. Does caspase-12 suppress inflammasome activation. ? Nature 534:E1–4
    [Google Scholar]
  104. 104. 
    Fink SL, Cookson BT. 2006. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol 8:1812–25
    [Google Scholar]
  105. 105. 
    Hilbi H, Moss JE, Hersh D, Chen Y, Arondel J et al. 1998. Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB. J. Biol. Chem. 273:32895–900
    [Google Scholar]
  106. 106. 
    Monack DM, Raupach B, Hromockyj AE, Falkow S 1996. Salmonella typhimurium invasion induces apoptosis in infected macrophages. PNAS 93:9833–38
    [Google Scholar]
  107. 107. 
    Vande Walle L, Lamkanfi M 2016. Pyroptosis. Curr. Biol. 26:R568–72
    [Google Scholar]
  108. 108. 
    Broz P, Ruby T, Belhocine K, Bouley DM, Kayagaki N et al. 2012. Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1. Nature 490:288–91
    [Google Scholar]
  109. 109. 
    Kang SJ, Wang S, Hara H, Peterson EP, Namura S et al. 2000. Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions. J. Cell Biol. 149:613–22
    [Google Scholar]
  110. 110. 
    Wang S, Miura M, Jung Y, Zhu H, Gagliardini V et al. 1996. Identification and characterization of Ich-3, a member of the interleukin-1β converting enzyme (ICE)/Ced-3 family and an upstream regulator of ICE. J. Biol. Chem. 271:20580–87
    [Google Scholar]
  111. 111. 
    Wang J, Sahoo M, Lantier L, Warawa J, Cordero H et al. 2018. Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18. PLOS Pathog 14:e1007105
    [Google Scholar]
  112. 112. 
    Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM et al. 2014. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505:509–14
    [Google Scholar]
  113. 113. 
    Monroe KM, Yang Z, Johnson JR, Geng X, Doitsh G et al. 2014. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science 343:428–32
    [Google Scholar]
  114. 114. 
    Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K et al. 2015. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526:666–71
    [Google Scholar]
  115. 115. 
    Shi J, Zhao Y, Wang K, Shi X, Wang Y et al. 2015. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526:660–65
    [Google Scholar]
  116. 116. 
    Agard NJ, Maltby D, Wells JA 2010. Inflammatory stimuli regulate caspase substrate profiles. Mol. Cell Proteom. 9:880–93
    [Google Scholar]
  117. 117. 
    Kayagaki N, Lee BL, Stowe IB, Kornfeld OS, O'Rourke K et al. 2019. IRF2 transcriptionally induces GSDMD expression for pyroptosis. Sci. Signal. 12:eaax4917
    [Google Scholar]
  118. 118. 
    Feng S, Fox D, Man SM 2018. Mechanisms of gasdermin family members in inflammasome signaling and cell death. J. Mol. Biol. 430:3068–80
    [Google Scholar]
  119. 119. 
    Kovacs SB, Miao EA. 2017. Gasdermins: effectors of pyroptosis. Trends Cell Biol 27:673–84
    [Google Scholar]
  120. 120. 
    Wang Y, Gao W, Shi X, Ding J, Liu W et al. 2017. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547:99–103
    [Google Scholar]
  121. 121. 
    Rogers C, Fernandes-Alnemri T, Mayes L, Alnemri D, Cingolani G, Alnemri ES 2017. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat. Commun. 8:14128
    [Google Scholar]
  122. 122. 
    Aglietti RA, Estevez A, Gupta A, Ramirez MG, Liu PS et al. 2016. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. PNAS 113:7858–63
    [Google Scholar]
  123. 123. 
    Ding J, Wang K, Liu W, She Y, Sun Q et al. 2016. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535:111–16
    [Google Scholar]
  124. 124. 
    Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG et al. 2016. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535:153–58
    [Google Scholar]
  125. 125. 
    Sborgi L, Ruhl S, Mulvihill E, Pipercevic J, Heilig R et al. 2016. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J 35:1766–78
    [Google Scholar]
  126. 126. 
    Mulvihill E, Sborgi L, Mari SA, Pfreundschuh M, Hiller S, Muller DJ 2018. Mechanism of membrane pore formation by human gasdermin-D. EMBO J 37:e98321
    [Google Scholar]
  127. 127. 
    Davis MA, Fairgrieve MR, Den Hartigh A, Yakovenko O, Duvvuri B et al. 2019. Calpain drives pyroptotic vimentin cleavage, intermediate filament loss, and cell rupture that mediates immunostimulation. PNAS 116:5061–70
    [Google Scholar]
  128. 128. 
    de Vasconcelos NM, Van Opdenbosch N, Van Gorp H, Parthoens E, Lamkanfi M 2019. Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture. Cell Death Differ 26:146–61
    [Google Scholar]
  129. 129. 
    Nakanishi K, Maruyama M, Shibata T, Morishima N 2001. Identification of a caspase-9 substrate and detection of its cleavage in programmed cell death during mouse development. J. Biol. Chem. 276:41237–44
    [Google Scholar]
  130. 130. 
    Byun Y, Chen F, Chang R, Trivedi M, Green KJ, Cryns VL 2001. Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis. Cell Death Differ 8:443–50
    [Google Scholar]
  131. 131. 
    Kambara H, Liu F, Zhang X, Liu P, Bajrami B et al. 2018. Gasdermin D exerts anti-inflammatory effects by promoting neutrophil death. Cell Rep 22:2924–36
    [Google Scholar]
  132. 132. 
    Sollberger G, Choidas A, Burn GL, Habenberger P, Di Lucrezia R et al. 2018. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps. Sci. Immunol. 3:eaar6689
    [Google Scholar]
  133. 133. 
    Chen KW, Monteleone M, Boucher D, Sollberger G, Ramnath D et al. 2018. Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps. Sci. Immunol. 3:eaar6676
    [Google Scholar]
  134. 134. 
    Martin-Sanchez F, Diamond C, Zeitler M, Gomez AI, Baroja-Mazo A et al. 2016. Inflammasome-dependent IL-1β release depends upon membrane permeabilisation. Cell Death Differ 23:1219–31
    [Google Scholar]
  135. 135. 
    Karmakar M, Katsnelson M, Malak HA, Greene NG, Howell SJ et al. 2015. Neutrophil IL-1β processing induced by pneumolysin is mediated by the NLRP3/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux. J. Immunol. 194:1763–75
    [Google Scholar]
  136. 136. 
    Chen KW, Gross CJ, Sotomayor FV, Stacey KJ, Tschopp J et al. 2014. The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute Salmonella challenge. Cell Rep 8:570–82
    [Google Scholar]
  137. 137. 
    Ruan J, Xia S, Liu X, Lieberman J, Wu H 2018. Cryo-EM structure of the gasdermin A3 membrane pore. Nature 557:62–67
    [Google Scholar]
  138. 138. 
    Liu Z, Wang C, Yang J, Zhou B, Yang R et al. 2019. Crystal structures of the full-length murine and human gasdermin D reveal mechanisms of autoinhibition, lipid binding, and oligomerization. Immunity 51:43–49.e4
    [Google Scholar]
  139. 139. 
    Liu Z, Wang C, Rathkey JK, Yang J, Dubyak GR et al. 2018. Structures of the gasdermin D C-terminal domains reveal mechanisms of autoinhibition. Structure 26:778–84.e3
    [Google Scholar]
  140. 140. 
    Kuang S, Zheng J, Yang H, Li S, Duan S et al. 2017. Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in cell pyroptosis. PNAS 114:10642–47
    [Google Scholar]
  141. 141. 
    Liu Z, Wang C, Yang J, Zhou B, Yang R et al. 2019. Crystal structures of the full-length murine and human gasdermin D reveal mechanisms of autoinhibition, lipid binding, and oligomerization. Immunity 51:143–49.e4
    [Google Scholar]
  142. 142. 
    Ruhl S, Broz P. 2015. Caspase-11 activates a canonical NLRP3 inflammasome by promoting K+ efflux. Eur. J. Immunol. 45:2927–36
    [Google Scholar]
  143. 143. 
    Banerjee I, Behl B, Mendonca M, Shrivastava G, Russo AJ et al. 2018. Gasdermin D restrains type I interferon response to cytosolic DNA by disrupting ionic homeostasis. Immunity 49:413–26.e5
    [Google Scholar]
  144. 144. 
    Zhu Q, Zheng M, Balakrishnan A, Karki R, Kanneganti TD 2018. Gasdermin D promotes AIM2 inflammasome activation and is required for host protection against Francisella novicida. J. Immunol 201:3662–68
    [Google Scholar]
  145. 145. 
    Ruhl S, Shkarina K, Demarco B, Heilig R, Santos JC, Broz P 2018. ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation. Science 362:956–60
    [Google Scholar]
  146. 146. 
    Gong YN, Guy C, Olauson H, Becker JU, Yang M et al. 2017. ESCRT-III acts downstream of MLKL to regulate necroptotic cell death and its consequences. Cell 169:286–300.e16
    [Google Scholar]
  147. 147. 
    Kanneganti A, Malireddi RKS, Saavedra PHV, Vande Walle L, Van Gorp H et al. 2018. GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever. J. Exp. Med. 215:1519–29
    [Google Scholar]
  148. 148. 
    Xiao J, Wang C, Yao JC, Alippe Y, Xu C et al. 2018. Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice. PLOS Biol 16:e3000047
    [Google Scholar]
  149. 149. 
    Dubois H, Sorgeloos F, Sarvestani ST, Martens L, Saeys Y et al. 2019. Nlrp3 inflammasome activation and Gasdermin D-driven pyroptosis are immunopathogenic upon gastrointestinal norovirus infection. PLOS Pathog 15:e1007709
    [Google Scholar]
  150. 150. 
    Wu C, Lu W, Zhang Y, Zhang G, Shi X et al. 2019. Inflammasome activation triggers blood clotting and host death through pyroptosis. Immunity 50:1401–11.e4
    [Google Scholar]
  151. 151. 
    Karki R, Lee E, Place D, Samir P, Mavuluri J et al. 2018. IRF8 regulates transcription of Naips for NLRC4 inflammasome activation. Cell 173:920–33.e13
    [Google Scholar]
  152. 152. 
    Karki R, Kanneganti TD. 2019. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat. Rev. Cancer 19:197–214
    [Google Scholar]
  153. 153. 
    Wang WJ, Chen D, Jiang MZ, Xu B, Li XW et al. 2018. Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins. J. Dig. Dis. 19:74–83
    [Google Scholar]
  154. 154. 
    Malireddi RKS, Gurung P, Mavuluri J, Dasari TK, Klco JM et al. 2018. TAK1 restricts spontaneous NLRP3 activation and cell death to control myeloid proliferation. J. Exp. Med. 215:1023–34
    [Google Scholar]
  155. 155. 
    Samir P, Kesavardhana S, Patmore DM, Gingras S, Malireddi RKS et al. 2019. DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome. Nature 573:590–94
    [Google Scholar]
  156. 156. 
    Lukens JR, Gurung P, Vogel P, Johnson GR, Carter RA et al. 2014. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 516:246–49
    [Google Scholar]
  157. 157. 
    Cassel SL, Janczy JR, Bing X, Wilson SP, Olivier AK et al. 2014. Inflammasome-independent IL-1β mediates autoinflammatory disease in Pstpip2-deficient mice. PNAS 111:1072–77
    [Google Scholar]
  158. 158. 
    Lukens JR, Gross JM, Calabrese C, Iwakura Y, Lamkanfi M et al. 2014. Critical role for inflammasome-independent IL-1β production in osteomyelitis. PNAS 111:1066–71
    [Google Scholar]
  159. 159. 
    Maelfait J, Vercammen E, Janssens S, Schotte P, Haegman M et al. 2008. Stimulation of Toll-like receptor 3 and 4 induces interleukin-1β maturation by caspase-8. J. Exp. Med. 205:1967–73
    [Google Scholar]
  160. 160. 
    Gurung P, Lamkanfi M, Kanneganti TD 2015. Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation. J. Immunol. 194:2064–67
    [Google Scholar]
  161. 161. 
    Rickard JA, Anderton H, Etemadi N, Nachbur U, Darding M et al. 2014. TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice. eLife 3:e03464
    [Google Scholar]
  162. 162. 
    Chauhan D, Bartok E, Gaidt MM, Bock FJ, Herrmann J et al. 2018. BAX/BAK-induced apoptosis results in caspase-8-dependent IL-1β maturation in macrophages. Cell Rep 25:2354–68.e5
    [Google Scholar]
  163. 163. 
    Vince JE, De Nardo D, Gao W, Vince AJ, Hall C et al. 2018. The mitochondrial apoptotic effectors BAX/BAK activate caspase-3 and -7 to trigger NLRP3 inflammasome and caspase-8 driven IL-1β activation. Cell Rep 25:2339–53.e4
    [Google Scholar]
  164. 164. 
    Schneider KS, Gross CJ, Dreier RF, Saller BS, Mishra R et al. 2017. The inflammasome drives GSDMD-independent secondary pyroptosis and IL-1 release in the absence of caspase-1 protease activity. Cell Rep 21:3846–59
    [Google Scholar]
  165. 165. 
    Kang TB, Yang SH, Toth B, Kovalenko A, Wallach D 2013. Caspase-8 blocks kinase RIPK3-mediated activation of the NLRP3 inflammasome. Immunity 38:27–40
    [Google Scholar]
  166. 166. 
    Chen KW, Demarco B, Heilig R, Shkarina K, Boettcher A et al. 2019. Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly. EMBO J 38:e101638
    [Google Scholar]
  167. 167. 
    Rogers C, Erkes DA, Nardone A, Aplin AE, Fernandes-Alnemri T, Alnemri ES 2019. Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation. Nat. Commun. 10:1689
    [Google Scholar]
  168. 168. 
    Mukherjee S, Keitany G, Li Y, Wang Y, Ball HL et al. 2006. Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation. Science 312:1211–4
    [Google Scholar]
  169. 169. 
    Paquette N, Conlon J, Sweet C, Rus F, Wilson L et al. 2012. Serine/threonine acetylation of TGFbeta-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling. PNAS 109:12710–5
    [Google Scholar]
  170. 170. 
    Philip NH, Dillon CP, Snyder AG, Fitzgerald P, Wynosky-Dolfi MA et al. 2014. Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-kappaB and MAPK signaling. PNAS 111:7385–90
    [Google Scholar]
  171. 171. 
    Weng D, Marty-Roix R, Ganesan S, Proulx MK, Vladimer GI et al. 2014. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. PNAS 111:7391–6
    [Google Scholar]
  172. 172. 
    Orning P, Weng D, Starheim K, Ratner D, Best Z et al. 2018. Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science 362:1064–9
    [Google Scholar]
  173. 173. 
    Sarhan J, Liu BC, Muendlein HI, Li P, Nilson R et al. 2018. Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection. PNAS 115:E10888–E97
    [Google Scholar]
  174. 174. 
    Mandal P, Feng Y, Lyons JD, Berger SB, Otani S et al. 2018. Caspase-8 collaborates with caspase-11 to drive tissue damage and execution of endotoxic shock. Immunity 49:42–55.e6
    [Google Scholar]
  175. 175. 
    Sharma D, Malik A, Guy C, Vogel P, Kanneganti TD 2019. TNF/TNFR axis promotes pyrin inflammasome activation and distinctly modulates pyrin inflammasomopathy. J. Clin. Invest. 129:150–62
    [Google Scholar]
  176. 176. 
    McGeough MD, Wree A, Inzaugarat ME, Haimovich A, Johnson CD et al. 2017. TNF regulates transcription of NLRP3 inflammasome components and inflammatory molecules in cryopyrinopathies. J. Clin. Invest. 127:4488–97
    [Google Scholar]
  177. 177. 
    Yang YL, Li XM. 2000. The IAP family: endogenous caspase inhibitors with multiple biological activities. Cell Res 10:169–77
    [Google Scholar]
  178. 178. 
    Zhang J, Webster JD, Dugger DL, Goncharov T, Roose-Girma M et al. 2019. Ubiquitin ligases cIAP1 and cIAP2 limit cell death to prevent inflammation. Cell Rep 27:2679–89.e3
    [Google Scholar]
  179. 179. 
    Fulda S, Vucic D. 2012. Targeting IAP proteins for therapeutic intervention in cancer. Nat. Rev. Drug Discov. 11:109–24
    [Google Scholar]
  180. 180. 
    Labbe K, McIntire CR, Doiron K, Leblanc PM, Saleh M 2011. Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome. Immunity 35:897–907
    [Google Scholar]
  181. 181. 
    Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C et al. 2014. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513:90–4
    [Google Scholar]
  182. 182. 
    Takahashi N, Vereecke L, Bertrand MJ, Duprez L, Berger SB et al. 2014. RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 513:95–9
    [Google Scholar]
  183. 183. 
    Fu Y, Comella N, Tognazzi K, Brown LF, Dvorak HF, Kocher O 1999. Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display. Gene 240:157–63
    [Google Scholar]
  184. 184. 
    Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K et al. 2009. DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep 10:916–22
    [Google Scholar]
  185. 185. 
    Thapa RJ, Ingram JP, Ragan KB, Nogusa S, Boyd DF et al. 2016. DAI senses influenza A virus genomic RNA and activates RIPK3-dependent cell death. Cell Host Microbe 20:674–81
    [Google Scholar]
  186. 186. 
    Lin J, Kumari S, Kim C, Van TM, Wachsmuth L et al. 2016. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature 540:124–8
    [Google Scholar]
  187. 187. 
    Newton K, Wickliffe KE, Maltzman A, Dugger DL, Strasser A et al. 2016. RIPK1 inhibits ZBP1-driven necroptosis during development. Nature 540:129–33
    [Google Scholar]
  188. 188. 
    Law RH, Zhang Q, McGowan S, Buckle AM, Silverman GA et al. 2006. An overview of the serpin superfamily. Genome Biol 7:216
    [Google Scholar]
  189. 189. 
    Ray CA, Black RA, Kronheim SR, Greenstreet TA, Sleath PR et al. 1992. Viral inhibition of inflammation: Cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69:597–604
    [Google Scholar]
  190. 190. 
    Zhou Q, Snipas S, Orth K, Muzio M, Dixit VM, Salvesen GS 1997. Target protease specificity of the viral serpin CrmA. Analysis of five caspases. J. Biol. Chem. 272:7797–800
    [Google Scholar]
  191. 191. 
    Young JL, Sukhova GK, Foster D, Kisiel W, Libby P, Schonbeck U 2000. The serpin proteinase inhibitor 9 is an endogenous inhibitor of interleukin 1beta-converting enzyme (caspase-1) activity in human vascular smooth muscle cells. J. Exp. Med. 191:1535–44
    [Google Scholar]
  192. 192. 
    Choi YJ, Kim S, Choi Y, Nielsen TB, Yan J et al. 2019. SERPINB1-mediated checkpoint of inflammatory caspase activation. Nat. Immunol. 20:276–87
    [Google Scholar]
  193. 193. 
    Li J, Yin HL, Yuan J 2008. Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity. J. Cell Biol. 181:321–33
    [Google Scholar]
  194. 194. 
    Jin J, Yu Q, Han C, Hu X, Xu S et al. 2013. LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition. Nat. Commun. 4:2075
    [Google Scholar]
  195. 195. 
    Chen R, Zeng L, Zhu S, Liu J, Zeh HJ et al. 2019. cAMP metabolism controls caspase-11 inflammasome activation and pyroptosis in sepsis. Sci. Adv. 5:eaav5562
    [Google Scholar]
  196. 196. 
    Fuentes-Prior P, Salvesen GS. 2004. The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem. J. 384:201–32
    [Google Scholar]
  197. 197. 
    MacKenzie SH, Schipper JL, Clark AC 2010. The potential for caspases in drug discovery. Curr. Opin. Drug Discov. Devel. 13:568–76
    [Google Scholar]
  198. 198. 
    Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E 2018. Targeting the NLRP3 inflammasome in inflammatory diseases. Nat. Rev. Drug Discov. 17:588–606
    [Google Scholar]
  199. 199. 
    Perera AP, Fernando R, Shinde T, Gundamaraju R, Southam B et al. 2018. MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice. Sci. Rep. 8:8618
    [Google Scholar]
  200. 200. 
    Lamkanfi M, Dixit VM. 2017. A new lead to NLRP3 inhibition. J. Exp. Med. 214:3147–9
    [Google Scholar]
  201. 201. 
    Ahn H, Kang SG, Yoon SI, Ko HJ, Kim PH et al. 2017. Methylene blue inhibits NLRP3, NLRC4, AIM2, and non-canonical inflammasome activation. Sci. Rep. 7:12409
    [Google Scholar]
  202. 202. 
    Lamkanfi M, Mueller JL, Vitari AC, Misaghi S, Fedorova A et al. 2009. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol. 187:61–70
    [Google Scholar]
  203. 203. 
    Van Gorp H, Lamkanfi M 2019. The emerging roles of inflammasome-dependent cytokines in cancer development. EMBO Rep 20:e47575
    [Google Scholar]
  204. 204. 
    Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E et al. 2009. Use of canakinumab in the cryopyrin-associated periodic syndrome. N. Engl. J. Med. 360:2416–25
    [Google Scholar]
  205. 205. 
    Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P et al. 2017. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390:1833–42
    [Google Scholar]
  206. 206. 
    Yang J, Liu Z, Wang C, Yang R, Rathkey JK et al. 2018. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. PNAS 115:6792–97
    [Google Scholar]
  207. 207. 
    Rathkey JK, Zhao J, Liu Z, Chen Y, Yang J et al. 2018. Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci. Immunol. 3:eaat2738
    [Google Scholar]
  208. 208. 
    Hu JJ, Liu X, Zhao J, Xia S, Ruan J et al. 2019. Identification of pyroptosis inhibitors that target a reactive cysteine in gasdermin D. bioRxiv 365908. https://doi.org/10.1101/365908
    [Crossref]
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