Mitochondria-mediated apoptosis in mammals

doi:10.1007/s13238-014-0089-1

Protein Cell

2014, Vol. 5

Issue (10) : 737-749 https://doi.org/10.1007/s13238-014-0089-1

REVIEW

Mitochondria-mediated apoptosis in mammals

Shunbin Xiong¹,Tianyang Mu²,Guowen Wang³,Xuejun Jiang^4,^*(

)

1. Department of Genetics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA
2. Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, 9 Lvshun Road South, Dalian 116044, China
3. Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China
4. Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA

Download: PDF(627 KB)
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

The mitochondria-mediated caspase activation pathway is a major apoptotic pathway characterized by mitochondrial outer membrane permeabilization (MOMP) and subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP is regulated by the Bcl-2 family of proteins. This pathway plays important roles not only in normal development, maintenance of tissue homeostasis and the regulation of immune system, but also in human diseases such as immune disorders, neurodegeneration and cancer. In the past decades the molecular basis of this pathway and the regulatory mechanism have been comprehensively studied, yet a great deal of new evidence indicates that cytochrome c release from mitochondria does not always lead to irreversible cell death, and that caspase activation can also have non-death functions. Thus, many unsolved questions and new challenges are still remaining. Furthermore, the dysfunction of this pathway involved in cancer development is obvious, and targeting the pathway as a therapeutic strategy has been extensively explored, but the efficacy of the targeted therapies is still under development. In this review we will discuss the mitochondria-mediated apoptosis pathway and its physiological roles and therapeutic implications.

Keywords apoptosome Bcl-2 family IAPs IAP antagonists cancer therapy

Corresponding Author(s): Xuejun Jiang

Issue Date: 24 October 2014

Cite this article:

Shunbin Xiong,Tianyang Mu,Guowen Wang, et al. Mitochondria-mediated apoptosis in mammals[J]. Protein Cell, 2014, 5(10): 737-749.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-014-0089-1
https://academic.hep.com.cn/pac/EN/Y2014/V5/I10/737

1	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 Cell9: 423-432 https://doi.org/10.1016/S1097-2765(02)00442-2
2	Ackler S, Xiao Y, Mitten MJ, Foster K, Oleksijew A, Refici M, Schlessinger S, Wang B, Chemburkar SR, Bauch J (2008) ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol Cancer Ther7: 3265-3274 https://doi.org/10.1158/1535-7163.MCT-08-0268
3	Ashkenazi A, Holland P, Eckhardt SG (2008) Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/Tumor necrosis factor-related apoptosisinducing ligand (rhApo2L/TRAIL). J Clin Oncol26: 3621-3630 https://doi.org/10.1200/JCO.2007.15.7198
4	Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL, Korsmeyer SJ (1985) Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell41: 899-906 https://doi.org/10.1016/S0092-8674(85)80070-2
5	Barrett RM, Colnaghi R, Wheatley SP (2011) Threonine 48 in the BIR domain of survivin is critical to its mitotic and anti-apoptotic activities and can be phosphorylated by CK2 in vitro. Cell Cycle10: 538-548 https://doi.org/10.4161/cc.10.3.14758
6	Ben-Ari Z, Pappo O, Cheporko Y, Yasovich N, Offen D, Shainberg A, Leshem D, Sulkes J, Vidne BA, Hochhauser E (2007) Bax ablation protects against hepatic ischemia/reperfusion injury in transgenic mice. Liver Transplant13: 1181-1188 https://doi.org/10.1002/lt.21221
7	Beug ST, Cheung HH, Lacasse EC, Korneluk RG (2012) Modulation of immune signalling by inhibitors of apoptosis. Trends Immunol33(11): 535-545 https://doi.org/10.1016/j.it.2012.06.004
8	Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P, Bergman J, Wiman KG, Selivanova G (2002) Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med8: 282-288 https://doi.org/10.1038/nm0302-282
9	Cao X, Yap JL, Newell-Rogers MK, Peddaboina C, Jiang W, Papaconstantinou HT, Jupitor D, Rai A, Jung KY, Tubin RP (2013) The novel BH3 alpha-helix mimetic JY-1-106 induces apoptosis in a subset of cancer cells (lung cancer, colon cancer and mesothelioma) by disrupting Bcl-xL and Mcl-1 protein-protein interactions with Bak. Mol Cancer12: 42 https://doi.org/10.1186/1476-4598-12-42
10	Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P (1998) Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell94: 727-737 https://doi.org/10.1016/S0092-8674(00)81732-8
11	Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y (2000) Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature406: 855-862 https://doi.org/10.1038/35022514
12	Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y, Dataa P (2001) Structural basis of caspase-7 inhibition by XIAP. Cell104: 769-780 https://doi.org/10.1016/S0092-8674(01)00272-0
13	Chan FK (2012) Fueling the flames: mammalian programmed necrosis in inflammatory diseases. Cold Spring Harb Perspect Biol4(11). doi: https://doi.org/10.1101/cshperspect.a008805
14	Chen DJ, Huerta S (2009) Smac mimetics as new cancer therapeutics. Anticancer Drugs20: 646-658 https://doi.org/10.1097/CAD.0b013e32832ced78
15	Chen P, Nordstrom W, Gish B, Abrams JM (1996) Grim, a novel cell death gene in Drosophila. Genes Dev10: 1773-1782 https://doi.org/10.1101/gad.10.14.1773
16	Chen R, Valencia I, Zhong F, McColl KS, Roderick HL, Bootman MD, Berridge MJ, Conway SJ, Holmes AB, Mignery GA (2004) Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J cell biol166: 193-203 https://doi.org/10.1083/jcb.200309146
17	Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ (2001) BCL-2, BCL-X(L) sequester BH3 domainonly molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell8: 705-711 https://doi.org/10.1016/S1097-2765(01)00320-3
18	Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell137: 1112-1123 https://doi.org/10.1016/j.cell.2009.05.037
19	Crook NE, Clem RJ, Miller LK (1993) An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol67: 2168-2174
20	Danial NN, Gramm CF, Scorrano L, Zhang CY, Krauss S, Ranger AM, Datta SR, Greenberg ME, Licklider LJ, Lowell BB (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature424: 952-956 https://doi.org/10.1038/nature01825
21	Danial NN, Gimenez-Cassina A, Tondera D (2010) Homeostatic functions of BCL-2 proteins beyond apoptosis. Adv Exp Med Biol687: 1-32 https://doi.org/10.1007/978-1-4419-6706-0_1
22	Devarajan E, Sahin AA, Chen JS, Krishnamurthy RR, Aggarwal N, Brun AM, Sapino A, Zhang F, Sharma D, Yang XH (2002) Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene21: 8843-8851 https://doi.org/10.1038/sj.onc.1206044
23	Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature388: 300-304 https://doi.org/10.1038/40901
24	Deveraux QL, Reed JC (1999) IAP family proteins-suppressors of apoptosis. Genes Dev13: 239-252 https://doi.org/10.1101/gad.13.3.239
25	Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell102: 33-42 https://doi.org/10.1016/S0092-8674(00)00008-8
26	Dubrez L, Berthelet J, Glorian V (2013) IAP proteins as targets for drug development in oncology. Onco Targets Ther9: 1285-1304 https://doi.org/10.2147/OTT.S33375
27	Edison N, Zuri D, Maniv I, Bornstein B, Lev T, Gottfried Y, Kemeny S, Garcia-Fernandez M, Kagan J, Larisch S (2012) The IAPantagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo. Cell Death Differ19: 356-368 https://doi.org/10.1038/cdd.2011.112
28	Ellis HM, Horvitz HR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell44: 817-829 https://doi.org/10.1016/0092-8674(86)90004-8
29	Endo K, Kohnoe S, Watanabe A, Tashiro H, Sakata H, Morita M, Kakeji Y, Maehara Y (2009) Clinical significance of Smac/ DIABLO expression in colorectal cancer. Oncol Rep21: 351-355
30	Fischer U, Schulze-Osthoff K (2005) New approaches and therapeutics targeting apoptosis in disease. Pharmacol Rev57: 187-215 https://doi.org/10.1124/pr.57.2.6
31	Fulda S, Vucic D (2012) Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov11: 109-124 https://doi.org/10.1038/nrd3627
32	Fulda S, Wick W, Weller M, Debatin KM (2002) Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med8: 808-815
33	Gao Z, Tian Y, Wang J, Yin Q, Wu H, Li YM, Jiang X (2007) A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/ Diablo. J Biol Chem282: 30718-30727 https://doi.org/10.1074/jbc.M705258200
34	Garcia-Fernandez M, Kissel H, Brown S, Gorenc T, Schile AJ, Rafii S, Larisch S, Steller H (2010) Sept4/ARTS is required for stem cell apoptosis and tumor suppression. Genes Dev24: 2282-2293 https://doi.org/10.1101/gad.1970110
35	Goldstein JC, Waterhouse NJ, Juin P, Evan GI, Green DR (2000) The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant. Nat Cell Biol2: 156-162 https://doi.org/10.1038/35004029
36	Goldstein JC, Munoz-Pinedo C, Ricci JE, Adams SR, Kelekar A, Schuler M, Tsien RY, Green DR (2005) Cytochrome c is released in a single step during apoptosis. Cell Death Differ12: 453-462 https://doi.org/10.1038/sj.cdd.4401596
37	Gottfried Y, Rotem A, Lotan R, Steller H, Larisch S (2004) The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. EMBO J23: 1627-1635 https://doi.org/10.1038/sj.emboj.7600155
38	Goyal L, McCall K, Agapite J, Hartwieg E, Steller H (2000) Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function. EMBO J19: 589-597 https://doi.org/10.1093/emboj/19.4.589
39	Grether ME, Abrams JM, Agapite J, White K, Steller H (1995) The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes Dev9: 1694-1708 https://doi.org/10.1101/gad.9.14.1694
40	Guicciardi ME, Gores GJ (2013) Unshackling caspase-7 for cancer therapy. J Clin Investig123: 3706-3708 https://doi.org/10.1172/JCI71440
41	Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell94: 339-352 https://doi.org/10.1016/S0092-8674(00)81477-4
42	Han J, Zhong CQ, Zhang DW (2011) Programmed necrosis: backup to and competitor with apoptosis in the immune system. Nat Immunol12: 1143-1149 https://doi.org/10.1038/ni.2159
43	Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, Katayama R, Hashimoto C, Zhang X, Noda T (2004) Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol6: 849-860 https://doi.org/10.1038/ncb1159
44	Hao Z, Duncan GS, Chang CC, Elia A, Fang M, Wakeham A, Okada H, Calzascia T, Jang Y, You-Ten A (2005) Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell121: 579-591 https://doi.org/10.1016/j.cell.2005.03.016
45	Hardwick JM, Soane L (2013) Multiple functions of BCL-2 family proteins. Cold Spring Harb Perspect Biol5(2). doi: https://doi.org/10.1101/cshperspect.a008722
46	Harlin H, Reffey SB, Duckett CS, Lindsten T, Thompson CB (2001) Characterization of XIAP-deficient mice. Mol Cell Biol21: 3604-3608 https://doi.org/10.1128/MCB.21.10.3604-3608.2001
47	He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell137: 1100-1111 https://doi.org/10.1016/j.cell.2009.05.021
48	Hegde R, Srinivasula SM, Zhang Z, Wassell R, Mukattash R, Cilenti L, DuBois G, Lazebnik Y, Zervos AS, Fernandes-Alnemri T (2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis proteincaspase interaction. J Biol Chem277: 432-438 https://doi.org/10.1074/jbc.M109721200
49	Herbst RS, Frankel SR (2004) Oblimersen sodium (Genasense bcl-2 antisense oligonucleotide): a rational therapeutic to enhance apoptosis in therapy of lung cancer. Clin Cancer Res10: 4245s-4248s https://doi.org/10.1158/1078-0432.CCR-040018
50	Hetz C, Vitte PA, Bombrun A, Rostovtseva TK, Montessuit S, Hiver A, Schwarz MK, Church DJ, Korsmeyer SJ, Martinou JC (2005) Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia. J Biol Chem280: 42960-42970 https://doi.org/10.1074/jbc.M505843200
51	Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, XavierR J, Yuan J (2008) Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell135: 1311-1323 https://doi.org/10.1016/j.cell.2008.10.044
52	Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature348: 334-336 https://doi.org/10.1038/348334a0
53	Horvitz HR (1999) Genetic control of programmed cell death in the nematode Caenorhabditis elegans. Cancer Res59: 1701s-1706s
54	Horvitz HR, Shaham S, Hengartner MO (1994) The genetics of programmed cell death in the nematode Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol59: 377-385 https://doi.org/10.1101/SQB.1994.059.01.042
55	Hu Y, Ding L, Spencer DM, Nunez G (1998) WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation. J Biol Chem273: 33489-33494 https://doi.org/10.1074/jbc.273.50.33489
56	Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H (2001) Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell104: 781-790
57	Huang H, Zhang XF, Zhou HJ, Xue YH, Dong QZ, Ye QH, Qin LX (2010) Expression and prognostic significance of osteopontin and caspase-3 in hepatocellular carcinoma patients after curative resection. Cancer Sci101: 1314-1319 https://doi.org/10.1111/j.1349-7006.2010.01524.x
58	Jiang X, Wang X (2000) Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J Biol Chem275: 31199-31203 https://doi.org/10.1074/jbc.C000405200
59	Jiang X, Kim HE, Shu H, Zhao Y, Zhang H, Kofron J, Donnelly J, Burns D, Ng SC, Rosenberg S, Wang X (2003) Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway. Science299: 223-226 https://doi.org/10.1126/science.1076807
60	Jiang X, Wang X (2004) Cytochrome C-mediated apoptosis. Annu Rev Biochem73: 87-106 https://doi.org/10.1146/annurev.biochem.73.011303.073706
61	Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC, Bouillet P, Thomas HE, Borner C, Silke J (2009) XIAP discriminates between type I and type II FAS-induced apoptosis. Nature460: 1035-1039 https://doi.org/10.1038/nature08229
62	Kamada S, Shimono A, Shinto Y, Tsujimura T, Takahashi T, Noda T, Kitamura Y, Kondoh H, Tsujimoto Y (1995) bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine. Cancer Res55: 354-359
63	Katagiri N, Shobuike T, Chang B, Kukita A, Miyamoto H (2012) The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila. Microbes Infect14: 1123-1132 https://doi.org/10.1016/j.micinf.2012.03.006
64	Kerr JF (2002) History of the events leading to the formulation of the apoptosis concept. Toxicology181-182: 471-474 https://doi.org/10.1016/S0300-483X(02)00457-2
65	Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer26: 239-257 https://doi.org/10.1038/bjc.1972.33
66	Kim HE, Du F, Fang M, Wang X (2005) Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. Proc Natl Acad Sci USA102: 17545-17550 https://doi.org/10.1073/pnas.0507900102
67	Kim HE, Jiang X, Du F, Wang X (2008) PHAPI, CAS, andHsp70 promote apoptosome formation by preventing Apaf-1 aggregation and enhancing nucleotide exchange on Apaf-1. Mol Cell30: 239-247 https://doi.org/10.1016/j.molcel.2008.03.014
68	Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA (1996) Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature384: 368-372 https://doi.org/10.1038/384368a0
69	Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MS, Rakic P, Flavell RA (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell94: 325-337 https://doi.org/10.1016/S0092-8674(00)81476-2
70	Kuranaga E, Miura M (2007) Nonapoptotic functions of caspases: caspases as regulatory molecules for immunity and cell-fate determination. Trends Cell Biol17: 135-144 https://doi.org/10.1016/j.tcb.2007.01.001
71	LaCasse EC, Baird S, Korneluk RG, MacKenzie AE (1998) The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene17: 3247-3259 https://doi.org/10.1038/sj.onc.1202569
72	Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, Vandenabeele P (2007) Caspases in cell survival, proliferation and differentiation. Cell Death Differ14: 44-55 https://doi.org/10.1038/sj.cdd.4402047
73	Larisch S, Yi Y, Lotan R, Kerner H, Eimerl S, Tony Parks W, Gottfried Y, Birkey Reffey S, de Caestecker MP, Danielpour D (2000) A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol2: 915-921 https://doi.org/10.1038/35046566
74	Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell91: 479-489 https://doi.org/10.1016/S0092-8674(00)80434-1
75	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. Cell94: 491-501 https://doi.org/10.1016/S0092-8674(00)81590-1
76	Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG (2004) A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science305: 1471-1474 https://doi.org/10.1126/science.1098231
77	Li Z, Jo J, Jia JM, Lo SC, Whitcomb DJ, Jiao S, Cho K, Sheng M (2010) Caspase-3 activation via mitochondria is required for longterm depression and AMPA receptor internalization. Cell141: 859-871 https://doi.org/10.1016/j.cell.2010.03.053
78	Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, Damko E, Moquin D, Walz T, McDermott A (2012) The RIP1/ RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell150: 339-350 https://doi.org/10.1016/j.cell.2012.06.019
79	Lieber J, Eicher C, Wenz J, Kirchner B, Warmann SW, Fuchs J, Armeanu-Ebinger S (2011) The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma. BMC Cancer11: 362 https://doi.org/10.1186/1471-2407-11-362
80	Lindsten T, Ross AJ, King A, Zong WX, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth K (2000) The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell6: 1389-1399 https://doi.org/10.1016/S1097-2765(00)00136-2
81	Linkermann A, Green DR (2014) Necroptosis. N Engl J Med370: 455-465 https://doi.org/10.1056/NEJMra1310050
82	Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell86: 147-157 https://doi.org/10.1016/S0092-8674(00)80085-9
83	Liu Z, Sun C, Olejniczak ET, Meadows RP, Betz SF, Oost T, Herrmann J, Wu JC, Fesik SW (2000) Structural basis for binding of Smac/ DIABLO to the XIAP BIR3 domain. Nature408: 1004-1008 https://doi.org/10.1038/35050006
84	Lu J, Bai L, Sun H, Nikolovska-Coleska Z, McEachern D, Qiu S, Miller RS, Yi H, Shangary S, Sun Y (2008) SM-164: a novel, bivalent Smac mimetic that induces apoptosis and tumor regression by concurrent removal of the blockade of cIAP-1/2 and XIAP. Cancer Res68: 9384-9393 https://doi.org/10.1158/0008-5472.CAN-08-2655
85	Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell94: 481-490 https://doi.org/10.1016/S0092-8674(00)81589-5
86	MacFarlane M, Merrison W, Bratton SB, Cohen GM (2002) Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. J Biol Chem277: 36611-36616 https://doi.org/10.1074/jbc.M200317200
87	Mahadevan D, Chalasani P, Rensvold D, Kurtin S, Pretzinger C, Jolivet J, Ramanathan RK, Von Hoff DD, Weiss GJ (2013) Phase I trial of AEG35156 an antisense oligonucleotide to XIAP plus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. Am J Clin Oncol36: 239-243 https://doi.org/10.1097/COC.0b013e3182467a13
88	Martins LM, Iaccarino I, Tenev T, Gschmeissner S, Totty NF, Lemoine NR, Savopoulos J, Gray CW, Creasy CL, Dingwall C (2002) The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem277: 439-444 https://doi.org/10.1074/jbc.M109784200
89	Martins LM, Morrison A, Klupsch K, Fedele V, Moisoi N, Teismann P, Abuin A, Grau E, Geppert M, Livi GP (2004) Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice. Mol Cell Biol24: 9848-9862 https://doi.org/10.1128/MCB.24.22.9848-9862.2004
90	Martins CP, Brown-Swigart L, Evan GI (2006) Modeling the therapeutic efficacy of p53 restoration in tumors. Cell127: 1323-1334 https://doi.org/10.1016/j.cell.2006.12.007
91	McIlwain DR, Berger T, Mak TW (2013) Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol5: a008656 https://doi.org/10.1101/cshperspect.a008656
92	Michaelidis TM, Sendtner M, Cooper JD, Airaksinen MS, Holtmann B, Meyer M, Thoenen H (1996) Inactivation of bcl-2 results in progressive degeneration of motoneurons, sympathetic and sensory neurons during early postnatal development. Neuron17: 75-89 https://doi.org/10.1016/S0896-6273(00)80282-2
93	Mizutani Y, Nakanishi H, Li YN, Matsubara H, Yamamoto K, Sato N, Shiraishi T, Nakamura T, Mikami K, Okihara K (2007) Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis. Int J Oncol30: 919-925
94	Motoyama N, Wang F, Roth KA, Sawa H, Nakayama K, Negishi I, Senju S, Zhang Q, Fujii S (1995) Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science267: 1506-1510 https://doi.org/10.1126/science.7878471
95	Motoyama N, Kimura T, Takahashi T, Watanabe T, Nakano T (1999) bcl-x prevents apoptotic cell death of both primitive and definitive erythrocytes at the end of maturation. J Exp Med189: 1691-1698 https://doi.org/10.1084/jem.189.11.1691
96	Moulin M, Anderton H, Voss AK, Thomas T, Wong WW, Bankovacki A, Feltham R, Chau D, Cook WD, Silke J (2012) IAPs limit activation of RIP kinases by TNF receptor 1 during development. EMBO J31: 1679-1691 https://doi.org/10.1038/emboj.2012.18
97	Newton K, Dugger DL, Wickliffe KE, Kapoor N, de Almagro MC, Vucic D, Komuves L, Ferrando RE, French DM, Webster J (2014) Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science343: 1357-1360 https://doi.org/10.1126/science.1249361
98	Nikolaev A, McLaughlin T, O’Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature457: 981-989 https://doi.org/10.1038/nature07767
99	Oberst A, Dillon CP, Weinlich R, McCormick LL, Fitzgerald P, Pop C, Hakem R, Salvesen GS, Green DR (2011) Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature471: 363-367 https://doi.org/10.1038/nature09852
100	Okada H, Suh WK, Jin J, Woo M, Du C, Elia A, Duncan GS, Wakeham A, Itie A, Lowe SW (2002) Generation and characterization of Smac/DIABLO-deficient mice. Mol Cell Biol22: 3509-3517 https://doi.org/10.1128/MCB.22.10.3509-3517.2002
101	Okada H, Bakal C, Shahinian A, Elia A, Wakeham A, Suh WK, Duncan GS, Ciofani M, Rottapel R, Zuniga-Pflucker JC (2004) Survivin loss in thymocytes triggers p53-mediated growth arrest and p53-independent cell death. J Exp Med199: 399-410 https://doi.org/10.1084/jem.20032092
102	Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas.[see comment]. Nature358: 80-83 https://doi.org/10.1038/358080a0
103	Popgeorgiev N, Bonneau B, Ferri KF, Prudent J, Thibaut J, Gillet G (2011) The apoptotic regulator Nrz controls cytoskeletal dynamics via the regulation of Ca2+ trafficking in the zebrafish blastula. Dev Cell20: 663-676 https://doi.org/10.1016/j.devcel.2011.03.016
104	Provencio M, Martin P, Garcia V, Candia A, Sanchez AC, Bellas C (2010) Caspase 3a: new prognostic marker for diffuse large B-cell lymphoma in the rituximab era. Leuk Lymphoma51: 2021-2030 https://doi.org/10.3109/10428194.2010.516039
105	Ren J, Shi M, Liu R, Yang QH, Johnson T, Skarnes WC, Du C (2005) The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development. Proc Natl Acad Sci USA102: 565-570 https://doi.org/10.1073/pnas.0408744102
106	Ren D, Tu HC, Kim H, Wang GX, Bean GR, Takeuchi O, Jeffers JR, Zambetti GP, Hsieh JJ, Cheng EH (2010) BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science330: 1390-1393 https://doi.org/10.1126/science.1190217
107	Reuland SN, Goldstein NB, Partyka KA, Cooper DA, Fujita M, Norris DA, Shellman YG (2011) The combination of BH3-mimetic ABT-737 with the alkylating agent temozolomide induces strong synergistic killing of melanoma cells independent of p53. PloS One6: e24294 https://doi.org/10.1371/journal.pone.0024294
108	Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y (2005) Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature434: 926-933 https://doi.org/10.1038/nature03465
109	Rodriguez J, Lazebnik Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev13: 3179-3184 https://doi.org/10.1101/gad.13.24.3179
110	Rolland SG, Conradt B (2010) New role of the BCL2 family of proteins in the regulation of mitochondrial dynamics. Curr Opin Cell Biol22: 852-858 https://doi.org/10.1016/j.ceb.2010.07.014
111	Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. Embo J16: 6914-6925 https://doi.org/10.1093/emboj/16.23.6914
112	Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME (1998) Two CD95 (APO-1/ Fas) signaling pathways. EMBO J17: 1675-1687 https://doi.org/10.1093/emboj/17.6.1675
113	Schimmer AD, Estey EH, Borthakur G, Carter BZ, Schiller GJ, Tallman MS, Altman JK, Karp JE, Kassis J, Hedley DW (2009) Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia. J Clin Oncol27: 4741-4746 https://doi.org/10.1200/JCO.2009.21.8172
114	Selivanova G, Iotsova V, Okan I, Fritsche M, Strom M, Groner B, Grafstrom RC, Wiman KG (1997) Restoration of the growth suppression function of mutant p53 by a synthetic peptide derived from the p53 C-terminal domain. Nat Med3: 632-638 https://doi.org/10.1038/nm0697-632
115	Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska Z, Ding K, Wang G, Chen J (2008) Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci USA105: 3933-3938 https://doi.org/10.1073/pnas.0708917105
116	Shchors K, Persson AI, Rostker F, Tihan T, Lyubynska N, Li N, Swigart LB, Berger MS, Hanahan D, Weiss WA (2013) Using a preclinicalmousemodel of high-grade astrocytomato optimize p53 restoration therapy. Proc Natl Acad Sci USA110: E1480-E1489 https://doi.org/10.1073/pnas.1219142110
117	Skoufias DA, Mollinari C, Lacroix FB, Margolis RL (2000) Human survivin is a kinetochore-associated passenger protein. J Cell Biol151: 1575-1582 https://doi.org/10.1083/jcb.151.7.1575
118	Speliotes EK, Uren A, Vaux D, Horvitz HR (2000) The survivin-like C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone. Mol Cell6: 211-223 https://doi.org/10.1016/S1097-2765(00)00023-X
119	Steinhart L, Belz K, Fulda S (2013) Smac mimetic and demethylating agents synergistically trigger cell death in acute myeloid leukemia cells and overcome apoptosis resistance by inducing necroptosis. Cell Death Dis4: e802 https://doi.org/10.1038/cddis.2013.320
120	Strater J, Herter I, Merkel G, Hinz U, Weitz J, Moller P (2010) Expression and prognostic significance of APAF-1, caspase-8 and caspase-9 in stage II/III colon carcinoma: caspase-8 and caspase-9 is associated with poor prognosis. Int J Cancer127: 873-880
121	Sun XM, Bratton SB, Butterworth M, MacFarlane M, Cohen GM (2002) Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/DIABLO and subsequent inactivation of X-linked inhibitor-of-apoptosis protein. J Biol Chem277: 11345-11351 https://doi.org/10.1074/jbc.M109893200
122	Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell148: 213-227 https://doi.org/10.1016/j.cell.2011.11.031
123	Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell8: 613-621 https://doi.org/10.1016/S1097-2765(01)00341-0
124	Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol11: 621-632 https://doi.org/10.1038/nrm2952
125	Tait SW, Parsons MJ, Llambi F, Bouchier-Hayes L, Connell S, Munoz-Pinedo C, Green DR (2010) Resistance to caspaseindependent cell death requires persistence of intact mitochondria. Dev Cell18: 802-813 https://doi.org/10.1016/j.devcel.2010.03.014
126	Tamm I, Kornblau SM, Segall H, Krajewski S, Welsh K, Kitada S, Scudiero DA, Tudor G, Qui YH, Monks A (2000) Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res6: 1796-1803
127	Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol9: 231-241 https://doi.org/10.1038/nrm2312
128	Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science281: 1312-1316 https://doi.org/10.1126/science.281.5381.1312
129	Toledo F, Wahl GM (2007) MDM2 and MDM4: p53 regulators as targets in anticancer therapy. Int J Biochem Cell Biol39: 1476-1482 https://doi.org/10.1016/j.biocel.2007.03.022
130	Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, Johnson EF, Marsh KC, Mitten MJ, Nimmer P (2008) ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res68: 3421-3428 https://doi.org/10.1158/0008-5472.CAN-07-5836
131	Tsujimoto Y, Cossman J, Jaffe E, Croce CM (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science228: 1440-1443 https://doi.org/10.1126/science.3874430
132	Twiddy D, Cain K (2007) Caspase-9 cleavage, do you need it? Biochem J405: e1-e2
133	Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH (2000) Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol10: 1319-1328 https://doi.org/10.1016/S0960-9822(00)00769-7
134	van Loo G, van Gurp M, Depuydt B, Srinivasula SM, Rodriguez I, Alnemri ES, Gevaert K, Vandekerckhove J, Declercq W, Vandenabeele P (2002) The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ9: 20-26 https://doi.org/10.1038/sj.cdd.4400970
135	Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science303: 844-848 https://doi.org/10.1126/science.1092472
136	Vaux DL, Cory S, Adams JM (1988) Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature335: 440-442 https://doi.org/10.1038/335440a0
137	Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T (2007) Restoration of p53 function leads to tumour regression in vivo. Nature445: 661-665 https://doi.org/10.1038/nature05541
138	Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell102: 43-53 https://doi.org/10.1016/S0092-8674(00)00009-X
139	Verhagen AM, Silke J, Ekert PG, Pakusch M, Kaufmann H, Connolly LM, Day CL, Tikoo A, Burke R, Wrobel C (2002) HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem277: 445-454 https://doi.org/10.1074/jbc.M109891200
140	Villunger A, Labi V, Bouillet P, Adams J, Strasser A (2011) Can the analysis of BH3-only protein knockout mice clarify the issue of ‘direct versus indirect’ activation of Bax and Bak? Cell Death Differ18: 1545-1546 https://doi.org/10.1038/cdd.2011.100
141	Vucic D, Kaiser WJ, Harvey AJ, Miller LK (1997) Inhibition of reaperinduced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs). Proc Natl Acad Sci USA94: 10183-10188 https://doi.org/10.1073/pnas.94.19.10183
142	Vucic D, Kaiser WJ, Miller LK (1998) Inhibitor of apoptosis proteins physically interact with and block apoptosis induced by Drosophila proteins HID and GRIM. Mol Cell Biol18: 3300-3309
143	Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM (2000) ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol10: 1359-1366 https://doi.org/10.1016/S0960-9822(00)00781-8
144	Wade M, Wang YV, Wahl GM (2010) The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol20: 299-309 https://doi.org/10.1016/j.tcb.2010.01.009
145	Wang SL, Hawkins CJ, Yoo SJ, Muller HA, Hay BA (1999) The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell98: 453-463 https://doi.org/10.1016/S0092-8674(00)81974-1
146	Wang Y, Suh YA, Fuller MY, Jackson JG, Xiong S, Terzian T, Quintas-Cardama A, Bankson JA, El-Naggar AK, Lozano G (2011) Restoring expression of wild-type p53 suppresses tumor growth but does not cause tumor regression in mice with a p53 missense mutation. J Clin Investig121: 893-904 https://doi.org/10.1172/JCI44504
147	Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science292: 727-730 https://doi.org/10.1126/science.1059108
148	White K, Tahaoglu E, Steller H (1996) Cell killing by the Drosophila gene reaper. Science271: 805-807 https://doi.org/10.1126/science.271.5250.805
149	Woo M, Hakem R, Soengas MS, Duncan GS, Shahinian A, Kagi D, Hakem A, McCurrach M, Khoo W, Kaufman SA (1998) Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev12: 806-819 https://doi.org/10.1101/gad.12.6.806
150	Woo M, Hakem R, Furlonger C, Hakem A, Duncan GS, Sasaki T, Bouchard D, Lu L, Wu GE, Paige CJ (2003) Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Nat Immunol4: 1016-1022 https://doi.org/10.1038/ni976
151	Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X, Shi Y (2000) Structural basis of IAP recognition by Smac/DIABLO. Nature408: 1008-1012 https://doi.org/10.1038/35050012
152	Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW (2007) Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature445: 656-660 https://doi.org/10.1038/nature05529
153	Yang QH, Du C (2004) Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells. J Biol Chem279: 16963-16970 https://doi.org/10.1074/jbc.M401253200
154	Yang QH, Church-Hajduk R, Ren J, Newton ML, Du C (2003) Omi/ HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis. Genes Dev17: 1487-1496 https://doi.org/10.1101/gad.1097903
155	Yin XM, Wang K, Gross A, Zhao Y, Zinkel S, Klocke B, Roth KA, Korsmeyer SJ (1999) Bid-deficient mice are resistant to Fasinduced hepatocellular apoptosis. Nature400: 886-891 https://doi.org/10.1038/23730
156	Yoshida H, Kong YY, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW (1998) Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell94: 739-750 https://doi.org/10.1016/S0092-8674(00)81733-X
157	Yu T, Wang X, Purring-Koch C, Wei Y, McLendon GL (2001) A mutational epitope for cytochrome C binding to the apoptosis protease activation factor-1. J Biol Chem276: 13034-13038 https://doi.org/10.1074/jbc.M009773200
158	Yu X, Vazquez A, Levine AJ, Carpizo DR (2012) Allele-specific p53 mutant reactivation. Cancer Cell21: 614-625 https://doi.org/10.1016/j.ccr.2012.03.042
159	Zermati Y, Garrido C, Amsellem S, Fishelson S, Bouscary D, Valens F, Varet B, Solary E, Hermine O (2001) Caspase activation is required for terminal erythroid differentiation. J Exp Med193: 247-254 https://doi.org/10.1084/jem.193.2.247
160	Zermati Y, Mouhamad S, Stergiou L, Besse B, Galluzzi L, Boehrer S, Pauleau AL, Rosselli F, D’Amelio M, Amendola R (2007) Nonapoptotic role for Apaf-1 in the DNA damage checkpoint: 624-637 https://doi.org/10.1016/j.molcel.2007.09.030
161	Zhang HZ, Kasibhatla S, Wang Y, Herich J, Guastella J, Tseng B, Drewe J, Cai SX (2004) Discovery, characterization and SAR of gambogic acid as a potent apoptosis inducer by a HTS assay. Bioorg Med Chem12: 309-317 https://doi.org/10.1016/j.bmc.2003.11.013
162	Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009) RIP3, an energy metabolism regulator that switches TNFinduced cell death from apoptosis to necrosis. Science325: 332-336 https://doi.org/10.1126/science.1172308
163	Zlobec I, Steele R, Terracciano L, Jass JR, Lugli A (2007) Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol60: 1112-1116 https://doi.org/10.1136/jcp.2006.044537
164	Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell90: 405-413 https://doi.org/10.1016/S0092-8674(00)80501-2
165	Zou H, Li Y, Liu X, Wang X (1999) An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem274: 11549-11556 https://doi.org/10.1074/jbc.274.17.11549
166	Zou H, Yang R, Hao J, Wang J, Sun C, Fesik SW, Wu JC, Tomaselli KJ, Armstrong RC (2003) Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP. J Biol Chem278: 8091-8098 https://doi.org/10.1074/jbc.M204783200

[1]	Anna Gortat,Mónica Sancho,Laura Mondragón,Àgel Messeguer,Enrique Pérez-Payá,Mar Orzáez. Apaf1 inhibition promotes cell recovery from apoptosis[J]. Protein Cell, 2015, 6(11): 833-843.

Viewed

Full text

Abstract

Cited

Shared

Discussed