Role of Proteases in Regulating Cell Death Pathways

  • Thomas Divya
  • Sekar Vasudevan
  • Ganapasam SudhandiranEmail author


Cell death is a critical process involved during development, tissue homeostasis, and aging. Multiple forms of cell death exist such as apoptosis (type I cell death), necrosis, and autophagy (type II cell death). Recently, other selective forms of cell death such as pyroptosis, eryptosis, entosis, mitophagy, and oncosis are also reported. These cell death pathways collaborate with each other, and regulation of such mechanisms is crucial for maintaining cellular homeostasis. Interestingly, proteases are the one that mediate the cell death programs, and immense research is focused on elucidating the mechanisms through which protease regulates cell death program. In this chapter, we focus on various cell death pathways and how protease regulates these pathways.


Apoptosis Autophagy Proteases Necroptosis Cell death 



The authors thank the support of University Grants Commission (UGC)-UPE Phase II for carrying out a part of work in calcium signaling.


  1. 1.
    Green DR, Llambi F (2015) Cell death signaling. Cold Spring Harb Perspect Biol 7(12):a006080PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Galluzzi L, Lopez-Soto A, Kumar S, Kroemer G (2016) Caspases connect cell-death signaling to organismal homeostasis. Immunity 44(2):221–231PubMedCrossRefGoogle Scholar
  3. 3.
    Ashkenazi A, Salvesen G (2014) Regulated cell death: signaling and mechanisms. Annu Rev Cell Dev Biol 30:337–356PubMedCrossRefGoogle Scholar
  4. 4.
    Puente XS, Sanchez LM, Overall CM, Lopez-Otin C (2003) Human and mouse proteases: a comparative genomic approach. Nat Rev Genet 4(7):544–558PubMedCrossRefGoogle Scholar
  5. 5.
    Davie EW, Ratnoff OD (1964) Waterfall sequence for intrinsic blood clotting. Science 145(1310):1312–3638Google Scholar
  6. 6.
    Macfarlane RG (1964) An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 202:498–499PubMedCrossRefGoogle Scholar
  7. 7.
    Bulteau AL, Bayot A (2011) Mitochondrial proteases and cancer. Biochim Biophys Acta 1807(6):595–601PubMedCrossRefGoogle Scholar
  8. 8.
    Troy CM, Jean YY (2015) Caspases: therapeutic targets in neurologic disease. Neurotherapeutics 12(1):42–48PubMedCrossRefGoogle Scholar
  9. 9.
    Qureshi N, Morrison DC, Reis J (2012) Proteasome protease mediated regulation of cytokine induction and inflammation. Biochim Biophys Acta 1823(11):2087–2093PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Azevedo A, Prado AF, Antonio RC, Issa JP, Gerlach RF (2014) Matrix metalloproteinases are involved in cardiovascular diseases. Basic Clin Pharmacol Toxicol 115(4):301–314PubMedCrossRefGoogle Scholar
  11. 11.
    Verdoes M, Verhelst SH (2016) Detection of protease activity in cells and animals. Biochim Biophys Acta 1864(1):130–142PubMedCrossRefGoogle Scholar
  12. 12.
    Lopez-Otin C, Bond JS (2008) Proteases: multifunctional enzymes in life and disease. J Biol Chem 283(45):30433–30437PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Scott CJ, Taggart CC (2010) Biologic protease inhibitors as novel therapeutic agents. Biochimie 92(11):1681–1688PubMedCrossRefGoogle Scholar
  14. 14.
    Joyce JA, Hanahan D (2004) Multiple roles for cysteine cathepsins in cancer. Cell Cycle 3(12):619–1516CrossRefGoogle Scholar
  15. 15.
    Jedeszko C, Sloane BF (2004) Cysteine cathepsins in human cancer. Biol Chem 385(11):1017–1027PubMedCrossRefGoogle Scholar
  16. 16.
    Henneke I, Greschus S, Savai R, Korfei M, Markart P, Mahavadi P, Schermuly RT, Wygrecka M, Stürzebecher J, Seeger W, Günther A, Ruppert C (2010) Inhibition of urokinase activity reduces primary tumor growth and metastasis formation in a murine lung carcinoma model. Am J Respir Crit Care Med 181(6):611–619PubMedCrossRefGoogle Scholar
  17. 17.
    Mitchell BS (2003) The proteasome–an emerging therapeutic target in cancer. N Engl J Med 348(26):2597–2598PubMedCrossRefGoogle Scholar
  18. 18.
    Ciechanover A (1994) The ubiquitin-proteasome proteolytic pathway. Cell 79(1):13–21PubMedCrossRefGoogle Scholar
  19. 19.
    Hochstrasser M (1995) Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol 72(2):2215–2223Google Scholar
  20. 20.
    Barrett AJ (1970) Cathepsin D. Purification of isoenzymes from human and chicken liver. Biochem J 117(3):601–607PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Li NG, Tang YP, Duan JA, Shi ZH (2014) Matrix metalloproteinase inhibitors: a patent review (2011–2013). Expert Opin Ther Pat 24(9):1039–1052PubMedCrossRefGoogle Scholar
  22. 22.
    Turk B (2006) Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discov 5(9):785–799CrossRefPubMedGoogle Scholar
  23. 23.
    Turk B, Turk D, Turk V (2012) Protease signalling: the cutting edge. EMBO J 31(7):1630–1643PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J et al (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356(6372):768–774PubMedCrossRefGoogle Scholar
  25. 25.
    Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82(2):373–428PubMedCrossRefGoogle Scholar
  26. 26.
    Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25(1):9–34PubMedCrossRefGoogle Scholar
  27. 27.
    Gocheva V, Joyce JA (2007) Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle 6(1):60–64CrossRefPubMedGoogle Scholar
  28. 28.
    Duffy MJ (1996) Proteases as prognostic markers in cancer. Clin Cancer Res 2(4):613–618PubMedGoogle Scholar
  29. 29.
    Hu L, Roth JM, Brooks P, Luty J, Karpatkin S (2008) Thrombin up-regulates cathepsin D which enhances angiogenesis, growth, and metastasis. Cancer Res 68(12):4666–4673CrossRefPubMedGoogle Scholar
  30. 30.
    Martinelli P, Rugarli E (2010) Emerging roles of mitochondrial proteases in neurodegeneration. Biochim Biophys Acta 1797(1):1–10PubMedCrossRefGoogle Scholar
  31. 31.
    Tatsuta T, Augustin S, Nolden M, Friedrichs B, Langer T (2007) m-AAA protease-driven membrane dislocation allows intramembrane cleavage by rhomboid in mitochondria. EMBO J 26(2):325–335PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Schuliga M (2015) The inflammatory actions of coagulant and fibrinolytic proteases in disease. Mediators Inflamm 437695Google Scholar
  33. 33.
    Xie Y, Gao K, Häkkinen L, Larjava HS (2009) Mice lacking beta6 integrin in skin show accelerated wound repair in dexamethasone impaired wound healing model. Wound Repair Regen 17(3):326–339PubMedCrossRefGoogle Scholar
  34. 34.
    Florsheim E, Yu S, Bragatto I, Faustino L, Gomes E, Ramos RN, Barbuto JA, Medzhitov R, Russo M (2015) Integrated innate mechanisms involved in airway allergic inflammation to the serine protease subtilisin. J Immunol 194(10):4621–4630PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Vicencio JM, Galluzzi L, Tajeddine N, Ortiz C, Criollo A, Tasdemir E, Morselli E, Ben Younes A, Maiuri MC, Lavandero S, Kroemer G (2007) Senescence, apoptosis or autophagy? When a damaged cell must decide its path–a mini-review. Gerontology 54(2):92–99CrossRefGoogle Scholar
  36. 36.
    Xiong S, Mu T, Wang G, Jiang X (2014) Mitochondria-mediated apoptosis in mammals. Protein Cell 5(10):737–749PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Zhang Y, Herman B (2002) Ageing and apoptosis. Mech Ageing Dev 123(4):245–260PubMedCrossRefGoogle Scholar
  38. 38.
    Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45(3):528–537PubMedCrossRefGoogle Scholar
  39. 39.
    Hochreiter-Hufford A, Ravichandran KS (2013) Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol 5(1):a008748PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Henson PM, Bratton DL (2013) Antiinflammatory effects of apoptotic cells. J Clin Invest 123(7):2773–2774PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    McIlwain DR, Berger T, Mak TW (2013) Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 5(4):a008656PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Ellis HM, Horvitz HR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44(6):817–829PubMedCrossRefGoogle Scholar
  43. 43.
    Czabotar PE, Lessene G, Strasser A, Adams JM (2014) Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 15(1):49–63PubMedCrossRefGoogle Scholar
  44. 44.
    Gaur U, Aggarwal BB (2003) Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol 66(8):1403–1408PubMedCrossRefGoogle Scholar
  45. 45.
    Fulda S (2015) Targeting extrinsic apoptosis in cancer: challenges and opportunities. Semin Cell Dev Biol 39:20–25PubMedCrossRefGoogle Scholar
  46. 46.
    Goll DE, Thompson VF, Li H, Wei W, Cong J (2003) The calpain system. Physiol Rev 83(3):731–801CrossRefPubMedGoogle Scholar
  47. 47.
    Hu H, Li X, Li Y, Wang L, Mehta S, Feng Q, Chen R, Peng T (2009) Calpain-1 induces apoptosis in pulmonary microvascular endothelial cells under septic conditions. Microvasc Res 78(1):33–39PubMedCrossRefGoogle Scholar
  48. 48.
    Covington MD, Schnellmann RG (2012) Chronic high glucose downregulates mitochondrial calpain 10 and contributes to renal cell death and diabetes-induced renal injury. Kidney Int 81(4):391–400PubMedCrossRefGoogle Scholar
  49. 49.
    Bajaj G, Sharma RK (2006) TNF-alpha-mediated cardiomyocyte apoptosis involves caspase-12 and calpain. Biochem Biophys Res Commun 345(4):1558–1564PubMedCrossRefGoogle Scholar
  50. 50.
    de Duve C (2005) The lysosome turns fifty. Nat Cell Biol 7(9):847–849PubMedCrossRefGoogle Scholar
  51. 51.
    Deiss LP, Galinka H, Berissi H, Cohen O, Kimchi A (1996) Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha. EMBO J 15(15):3861–3870PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Turk B, Stoka V (2007) Protease signalling in cell death: caspases versus cysteine cathepsins. FEBS Lett 581(15):2761–2767PubMedCrossRefGoogle Scholar
  53. 53.
    Timmer JC, Salvesen GS (2007) Caspase substrates. Cell Death Differ 14(1):66–72PubMedCrossRefGoogle Scholar
  54. 54.
    Cirman T, Oresic K, Mazovec GD, Turk V, Reed JC, Myers RM, Salvesen GS, Turk B (2004) Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins. J Biol Chem 279(5):3578–3587PubMedCrossRefGoogle Scholar
  55. 55.
    Blomgran R, Zheng L, Stendahl O (2007) Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization. J Leukoc Biol 81(5):1213–1223PubMedCrossRefGoogle Scholar
  56. 56.
    Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94(4):491–501PubMedCrossRefGoogle Scholar
  57. 57.
    Bidere N, Lorenzo HK, Carmona S, Laforge M, Harper F, Dumont C, Senik A (2003) Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J Biol Chem 278(33):31401–31411PubMedCrossRefGoogle Scholar
  58. 58.
    Droga-Mazovec G, Bojic L, Petelin A, Ivanova S, Romih R, Repnik U, Salvesen GS, Stoka V, Turk V, Turk B (2008) Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues. J Biol Chem 283(27):19140–19150PubMedCrossRefGoogle Scholar
  59. 59.
    Klionsky DJ (2007) Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 8(11):931–937PubMedCrossRefGoogle Scholar
  60. 60.
    He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Klionsky DJ, Cuervo AM, Dunn WA Jr, Levine B, van der Klei I, Seglen PO (2007) How shall I eat thee? Autophagy 3(5):413–416PubMedCrossRefGoogle Scholar
  62. 62.
    Klionsky DJ (2005) The molecular machinery of autophagy: unanswered questions. J Cell Sci 118(Pt 1):7–18PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124(3):471–484PubMedCrossRefGoogle Scholar
  64. 64.
    Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13(10):722–737PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132(1):27–42PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Rubinsztein DC, Mariño G, Kroemer G (2011) Autophagy and aging. Cell 146(5):682–695PubMedCrossRefGoogle Scholar
  67. 67.
    Lang T, Schaeffeler E, Bernreuther D, Bredschneider M, Wolf DH, Thumm M (1998) Aut2p and Aut7p, two novel microtubule-associated proteins are essential for delivery of autophagic vesicles to the vacuole. EMBO J 17(13):3597–3607PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Marino G, Uria JA, Puente XS, Quesada V, Bordallo J, Lopez-Otin C (2003) Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J Biol Chem 278(6):3671–3678PubMedCrossRefGoogle Scholar
  69. 69.
    Li M, Hou Y, Wang J, Chen X, Shao ZM, Yin XM (2011) Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J Biol Chem 286(9):7327–73238PubMedCrossRefGoogle Scholar
  70. 70.
    Hemelaar J, Lelyveld VS, Kessler BM, Ploegh HL (2003) A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J Biol Chem 278(51):51841–51850PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Kaminskyy VO, Zhivotovsky B (2014) Free radicals in cross talk between autophagy and apoptosis. Antioxid Redox Signal 21(1):86–102PubMedCrossRefGoogle Scholar
  72. 72.
    Norman JM, Cohen GM, Bampton ET (2015) The in vitro cleavage of the hAtg proteins by cell death proteases. Autophagy 6(8):1042–1056CrossRefGoogle Scholar
  73. 73.
    Wolf J, Dewi DL, Fredebohm J, Müller-Decker K, Flechtenmacher C, Hoheisel JD, Boettcher M (2013) A mammosphere formation RNAi screen reveals that ATG4A promotes a breast cancer stem-like phenotype. Breast Cancer Res 15(6):R109PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Marino G, Salvador-Montoliu N, Fueyo A, Knecht E, Mizushima N, López-Otin C (2007) Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J Biol Chem 282(25):18573–18583PubMedCrossRefGoogle Scholar
  75. 75.
    Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8(9):741–752PubMedCrossRefGoogle Scholar
  76. 76.
    Debnath J, Baehrecke EH, Kroemer G (2005) Does autophagy contribute to cell death? Autophagy 1(2):66–74PubMedCrossRefGoogle Scholar
  77. 77.
    Denton D, Nicolson S, Kumar S (2012) Cell death by autophagy: facts and apparent artefacts. Cell Death Differ 19(1):87–95PubMedCrossRefGoogle Scholar
  78. 78.
    Cho DH, Jo YK, Hwang JJ, Lee YM, Roh SA, Kim JC (2009) Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells. Cancer Lett 274(1):95–100PubMedCrossRefGoogle Scholar
  79. 79.
    Norman JM, Cohen GM, Bampton ET (2010) The in vitro cleavage of the hAtg proteins by cell death proteases. Autophagy 6(8):1042–1056PubMedCrossRefGoogle Scholar
  80. 80.
    Boland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, Nixon RA (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci 28(27):6926–6937PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Kroemer G, Jaattela M (2005) Lysosomes and autophagy in cell death control. Nat Rev Cancer 5(11):886–897PubMedCrossRefGoogle Scholar
  82. 82.
    Vanlangenakker N, Vanden Berghe T, Krysko DV, Festjens N, Vandenabeele P (2008) Molecular mechanisms and pathophysiology of necrotic cell death. Curr Mol Med 8(3):207–220PubMedCrossRefGoogle Scholar
  83. 83.
    Poon IK, Hulett MD, Parish CR (2010) Molecular mechanisms of late apoptotic/necrotic cell clearance. Cell Death Differ 17(3):381–397PubMedCrossRefGoogle Scholar
  84. 84.
    Jacobson LS, Lima H Jr, Goldberg MF, Gocheva V, Tsiperson V, Sutterwala FS, Joyce JA, Gapp BV, Blomen VA, Chandran K, Brummelkamp TR, Diaz-Griffero F, Brojatsch J (2013) Cathepsin-mediated necrosis controls the adaptive immune response by Th2 (T helper type 2)-associated adjuvants. J Biol Chem 288(11):7481–7491PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Ueda N, Walker PD, Hsu SM, Shah SV (1995) Activation of a 15-kDa endonuclease in hypoxia/reoxygenation injury without morphologic features of apoptosis. Proc Natl Acad Sci U S A 92(16):7202–7206PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Ueda N, Shah SV (2000) Tubular cell damage in acute renal failure-apoptosis, necrosis, or both. Nephrol Dial Transplant 15(3):318–323PubMedCrossRefGoogle Scholar
  87. 87.
    Meli E, Pangallo M, Picca R, Baronti R, Moroni F, Pellegrini-Giampietro DE (2004) Differential role of poly(ADP-ribose) polymerase-1in apoptotic and necrotic neuronal death induced by mild or intense NMDA exposure in vitro. Mol Cell Neurosci 25(1):172–180PubMedCrossRefGoogle Scholar
  88. 88.
    Wang X, Ryter SW, Dai C, Tang ZL, Watkins SC, Yin XM, Song R, Choi AM (2003) Necrotic cell death in response to oxidant stress involves the activation of the apoptogenic caspase-8/bid pathway. J Biol Chem 278(31):29184–29191PubMedCrossRefGoogle Scholar
  89. 89.
    Lockshin RA, Zakeri Z (2002) Caspase-independent cell deaths. Curr Opin Cell Biol 14(6):727–733PubMedCrossRefGoogle Scholar
  90. 90.
    Newton K, Manning G (2016) Necroptosis and Inflammation. Annu Rev Biochem 85:743–763PubMedCrossRefGoogle Scholar
  91. 91.
    Wilson NS, Dixit V, Ashkenazi A (2009) Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol 10(4):348–355PubMedCrossRefGoogle Scholar
  92. 92.
    Vanden Berghe T, Vanlangenakker N, Parthoens E, Deckers W, Devos M, Festjens N, Guerin CJ, Brunk UT, Declercq W, Vandenabeele P (2010) Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ 17(6):922–930PubMedCrossRefGoogle Scholar
  93. 93.
    Chen D, Yu J (1865) Zhang L (2016) Necroptosis: an alternative cell death program defending against cancer. Biochim Biophys Acta 2:228–236Google Scholar
  94. 94.
    Degterev A, Hitomi J, Germscheid M, Ch’en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4(5):313–321PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Zychlinsky A, Prevost MC, Sansonetti PJ (1992) Shigella flexneri induces apoptosis in infected macrophages. Nature 358(6382):167–169PubMedCrossRefGoogle Scholar
  96. 96.
    Cookson BT, Brennan MA (2001) Pro-inflammatory programmed cell death. Trends Microbiol 9(3):113–114PubMedCrossRefGoogle Scholar
  97. 97.
    Fink SL, Cookson BT (2006) Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol 8(11):1812–1825PubMedCrossRefGoogle Scholar
  98. 98.
    Yang JR, Yao FH, Zhang JG, Ji ZY, Li KL, Zhan J, Tong YN, Lin LR, He YN (2014) Ischemia-reperfusion induces renal tubule pyroptosis via the CHOP-caspase-11 pathway. Am J Physiol Renal Physiol 306(1):F75–F84PubMedCrossRefGoogle Scholar
  99. 99.
    Pilla DM, Hagar JA, Haldar AK, Mason AK, Degrandi D, Pfeffer K, Ernst RK, Yamamoto M, Miao EA, Coers J (2014) Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS. Proc Natl Acad Sci U S A 111(16):6046–6051PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Yang D, He Y, Munoz-Planillo R, Liu Q, Nunez G (2015) Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock. Immunity 43(5):923–932PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Cerqueira DM, Pereira MS, Silva AL, Cunha LD, Zamboni DS (2015) Caspase-1 but not caspase-11 is required for NLRC4-mediated pyroptosis and restriction of infection by flagellated legionella species in mouse macrophages and in vivo. J Immunol 195(5):2303–2311PubMedCrossRefGoogle Scholar
  102. 102.
    Bosman GJ, Willekens FL, Werre JM (2005) Erythrocyte aging: a more than superficial resemblance to apoptosis? Cell Physiol Biochem 16(1–3):1–8PubMedCrossRefGoogle Scholar
  103. 103.
    Berg CP, Engels IH, Rothbart A, Lauber K, Renz A, Schlosser SF, Schulze-Osthoff K, Wesselborg S (2001) Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis. Cell Death Differ 8(12):1197–1206PubMedCrossRefGoogle Scholar
  104. 104.
    Bratosin D, Estaquier J, Petit F, Arnoult D, Quatannens B, Tissier JP, Slomianny C, Sartiaux C, Alonso C, Huart JJ, Montreuil J, Ameisen JC (2001) Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria. Cell Death Differ 8(12):1143–1156PubMedCrossRefGoogle Scholar
  105. 105.
    Weil M, Jacobson MD, Raff MC (1998) Are caspases involved in the death of cells with a transcriptionally inactive nucleus? Sperm and chicken erythrocytes. J Cell Sci 111(Pt 18):2707–2715PubMedGoogle Scholar
  106. 106.
    Ogen-Shtern N, Ben David T, Lederkremer GZ (2016) Protein aggregation and ER stress. Brain Res pii: S0006-8993(16)30183-4Google Scholar
  107. 107.
    Naidoo N (2009) ER and aging-protein folding and the ER stress response. Ageing Res Rev 8(3):150–159PubMedCrossRefGoogle Scholar
  108. 108.
    Kaufman RJ, Scheuner D, Schröder M, Shen X, Lee K, Liu CY, Arnold SM (2002) The unfolded protein response in nutrient sensing and differentiation. Nat Rev Mol Cell Biol 3(6):411–421PubMedCrossRefGoogle Scholar
  109. 109.
    Xu C, Bailly-Maitre B, Reed JC (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115(10):2656–2664PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403(6765):98–103PubMedCrossRefGoogle Scholar
  111. 111.
    Nakagawa T, Yuan J (2000) Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 150(4):887–894PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Fischer H, Koenig U, Eckhart L, Tschachler E (2002) Human caspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun 293(2):722–726PubMedCrossRefGoogle Scholar
  113. 113.
    Saleh M, Vaillancourt JP, Graham RK, Huyck M, Srinivasula SM, Alnemri ES, Steinberg MH, Nolan V, Baldwin CT, Hotchkiss RS, Buchman TG, Zehnbauer BA, Hayden MR, Farrer LA, Roy S, Nicholson DW (2004) Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature 429(6987):75–79PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Thomas Divya
    • 1
  • Sekar Vasudevan
    • 1
  • Ganapasam Sudhandiran
    • 1
    Email author
  1. 1.Cell Biology Laboratory, Department of BiochemistryUniversity of MadrasChennaiIndia

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