Abstract
Biochemical and genetic analysis of apoptosis has determined that intracellular proteases are key effectors of cell death pathways. In particular, early studies have pointed to the primacy of caspase proteases as mediators of execution. More recently, however, evidence has accumulated that noncaspases, including cathepsins, calpains, granzymes, and the proteasome complex, also have roles in mediating and promoting cell death. An important goal is to understand the importance of distinct noncaspases in various forms of apoptosis, and to determine whether pathways mediated by noncaspase proteases intersect with those mediated by caspases. In this review the roles of noncaspase proteases in the biochemistry of apoptosis will be discussed. Leukemia (2000) 14, 1695–1703.
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References
Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR . The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme Cell 1993 75: 641–652
Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA, Huebner K, Black RA . Molecular cloning of the interleukin-1β converting enzyme Science 1992 256: 97–100
Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Mokineaux SM, Weidner JR, Aunins J, Elliston KO, Ayala JM, Casano FJ, Chin J, Ding GJ-F, Egger LA, Gaffney EP, Limjuco G, Palyha OC, Raju SM, Rolando AM, Salley JP, Yamin T-T, Lee TD, Shively JE, MacCross M, Mumford RA, Schmidt JA, Tocci MJ . A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes Nature 1992 356: 768–774
Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J . Human ICE/CED-3 protease nomenclature Cell 1996 87: 171
Thornberry NA, Lazebnik Y . Caspases: enemies within Science 1998 281: 1312–1316
Orlowski RZ . The role of the ubiquitin-proteasome pathway in apoptosis Cell Death Differ 1999 6: 303–313
Schwartz MK . Tissue cathepsins as tumor markers Clin Chem Acta 1995 237: 67–78
Chapman HA, Riese RJ, Shi GP . Emerging roles for cysteine proteases in human biology Ann Rev Physiol 1997 59: 63–88
Westley B, Rochefort H . A secreted glycoprotein induced by estrogen in human breast cancer cell lines Cell 1980 20: 353–362
Capony F, Rougeot C, Montcourrier P, Cavailles V, Salazar G, Rochefort H . Increased secretion, altered processing and glycosylation of procathepsin D in mammary cancer cells Cancer Res 1989 49: 3904–3909
Erickson AH . Biosynthesis of lysosomal endopeptidases J Cell Biochem 1989 40: 31–41
Fujita H, Tanaka Y, Noguchi Y, Kono A, Himeno M, Kato K . Isolation and sequencing of a cDNA clone encoding rat liver lysosomal cathepsin D and the structure of three forms of mature enzymes Biochem Biophys Res Commun 1991 179: 190–196
Godbold GD, Ahn K, Yeyeodu S, Lee LF, Ting JP, Erickson AH . Biosynthesis and intracellular targeting of the lysosomal aspartic proteinase cathepsin D Adv Exp Med Biol 1998 436: 153–162
Kornblau SM . The role of apoptosis in the pathogenesis, prognosis, and therapy of hematologic malignancies Leukemia 1998 12: (Suppl1) 41–46
Mort JS, Recklies AD . Interrelationship of active and latent secreted human cathepsin B precursors Biochem J 1986 233: 57–63
Sloane BF, Honn KV . Cysteine proteinases and metastasis Cancer Metast Rev 1984 3: 249–263
Briozzo P, Morisset M, Capony F, Rougeot C, Rochefort H . In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells Cancer Res 1988 48: 3688–3692
Leto G, Gebbia N, Rausa L, Tumminello FM . Cathepsin D in the malignant progression of neoplastic disease Anticancer Res 1992 12: 235–240
Mignatti P, Rifkin DB . Biology and biochemistry of proteinases in tumor invasion Physiol Rev 1993 73: 161–195
Thorpe SM, Rochefort H, Garcia M, Freiss G, Christensen IJ, Khalaf S, Paolucci F, Pau B, Rasmussen BB, Rose C . Association between high concentration of 52-kDa cathepsin D and poor prognosis in primary human breast cancer Cancer Res 1989 49: 6008–6014
Tandon AK, Clark GM, Chamness GC, Chirgwin JM, McGuire WL . Cathepsin D and prognosis in breast cancer New Engl J Med 1990 322: 297–302
Kute TE, Shao ZM, Sugg NK, Long RT, Russell GB, Case D . Cathepsin D as a prognostic indicator of node-negative breastcancer patients using both immunoassays and enzymatic assays Cancer Res 1992 52: 198–203
Garcia M, Platet N, Liaudet E, Laurent V, Derocq D, Brouillet J-P, Rochefort H . Biological and clinical significance of cathepsin D in breast cancer metastasis Stem Cells 1996 14: 642–650
English HF, Kyprianou N, Isaacs JT . Relationship between DNA fragmentation and apoptosis in programmed cell death in the rat prostate following castration Prostate 1989 15: 233–250
Walker NI, Bennett RE, Kerr JF . Cell death by apoptosis during involution of the lactating breast in mice and rats Am J Anat 1989 185: 19–32
Guenette RS, Mooibroek M, Wong K, Wong P, Tenniswood M . Cathepsin B, a cysteine protease implicated in metastatic progression, is also expressed during regression of the rat prostate and mammary glands Eur J Biochem 1994 226: 311–321
Sensibar JA, Liu XX, Patai B, Alger B, Lee C . Characterization of castration-induced cell death in the rat prostate by immunohistochemical localization of cathepsin D Prostate 1990 16: 263–276
Roberts LR, Kurosawa H, Bronk SF, Fesmier PJ, Agellon LB, Leung W-Y, Mao F, Gores GJ . Cathepsin B contributes to bile salt-induced apoptosis of rat hepatocytes Gastroenterology 1997 113: 1714–1726
Roberts LR, Adjei PN, Gores GJ . Cathepsins as effector proteases in hepatocyte apoptosis Cell Biochem Biophys 1999 30: 71–88
Nishimura Y, Kawabata T, Kato K . Identification of latent cathepsins B and L in microsomal lumen: characterization of enzymatic activation and proteolytic processing in vitro Arch Biochem Biophys 1988 261: 64–71
Rowan AD, Mason P, Mach L, Mort JS . Rat procathepsin B: Proteolytic processing to the mature form in vitro J Biol Chem 1992 267: 15993–15999
Shibata M, Kanamori S, Isahara K, Ohsawa Y, Konishi A, Kametaka S, Watanabe T, Ebisu S, Ishido K, Kominami E, Uchiyama Y . Participation of cathepsins B and D in apoptosis of PC12 cells following serum deprivation Biochem Biophys Res Commun 1998 251: 199–203
Cataldo AM, Barnett JL, Berman SA, Li J, Quarless S, Bursztajn S, Lippa C, Nixon RA . Gene expression and cellular content of cathepsin D in Alzheimer’s disease brain: evidence for early up-regulation of the endosomal-lysosomal system Neuron 1995 14: 671–680
Isahara K, Ohsawa Y, Kanamori S, Shibata M, Waguri S, Sato N, Gotow T, Watanabe T, Momoi T, Urase K, Kominami E, Uchiyama Y . Regulation of a novel pathway for cell death by lysosomal aspartic and cysteine proteinases Neuroscience 1999 91: 233–249
Lotem J, Sachs L . Control of apoptosis in hematopoiesis and leukemia by cytokines, tumor suppressor and oncogenes Leukemia 1996 10: 925–931
Drexler HG, Zaborski M, Quentmeier H . Cytokine response profiles of human myeloid factor-dependent leukemia cell lines Leukemia 1997 11: 701–708
Antoku K, Liu Z, Johnson DE . IL-3 withdrawal activates a CrmA-insensitive poly(ADP-ribose) polymerase cleavage enzyme in factor-dependent myeloid progenitor cells Leukemia 1998 12: 682–689
Blalock WL, Weinstein-Oppenheimer C, Chang F, Hoyle PE, Wang XY, Algate PA, Franklin RA, Oberhaus SM, Steelman LS, McCubrey JA . Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs Leukemia 1999 13: 1109–1166
Deiss LP, Galinka H, Berissi H, Cohen O, Kimchi A . Cathepsin D protease mediates programmed cell death induced by interferon-γ, Fas/APO-1 and TNF-α EMBO J 1996 15: 3861–3870
Wu GS, Saftig P, Peters C, El-Deiry WS . Potential role for cathepsin D in p53-dependent tumor suppression and chemosensitivity Oncogene 1998 16: 2177–2183
Luo X, Budihardjo I, Zou H, Slaughter C, Wang X . Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors Cell 1998 94: 481–490
Li H, Zhu H, Xu C-J, Yuan J . Cleavage of BID by caspase 8 mediates the mitochondrial damage in Fas pathway of apoptosis Cell 1998 94: 491–501
Friesen C, Fulda S, Debatin KM . Cytotoxic drugs and the CD95 pathway Leukemia 1999 13: 1854–1858
Adams JM, Cory S . The Bcl-2 protein family: arbiters of cell survival Science 1998 281: 1322–1326
Liu X, Zou H, Slaughter C, Wang X . DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis Cell 1997 89: 175–184
Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S . A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD Nature 1998 391: 43–50
Rowan S, Fisher DE . Mechanisms of apoptotic cell death Leukemia 1997 11: 457–465
Wolf BB, Green DR . Suicidal tendencies: apoptotic cell death by caspase family proteinases J Biol Chem 1999 274: 20049–20052
Brunk UT, Zhang H, Roberg K, Ollinger K . Lethal hydrogen peroxide toxicity involves lysosomal iron-catalyzed reactions with membrane damage Redox Rep 1995 1: 267–277
Li W, Yuan XM, Olsson AG, Brunk UT . Uptake of oxidized LDL by macrophages results in partial lysosomal enzyme inactivation and relocation Arterioscler Thromb Vasc Biol 1998 18: 177–184
Roberg K, Ollinger K . Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with ensuing apoptosis in neonatal rat cardiomyocytes Am J Pathol 1998 152: 1151–1156
Vancompernolle K, Van Herreweghe F, Pynaert G, Van de Craen M, De Vos K, Totty N, Sterling A, Fiers W, Vandenabeele P, Grooten J . Atractyloside-induced release of cathepsin B, a protease with caspase-processing activity FEBS Lett 1998 438: 150–158
Zhou Q, Salvesen GS . Activation of pro-caspase-7 by serine proteases includes a non-canonical specificity Biochem J 1997 324: 361–364
Schotte P, Declercq W, Van Huffel S, Vandenabeele P, Beyaert R . Non-specific effects of methyl ketone peptide inhibitors of caspases FEBS Lett 1999 442: 117–121
Guroff G . A neutral, calcium-activated proteinase from the soluble fraction of rat brain J Biol Chem 1964 239: 149–155
Mellgren RL . Canine cardiac calcium-dependent proteases: resolution of two forms with different requirements for calcium FEBS Lett 1980 109: 129–133
Murachi T, Tanaka K, Hatanaka M, Murakami T . Intracellular Ca2+-dependent protease (calpain) and its high-molecular-weight endogenous inhibitor (calpastatin) Adv Enzyme Reg 1981 19: 407–424
Sorimachi H, Saido TC, Suzuki K . New era of calpain research: discovery of tissue-specific calpains FEBS Lett 1994 341: 1–5
Carfoli E, Molinari M . Calpain: a protease in search of a function? Biochem Biophys Res Commun 1998 247: 193–203
Sorimachi H, Ishiura S, Suzuki K . A novel tissue-specific calpain species expressed predominantly in the stomach comprises two alternative splicing products with and without Ca(2+)-binding domain J Biol Chem 1993 268: 19476–19482
Sorimachi H, Toyama-Sorimachi N, Saido TC, Kawasaki H, Sugita H, Miyasaka M, Arahata K, Ishiura S, Suzuki K . Muscle-specific calpain, p94, is degraded by autolysis immediately after translation, resulting in disappearance from muscle J Biol Chem 1993 268: 10593–10605
Wilson R, Ainscough R, Anderson K, Baynes C, Berks M, Bonfield J, Burton J, Connell M, Copsey T, Cooper J, Coulson A, Craxton M, Dear S, Du Z, Durbin R, Favello A, Fraser A, Fulton L, Gardner A, Green P, Hawkins T, Hillier L, Jler M, Johnston L, Jones M, Kershaw J, Kirsten J, Laisster N, Latreille P, Lightning J, Lloyd C, Mortimore B, O’Callaghan M, Parsons J, Percy C, Rifken L, Roopra A, Saunders D, Shownkeen R, Sims M, Smaldon N, Smith A, Smith M, Sonnhammer E, Staden R, Sulston J, Thierry-Mieg J, Thomas K, Vaudin M, Vaughan K, Waterston R, Watson A, Weinstock L, Wilkinson-Sproat J, Wohldman P . 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans Nature 1994 368: 32–38
Sasaki T, Yoshimura N, Kikuchi T, Hatanaka M, Kitahara A, Sakihama T, Murachi T . Similarity and dissimilarity in subunit structures of calpains I and II from various sources as demonstrated by immunological cross-reactivity J Biochem 1983 94: 2055–2061
Murachi T . Intracellular regulatory system involving calpain and calpastatin Biochem Int 1989 18: 263–294
Croall DE, DeMartino GN . Calcium-activated neutral protease (calpain) system: Structure, function, and regulation Physiol Rev 1991 71: 813–847
Blanchard H, Grochulski P, Li Y, Arthur JS, Davies PL, Elce JS, Cygler M . Structure of a calpain Ca(2+)-binding domain reveals a novel EF-hand and Ca(2+)-induced conformational changes Nature Struct Biol 1997 4: 532–538
Molinari M, Anagli J, Carafoli E . Ca(2+)-activated neutral protease is active in the erythrocyte membrane in its nonautolyzed 80-kDa form J Biol Chem 1994 269: 27992–27995
Suzuki K, Tsuji S, Ishiura S, Kimura Y, Kubota S, Imahori K . Autolysis of calcium-activated neutral protease of chicken skeletal muscle J Biochem 1981 90: 1787–1793
Mellgren RL, Repetti A, Muck TC, Easly J . Rabbit skeletal muscle calcium-dependent protease requiring millimolar CA2+. Purification, subunit structure, and Ca2+-dependent autoproteolysis J Biol Chem 1982 257: 7203–7209
DeMartino GN, Huff CA, Croall DE . Autoproteolysis of the small subunit of calcium-dependent protease II activates and regulates protease activity J Biol Chem 1986 261: 12047–12052
Imajoh S, Kawasaki H, Suzuki K . Limited autolysis of calcium-activated neutral protease (CANP): reduction of the Ca2+-requirement is due to the NH2-terminal processing of the large subunit J Biochem 1986 100: 633–642
Inomata M, Kasai Y, Nakamura M, Kawashima S . Activation mechanism of calcium-activated neutral protease. Evidence for the existence of intramolecular and intermolecular autolyses J Biol Chem 1988 263: 19783–19787
Elce JS, Hegadorn C, Arthur JSC . Autolysis, Ca2+ requirement, and heterodimer stability in m-calpain J Biol Chem 1997 272: 11268–11275
Waxman L, Krebs EG . Identification of two protease inhibitors from bovine cardiac muscle J Biol Chem 1978 253: 5888–5891
Emori Y, Kawasaki H, Imajoh S, Imahori K, Suzuki K . Endogenous inhibitor for calcium-dependent cysteine protease contains four internal repeats that could be responsible for its multiple reactive sites Proc Natl Acad Sci USA 1987 84: 3590–3594
Squier MKT, Miller ACK, Malkinson AM, Cohen JJ . Calpain activation in apoptosis J Cell Physiol 1994 159: 229–237
Knepper-Nicolai B, Savill J, Brown SB . Constitutive apoptosis in human neutrophils requires synergy between calpains and the proteosome downstream of caspases J Biol Chem 1998 273: 30530–30536
Waterhouse NJ, Finucane DM, Green DR, Elce JS, Kumar S, Alnemri ES, Litwack G, Khanna KK, Lavin MF, Watters DJ . Calpain activation is upstream of caspases in radiation-induced apoptosis Cell Death Differ 1998 5: 1051–1061
Wood DE, Newcomb EW . Caspase-dependent activation of calpain during drug-induced apoptosis J Biol Chem 1999 274: 8309–8315
Xie H, Johnson GV . Ceramide selectively decreases tau levels in differentiated PC12 cells through modulation of calpain I J Neurochem 1997 69: 1020–1030
Debiasi RL, Squier MKT, Pike B, Wynes M, Dermody TS, Cohen JJ, Tyler KL . Reovirus-induced apoptosis is preceded by increased cellular calpain activity and is blocked by calpain inhibitors J Virol 1999 73: 695–701
Kohli V, Madden JF, Bentley RC, Clavien P-A . Calpain mediates ishemic injury of the liver through modulation of apoptosis and necrosis Gastroenterol 1999 116: 168–178
Saito K, Elce JS, Hamos JE, Nixon RA . Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration Proc Natl Acad Sci USA 1993 90: 2628–2632
Nixon RA, Saito K-I, Grynspan F, Griffin WR, Katayama S, Honda T, Mohan PS, Shea TB, Beermann M . Calcium-activated neutral proteinase (calpain) system in aging and Alzheimer’s disease Ann NY Acad Sci 1994 747: 77–91
Mouatt-Prigent A, Karlsson JO, Agid Y, Hirsch EC . Increased M-calpain expression in the mesencephalon of patients with Parkinson's disease but not in other neurodegenerative disorders involving the mesencephalon: a role in nerve cell death? Neurosci 1996 73: 979–987
Aoyagi T, Takeuchi T, Matsuzaki A, Kawamura K, Kondo S . Leupeptins, new protease inhibitors from Actinomycetes J Antibiotics 1969 22: 283–286
Barrett AJ, Kembhavi AA, Hanada K . E-64 [L-trans-epoxysuccinyl-leucyl-amido(4-guanidino)butane] and related epoxides as inhibitors of cysteine proteinases Acta Biol Med Germ 1981 40: 1513–1517
Wang KK . Developing selective inhibitors of calpain Trends Pharm Sci 1990 11: 139–142
Mehdi S . Cell-penetrating inhibitors of calpain Trends Biochem Sci 1991 16: 150–153
Tsujinaka T, Kajiwara Y, Kambayashi J, Sakon M, Higuchi N, Tanaka T, Mori T . Synthesis of a new cell penetrating inhibitor (calpeptin) Biochem Biophys Res Commun 1988 153: 1201–1208
Wang KK, Nath R, Posner A, Raser KJ, Buroker-Kilgore M, Hajimohammadreza I, Probert W, Marcoux FW, Ye Q, Takano E, Hatanaka M, Maki M, Caner H, Collins JL, Fergus A, Lee KS, Lunney EA, Hays SJ, Yuen P . An alpha-mercaptoacrylic acid derivative is a selective non-peptide cell-permeable calpain inhibitor and is neuroprotective Proc Natl Acad Sci USA 1996 93: 6687–6692
Squier MKT, Cohen JJ . Calpain, an upstream regulator of thymocyte apoptosis J Immunol 1997 158: 3690–3697
Squier MKT, Sehnert AJ, Sellins KS, Malkinson AM, Takano E, Cohen JJ . Calpain and calpastatin regulate neutrophil apoptosis J Cell Physiol 1999 178: 311–319
Vanags DM, Porn-Ares I, Coppola S, Burgess DH, Orrenius S . Protease involvement in fodrin cleavage and phosphatidylserine exposure in apoptosis J Biol Chem 1996 271: 31075–31085
Spinedi A, Oliverio S, Di Sano F, Piacentini M . Calpain involvement in calphostin C-induced apoptosis Biochem Pharm 1998 56: 1489–1492
Wolf BB, Goldstein JC, Stennicke HR, Beere H, Amarante-Mendes GP, Salvesen GS, Green DR . Calpain functions in a caspase-independent manner to promote apoptosis-like events during platelet activation Blood 1999 94: 1683–1692
Gressner AM, Lahme B, Roth S . Attenuation of TGF-beta-induced apoptosis in primary cultures of hepatocytes by calpain inhibitors Biochem Biophys Res Commun 1997 231: 457–462
Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, Pettmann B . Calpain inhibitors, but not caspase inhibitors, prevent actin proteolysis and DNA fragmentation during apoptosis J Cell Sci 1998 111: 713–722
Jordan J, Galindo MF, Miller RJ . Role of calpain- and interleukin-1β converting enzyme-like proteases in the β-amyloid-induced death of rat hippocampal neurons in culture J Neurochem 1997 68: 1612–1621
Yuan Y, Dopheide SM, Ivanidis C, Salem HH, Jackson SP . Calpain regulation of cytoskeletal signaling complexes in von Willebrand factor-stimulated platelets. Distinct roles for glycoprotein Ib-V-IX and glycoprotein IIb-IIIa (integrin alphaIIbbeta3) in von Willebrand factor-induced signal transduction J Biol Chem 1997 272: 21847–21854
Martin SJ, O’Brien GA, Nishioka WK, McGahon AJ, Mahboubi A, Saido TC, Green DR . Proteolysis of fodrin (non-erythroid spectrin) during apoptosis J Biol Chem 1995 270: 6425–6428
Cooray P, Yuan Y, Schoenwaelder SM, Mitchell CA, Salem HH, Jackson SP . Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain Biochem J 1996 318: 41–47
Meredith J Jr, Mu Z, Saido T, Du X . Cleavage of the cytoplasmic domain of integrin β3 subunit during endothelial cell apoptosis J Biol Chem 1998 273: 19525–19531
Kishimoto A, Mikawa K, Hashimotos K, Yasuda I, Tanaka S, Tominaga MT, Kuroda T, Nishizuka Y . Limited proteolysis of protein kinase C subspecies by calcium-dependent neutral protease (calpain) J Biol Chem 1989 264: 4088–4092
McGinnis KM, Whitton MM, Gnegy ME, Wang KKW . Calcium/calmodulin-dependent protein kinase IV is cleaved by caspase-3 and calpain in SH-SY5Y human neuroblastoma cells undergoing apoptosis J Biol Chem 1998 273: 19993–20000
Watanabe N, Vande Woude GF, Ikawa Y, Sagata N . Specific proteolysis of the c-mos proto-oncogene product by calpain on fertilization of Xenopus eggs Nature 1989 342: 505–511
Hirai S, Kawasaki H, Yaniv M, Suzuki K . Degradation of transcription factors, c-Jun and c-Fos, by calpain FEBS Lett 1991 287: 57–61
Watt F, Molloy PL . Specific cleavage of transcription factors by the thiol protease, m-calpain Nucleic Acids Res 1993 21: 5092–5100
Choi YH, Lee SJ, Nguyen P, Jang JS, Lee J, Wu ML, Takano E, Maki M, Henkart PA, Trepel JB . Regulation of cyclin D1 by calpain protease J Biol Chem 1997 272: 28479–28484
Kubbutat MHG, Vousden KH . Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability Mol Cell Biol 1997 17: 460–468
Wood DE, Thomas A, Devi LA, Berman Y, Beavis RC, Reed JC, Newcomb EW . Bax cleavage is mediated by calpain during drug-induced apoptosis Oncogene 1998 17: 1069–1078
Porn-Ares MI, Samali A, Orrenius S . Cleavage of the calpain inhibitor, calpastatin, during apoptosis Cell Death Differ 1998 5: 1028–1033
Wang KKW, Posmantur R, Nadimpalli R, Nath R, Mohan P, Nixon RA, Talanian RV, Keegan M, Herzog L, Allen H . Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis Arch Biochem Biophys 1998 356: 187–196
Berke G . The CTL’s kiss of death Cell 1995 81: 9–12
Kagi D, Lederman B, Burki K, Zinkernagel RM, Hengartner H . Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo Ann Rev Immunol 1996 14: 207–232
Nagata S, Golstein P . The Fas death factor Science 1995 267: 1449–1456
Ashkenazi A, Dixit VM . Death receptors: signaling and modulation Science 1998 281: 1305–1308
Doherty PC . Cell-mediated cytotoxicity Cell 1993 75: 607–612
Shresta S, MacIvor DM, Heusel JW, Russell JH, Ley TJ . Natural killer and lymphokine-activated killer cells require granzyme B for the rapid induction of apoptosis in susceptible target cells Proc Natl Acad Sci USA 1995 92: 5679–5683
Shresta S, Heusel JW, Macivor DM, Wesselschmidt RL, Russell JH, Ley TJ . Granzyme B plays a critical role in cytotoxic lymphocyte-induced apoptosis Immunol Rev 1995 146: 211–221
Masson D, Tschopp J . Isolation of a lytic pore-forming protein (perforin) from cytolytic T lymphocytes J Biol Chem 1985 260: 9069–9072
Young JD-E, Hengartner H, Podack ER, Cohn ZA . Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity Cell 1986 44: 849–859
Tschopp J, Schafer S, Masson D, Peitsch MC, Heusser C . Phosphorylcholine acts as a calcium dependent receptor molecule for lymphocyte perforin Nature 1989 337: 272–274
Smyth MJ, O’Connor MD, Trapani JA . Granzymes: A variety of serine protease specificities encoded by genetically distinct subfamilies J Leuk Biol 1996 60: 555–562
Zunino SJ, Bleackley RC, Martinez J, Hudig D . RNKP-1, a novel natural killer cell-associated serine protease gene cloned from RNK-16 cytotoxic lymphocytes J Immunol 1990 144: 2001–2009
Lobe CG, Havele C, Bleackley RC . Cloning of two genes that are specifically expressed in activated cytotoxic T lymphocytes Proc Natl Acad Sci USA 1986 83: 1448–1452
Odake S, Kam CM, Narasimhan L, Poe M, Blake JT, Krahenbuhl O, Tschopp J, Powers JC . Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins Biochem 1991 30: 2217–2227
Poe M, Blake JT, Boulton DA, Gammon M, Sigal NH, Wu JK, Zweerink HJ . Human cytotoxic lymphocyte granzyme B: its purification from granules and the characterization of substrate and inhibitor specificity J Biol Chem 1991 266: 98–103
Shi L, Kraut RP, Aebersold R, Greenberg AH . A natural killer cell granule protein that induces DNA fragmentation and apoptosis J Exp Med 1992 175: 553–566
Heusel JW, Wesselschmidt RL, Shresta S, Russell JH, Ley TJ . Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells Cell 1994 76: 977–987
Froelich CJ, Orth K, Turbov J, Seth P, Gottlieb R, Babior B, Shah GM, Bleackley RC, Dixit VM, Hanna W . New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind and internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis J Biol Chem 1996 271: 29073–29079
Jans DA, Jans P, Briggs LJ, Sutton V, Trapani JA . Nuclear transport of granzyme B (fragmentin-2) J Biol Chem 1996 271: 30781–30789
Shi L, Mai S, Israels S, Browne K, Trapani JA, Greenberg AH . Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localization J Exp Med 1997 185: 853–866
Pinkoski MJ, Hobman M, Heibein JA, Tomaselli K, Li F, Seth P, Froelich CJ, Bleackley RC . Entry and trafficking of granzyme B in target cells during granzyme B-perforin-mediated apoptosis Blood 1998 92: 1044–1054
Pinkoski MJ, Heibein JA, Barry M, Bleackley RC . Nuclear translocation of granzyme B in target cell apoptosis Cell Death Differ 2000 7: 17–24
Pinkoski MJ, Winkler U, Hudig D, Bleackley RC . Binding of granzyme B in the nucleus of target cells. Recognition of an 80-kilodalton protein J Biol Chem 1996 271: 10225–10229
Trapani JA, Browne KA, Smyth MJ, Jans DA . Localization of granzyme B in the nucleus. A putative role in the mechanism of cytotoxic lymphocyte-mediated apoptosis J Biol Chem 1996 271: 4127–4133
Darmon AJ, Nicholson DW, Bleackley RC . Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B Nature 1995 377: 446–448
Darmon AJ, Ley TJ, Nicholson DW, Bleackley RC . Cleavage of CPP32 by granzyme B represents a critical role for granzyme B in the induction of target cell DNA fragmentation J Biol Chem 1996 271: 21709–21712
Martin SJ, Amarante-Mendes GP, Shi LF, Chuang TH, Casiano CA, O’Brien GA, Fitzgerald P, Tan EM, Bokoch GM, Greenberg AH, Green DR . The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism EMBO J 1996 15: 2407–2416
Quan LT, Tewari M, O’Rourke K, Dixit VM, Snipas SJ, Poirier GG, Ray C, Pickup DJ, Salvesen GS . Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B Proc Natl Acad Sci USA 1996 93: 1972–1976
Fernandes-Alnemri T, Litwack G, Alnemri ES . Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family Cancer Res 1995 55: 2737–2742
Orth K, Chinnaiyan AM, Garg M, Froelich CJ, Dixit VM . The CED-3/ICE-like protease Mch2 is activated during apoptosis and cleaves the death substrate lamin A J Biol Chem 1996 271: 16443–16446
Fernandes-Alnemri T, Takahashi A, Armstrong R, Krebs J, Fritz L, Tomaselli KJ, Wang L, Yu Z, Croce CM, Salvesen G, Earnshaw WC, Litwack G, Alnemri ES . Mch3, a novel human apoptotic cysteine protease highly related to CPP32 Cancer Res 1995 55: 6045–6052
Chinnnaiyan AM, Orth K, Hanna WL, Duan HJ, Poirier GG, Froelich CJ, Dixit VM . Cytotoxic T cell-derived granzyme B activates the apoptotic protease ICE-LAP3 Curr Biol 1996 6: 897–899
Gu Y, Sarnecki C, Fleming MA, Lippke JA, Bleackley RC, Su MS-S . Processing and activation of CMH-1 by granzyme B J Biol Chem 1996 271: 10816–10820
Boldin MP, Goncharov TM, Goltsev YV, Wallach D . Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death Cell 1996 85: 803–815
Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM . FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex Cell 1996 85: 817–827
Duan H, Orth K, Chinnaiyan AM, Poirier GG, Froelich CJ, He W-W, Dixit VM . ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B J Biol Chem 1996 271: 16720–16724
Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES . In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains Proc Natl Acad Sci USA 1996 93: 7464–7469
Medema JP, Toes REM, Scaffidi C, Zheng TS, Flavell RA, Melief CJM, Peter ME, Offringa R, Krammer PH . Cleavage of FLICE (caspase-8) by granzyme B during cytotoxic T lymphocyte-induced apoptosis Eur J Immunol 1997 27: 3492–3498
Van de Craen M, Van den brande I, Declercq W, Irmler M, Beyaert R, Tschopp J, Fiers W, Vandenabeele P . Cleavage of caspase family members by granzyme B: a comparative study in vitro Eur J Immunol 1997 27: 1296–1299
Talanian RV, Yang XH, Turbov J, Seth P, Ghayur T, Casiano CA, Orth K, Froelich CJ . Granule-mediated killing: pathways for granzyme B-initiated apoptosis J Exp Med 1997 186: 1323–1331
Shi L, Chen G, MacDonald G, Bergeron L, Li H, Miura M, Rotello RJ, Miller DK, Li P, Seshadri T, Yuan J, Greenberg AH . Activation of an interleukin 1 converting enzyme-dependent apoptosis pathway by granzyme B Proc Natl Acad Sci USA 1996 93: 11002–11007
Andrade F, Roy S, Nicholson D, Thornberry N, Rosen A, Casciola-Rosen L . Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis Immunity 1998 8: 451–460
Gershenfeld HK, Weissman IL . Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte Science 1986 232: 854–858
Masson D, Zamai M, Tschopp J . Identification of granzyme A isolated from cytotoxic T-lymphocyte-granules as one of the proteases encoded by CTL-specific genes FEBS Lett 1986 208: 84–88
Ebnet K, Hausmann M, Lehmann-Grube F, Mullbacher A, Kopf M, Lamers M, Simon MM . Granzyme A-deficient mice retain potent cell-mediated cytotoxicity EMBO J 1995 14: 4230–4239
Mullbacher A, Ebnet K, Blanden RV, Hla RT, Stehle T, Museteanu C, Simon MM . Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia Proc Natl Acad Sci USA 1996 93: 5783–5787
Shresta S, Graubert TA, Thomas DA, Raptis SZ, Ley TJ . Granzyme A initiates an alternative pathway for granule-mediated apoptosis Immunity 1999 10: 595–605
Hayes MP, Berrebi GA, Henkart PA . Induction of target cell DNA release by the cytotoxic T lymphocyte granule protease granzyme A J Exp Med 1989 170: 933–946
Beresford PJ, Xia Z, Greenberg AH, Lieberman J . Granzyme A loading induces rapid cytolysis and a novel form of DNA damage independently of caspase activation Immunity 1999 10: 585–594
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Johnson, D. Noncaspase proteases in apoptosis. Leukemia 14, 1695–1703 (2000). https://doi.org/10.1038/sj.leu.2401879
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DOI: https://doi.org/10.1038/sj.leu.2401879
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