Intrinsic Pathway for Apoptosis (Homo sapiens)

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24, 34, 364, 4037142017, 181, 14, 19, 33, 41...21621, 19, 25, 41, 4241391020, 28, 40191021922155, 7, 2738262531617, 182210, 30298, 12, 35, 4326422515, 22, 32, 4120, 28, 40113738active caspase-8 mitochondrial inner membrane14-3-3 eta dimer mitochondrial outer membraneYWHAB dimer YWHAE dimer BADBCL-2 tBID bound to inactive BAX Calcineurin B complex 14-3-3 theta dimer Apaf-1Cytochrome C DP-1E2F1 complex Cleaved Caspase-9 active caspase-3 tBIDBCL-2 active caspase-7 active caspase-3 BIM sequestered to dynein 14-3-3 gamma dimer Bcl-XL interacting BH3-only proteins 14-3-3 dimer SMACXIAP cytosolXIAPCaspase-7 Cleaved Caspase-9 tBID bound to inactive BAK BMF sequestered to dynein 14-3-3 proteinsp-S99-BAD complex Dynein Active oligomeric BAK XIAPCaspase-3 SMACXIAPCaspase-9 Cytochrome CApaf-1ATPProcaspase-9 XIAPCaspase-3 Cleaved Caspase-9 Apaf-1Cytochrome C XIAPCaspase-7 SMACXIAPCaspase-3 14-3-3 theta dimer 14-3-3 dimer Bcl-XLBH3-only protein complex 14-3-3zeta dimer 14-3-3 gamma dimer 14-3-3 eta dimer Activated BAX Bcl2BH3-only protein complex XIAPCaspase-9 Apoptosome 14-3-3zeta dimer YWHAB dimer Cleaved Caspase-9 Apaf-1Cytochrome C Dynein YWHAE dimer active caspase-7 SMACXIAPCaspase-7 XIAPCaspase-9 active caspase-7 Caspase-8 dimer 14-3-3 sigma dimer active caspase-3 14-3-3 sigma dimer PMAIP1 SMACXIAPCaspase-3CASP3YWHAQ DIABLOE2F1 CASP7BAK1CASP9 CASP3YWHAZ APAF1 XIAPCaspase-7Bcl-XL interacting BH3-only proteinstBID bound to inactive BAKBAXCASP9APAF1YWHAGBAX activatedBIDp-S99-BADBCL2 APAF1 CASP3ATPBAX tBID bound to inactive BAXSFN YWHAH BAK1 ATP CASP7ATP14-3-3 proteinsp-S99-BAD complexCYCS BCL2L1 ADPBIDBAK1 activated DYNLL1 CASP9 CASP9XIAPCaspase-9YWHAGYWHAE CASP8MYS-BIDCASP3BMF BIDCYCSH2OXIAPCaspase-3Apaf-1Cytochrome CBBC3 BADBIDCASP9YWHAQ ADPCASP3Calcineurin B complexPPP3R1 DIABLOactive caspase-3Cleaved Caspase-9SFN BAK1 activatedXIAP CASP3DYNLL2 CASP9BMF sequestered to dynein Active AKTCYCS CYCSSMACXIAPSMACXIAPCaspase-9SMACXIAPCaspase-7YWHABp-S99-BAD BAXBBC3p-BMFBAX 14-3-3 dimerPIP3 activates AKT signalingp-BCL2L11NMT1Cytochrome CApaf-1ATPProcaspase-9YWHABCASP7CYCS BAD YWHAE PiActivated BAXDP-1E2F1 complexp-S15-TP53BCL2CASP9 BIM sequestered to dynein XIAP BIDCASP3Dynein active caspase-8PMAIP1CASP7BAD GZMBMAPK8TFDP1DYNLL1 CASP8active caspase-7ApoptosomeYWHAH p-BMFCASP9p-BCL2L11CASP9 XIAP Bcl2BH3-only protein complexBcl-2 interacting BH-3 only proteinsBBC3BADDYNLL2 BCL2L1XIAP p-BCL2L11 DIABLO CASP7BCL2 APAF1 DIABLO tBIDBCL-2Dynein CASP9BCL2 XIAP PMAIP1Bcl-XLBH3-only protein complexXIAP DIABLO ADPCASP7BIDPPP3CC YWHAZ XIAP DIABLO BIDATPADPATPActive oligomeric BAKBADBCL-2BCL2L11 CASP7261313261323, 3113131313


Description

The intrinsic (Bcl-2 inhibitable or mitochondrial) pathway of apoptosis functions in response to various types of intracellular stress including growth factor withdrawal, DNA damage, unfolding stresses in the endoplasmic reticulum and death receptor stimulation. Following the reception of stress signals, proapoptotic BCL-2 family proteins are activated and subsequently interact with and inactivate antiapoptotic BCL-2 proteins. This interaction leads to the destabilization of the mitochondrial membrane and release of apoptotic factors. These factors induce the caspase proteolytic cascade, chromatin condensation, and DNA fragmentation, ultimately leading to cell death. The key players in the Intrinsic pathway are the Bcl-2 family of proteins that are critical death regulators residing immediately upstream of mitochondria. The Bcl-2 family consists of both anti- and proapoptotic members that possess conserved alpha-helices with sequence conservation clustered in BCL-2 Homology (BH) domains. Proapoptotic members are organized as follows:

1. "Multidomain" BAX family proteins such as BAX, BAK etc. that display sequence conservation in their BH1-3 regions. These proteins act downstream in mitochondrial disruption. <p> 2. "BH3-only" proteins such as BID,BAD, NOXA, PUMA,BIM, and BMF have only the short BH3 motif. These act upstream in the pathway, detecting developmental death cues or intracellular damage. Anti-apoptotic members like Bcl-2, Bcl-XL and their relatives exhibit homology in all segments BH1-4. One of the critical functions of BCL-2/BCL-XL proteins is to maintain the integrity of the mitochondrial outer membrane. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=109606</div>

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Bibliography

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  1. Chen XQ, Fung YW, Yu AC.; ''Association of 14-3-3gamma and phosphorylated bad attenuates injury in ischemic astrocytes.''; PubMed Europe PMC Scholia
  2. Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM.; ''ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas.''; PubMed Europe PMC Scholia
  3. Paulsen M, Ussat S, Jakob M, Scherer G, Lepenies I, Schütze S, Kabelitz D, Adam-Klages S.; ''Interaction with XIAP prevents full caspase-3/-7 activation in proliferating human T lymphocytes.''; PubMed Europe PMC Scholia
  4. Hu Q, Wu D, Chen W, Yan Z, Yan C, He T, Liang Q, Shi Y.; ''Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome.''; PubMed Europe PMC Scholia
  5. Shiozaki EN, Chai J, Rigotti DJ, Riedl SJ, Li P, Srinivasula SM, Alnemri ES, Fairman R, Shi Y.; ''Mechanism of XIAP-mediated inhibition of caspase-9.''; PubMed Europe PMC Scholia
  6. Du C, Fang M, Li Y, Li L, Wang X.; ''Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.''; PubMed Europe PMC Scholia
  7. Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, Salvesen GS.; ''XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs.''; PubMed Europe PMC Scholia
  8. Blanchard H, Kodandapani L, Mittl PR, Marco SD, Krebs JF, Wu JC, Tomaselli KJ, Grütter MG.; ''The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis.''; PubMed Europe PMC Scholia
  9. Reingewertz TH, Shalev DE, Sukenik S, Blatt O, Rotem-Bamberger S, Lebendiker M, Larisch S, Friedler A.; ''Mechanism of the interaction between the intrinsically disordered C-terminus of the pro-apoptotic ARTS protein and the Bir3 domain of XIAP.''; PubMed Europe PMC Scholia
  10. Cheng TC, Hong C, Akey IV, Yuan S, Akey CW.; ''A near atomic structure of the active human apoptosome.''; PubMed Europe PMC Scholia
  11. Yuan S, Yu X, Topf M, Ludtke SJ, Wang X, Akey CW.; ''Structure of an apoptosome-procaspase-9 CARD complex.''; PubMed Europe PMC Scholia
  12. Denault JB, Békés M, Scott FL, Sexton KM, Bogyo M, Salvesen GS.; ''Engineered hybrid dimers: tracking the activation pathway of caspase-7.''; PubMed Europe PMC Scholia
  13. Wang L, Xing H, Tian Z, Peng L, Li Y, Tang K, Rao Q, Wang M, Wang J.; ''iASPPsv antagonizes apoptosis induced by chemotherapeutic agents in MCF-7 cells and mouse thymocytes.''; PubMed Europe PMC Scholia
  14. Li CQ, Robles AI, Hanigan CL, Hofseth LJ, Trudel LJ, Harris CC, Wogan GN.; ''Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53.''; PubMed Europe PMC Scholia
  15. Bhattacharya S, Ray RM, Johnson LR.; ''STAT3-mediated transcription of Bcl-2, Mcl-1 and c-IAP2 prevents apoptosis in polyamine-depleted cells.''; PubMed Europe PMC Scholia
  16. Bornstein B, Gottfried Y, Edison N, Shekhtman A, Lev T, Glaser F, Larisch S.; ''ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a mechanism that is different from other IAP-antagonists.''; PubMed Europe PMC Scholia
  17. Arnoult D, Gaume B, Karbowski M, Sharpe JC, Cecconi F, Youle RJ.; ''Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax/Bak-mediated permeabilization.''; PubMed Europe PMC Scholia
  18. Gottfried Y, Rotem A, Lotan R, Steller H, Larisch S.; ''The mitochondrial ARTS protein promotes apoptosis through targeting XIAP.''; PubMed Europe PMC Scholia
  19. Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC, Strasser A.; ''Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis.''; PubMed Europe PMC Scholia
  20. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N.; ''Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.''; PubMed Europe PMC Scholia
  21. Zou H, Li Y, Liu X, Wang X.; ''An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.''; PubMed Europe PMC Scholia
  22. Larisch S, Yi Y, Lotan R, Kerner H, Eimerl S, Tony Parks W, Gottfried Y, Birkey Reffey S, de Caestecker MP, Danielpour D, Book-Melamed N, Timberg R, Duckett CS, Lechleider RJ, Steller H, Orly J, Kim SJ, Roberts AB.; ''A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif.''; PubMed Europe PMC Scholia
  23. Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee RA, Robbins PD, Fernandes-Alnemri T, Shi Y, Alnemri ES.; ''A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.''; PubMed Europe PMC Scholia
  24. Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC.; ''Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD.''; PubMed Europe PMC Scholia
  25. Nakano K, Vousden KH.; ''PUMA, a novel proapoptotic gene, is induced by p53.''; PubMed Europe PMC Scholia
  26. Eskes R, Desagher S, Antonsson B, Martinou JC.; ''Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane.''; PubMed Europe PMC Scholia
  27. Lei K, Davis RJ.; ''JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis.''; PubMed Europe PMC Scholia
  28. Patel S, George R, Autore F, Fraternali F, Ladbury JE, Nikolova PV.; ''Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax.''; PubMed Europe PMC Scholia
  29. Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H.; ''Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain.''; PubMed Europe PMC Scholia
  30. Hershko T, Ginsberg D.; ''Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis.''; PubMed Europe PMC Scholia
  31. Yuan S, Topf M, Reubold TF, Eschenburg S, Akey CW.; ''Changes in Apaf-1 conformation that drive apoptosome assembly.''; PubMed Europe PMC Scholia
  32. Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y.; ''Structural and biochemical basis of apoptotic activation by Smac/DIABLO.''; PubMed Europe PMC Scholia
  33. Denault JB, Salvesen GS.; ''Human caspase-7 activity and regulation by its N-terminal peptide.''; PubMed Europe PMC Scholia
  34. Bellosillo B, Villamor N, López-Guillermo A, Marcé S, Bosch F, Campo E, Montserrat E, Colomer D.; ''Spontaneous and drug-induced apoptosis is mediated by conformational changes of Bax and Bak in B-cell chronic lymphocytic leukemia.''; PubMed Europe PMC Scholia
  35. Itahana K, Zhang Y.; ''Mitochondrial p32 is a critical mediator of ARF-induced apoptosis.''; PubMed Europe PMC Scholia
  36. Watt W, Koeplinger KA, Mildner AM, Heinrikson RL, Tomasselli AG, Watenpaugh KD.; ''The atomic-resolution structure of human caspase-8, a key activator of apoptosis.''; PubMed Europe PMC Scholia
  37. Chai J, Wu Q, Shiozaki E, Srinivasula SM, Alnemri ES, Shi Y.; ''Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding.''; PubMed Europe PMC Scholia
  38. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ.; ''Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner.''; PubMed Europe PMC Scholia
  39. Chau BN, Cheng EH, Kerr DA, Hardwick JM.; ''Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1.''; PubMed Europe PMC Scholia
  40. Deveraux QL, Takahashi R, Salvesen GS, Reed JC.; ''X-linked IAP is a direct inhibitor of cell-death proteases.''; PubMed Europe PMC Scholia
  41. Han J, Flemington C, Houghton AB, Gu Z, Zambetti GP, Lutz RJ, Zhu L, Chittenden T.; ''Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals.''; PubMed Europe PMC Scholia
  42. Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X, Shi Y.; ''Structural basis of IAP recognition by Smac/DIABLO.''; PubMed Europe PMC Scholia
  43. Ruffolo SC, Shore GC.; ''BCL-2 selectively interacts with the BID-induced open conformer of BAK, inhibiting BAK auto-oligomerization.''; PubMed Europe PMC Scholia
  44. Fischer B, Coelho D, Dufour P, Bergerat JP, Denis JM, Gueulette J, Bischoff P.; ''Caspase 8-mediated cleavage of the pro-apoptotic BCL-2 family member BID in p53-dependent apoptosis.''; PubMed Europe PMC Scholia
  45. Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y.; ''Structural basis of caspase-7 inhibition by XIAP.''; PubMed Europe PMC Scholia
  46. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X.; ''Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3.''; PubMed Europe PMC Scholia
  47. Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ.; ''Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death.''; PubMed Europe PMC Scholia
  48. Abhari BA, Davoodi J.; ''A mechanistic insight into SMAC peptide interference with XIAP-Bir2 inhibition of executioner caspases.''; PubMed Europe PMC Scholia
  49. Bratton SB, Walker G, Srinivasula SM, Sun XM, Butterworth M, Alnemri ES, Cohen GM.; ''Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes.''; PubMed Europe PMC Scholia
  50. Subramanian RR, Masters SC, Zhang H, Fu H.; ''Functional conservation of 14-3-3 isoforms in inhibiting bad-induced apoptosis.''; PubMed Europe PMC Scholia
  51. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X.; ''Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.''; PubMed Europe PMC Scholia
  52. Won J, Kim DY, La M, Kim D, Meadows GG, Joe CO.; ''Cleavage of 14-3-3 protein by caspase-3 facilitates bad interaction with Bcl-x(L) during apoptosis.''; PubMed Europe PMC Scholia
  53. Pathan N, Marusawa H, Krajewska M, Matsuzawa S, Kim H, Okada K, Torii S, Kitada S, Krajewski S, Welsh K, Pio F, Godzik A, Reed JC.; ''TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer.''; PubMed Europe PMC Scholia
  54. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME.; ''Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.''; PubMed Europe PMC Scholia
  55. Khor TO, Gul YA, Ithnin H, Seow HF.; ''Positive correlation between overexpression of phospho-BAD with phosphorylated Akt at serine 473 but not threonine 308 in colorectal carcinoma.''; PubMed Europe PMC Scholia
  56. Martin MC, Allan LA, Mancini EJ, Clarke PR.; ''The docking interaction of caspase-9 with ERK2 provides a mechanism for the selective inhibitory phosphorylation of caspase-9 at threonine 125.''; PubMed Europe PMC Scholia
  57. Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernández-Luna JL, Nuñez G, Dalton WS, Jove R.; ''Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells.''; PubMed Europe PMC Scholia
  58. Salvesen GS, Duckett CS.; ''IAP proteins: blocking the road to death's door.''; PubMed Europe PMC Scholia
  59. Alimonti JB, Shi L, Baijal PK, Greenberg AH.; ''Granzyme B induces BID-mediated cytochrome c release and mitochondrial permeability transition.''; PubMed Europe PMC Scholia
  60. Renatus M, Stennicke HR, Scott FL, Liddington RC, Salvesen GS.; ''Dimer formation drives the activation of the cell death protease caspase 9.''; PubMed Europe PMC Scholia
  61. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P.; ''Toxic proteins released from mitochondria in cell death.''; PubMed Europe PMC Scholia
  62. Riedl SJ, Fuentes-Prior P, Renatus M, Kairies N, Krapp S, Huber R, Salvesen GS, Bode W.; ''Structural basis for the activation of human procaspase-7.''; PubMed Europe PMC Scholia
  63. Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A.; ''The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex.''; PubMed Europe PMC Scholia
  64. Kashkar H, Haefs C, Shin H, Hamilton-Dutoit SJ, Salvesen GS, Kronke M, Jurgensmeier JM.; ''XIAP-mediated caspase inhibition in Hodgkin's lymphoma-derived B cells.''; PubMed Europe PMC Scholia
  65. del Peso L, González-García M, Page C, Herrera R, Nuñez G.; ''Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt.''; PubMed Europe PMC Scholia
  66. Carpenter RL, Lo HW.; ''STAT3 Target Genes Relevant to Human Cancers.''; PubMed Europe PMC Scholia
  67. Shi Y.; ''Mechanisms of caspase activation and inhibition during apoptosis.''; PubMed Europe PMC Scholia
  68. Antonsson B, Montessuit S, Sanchez B, Martinou JC.; ''Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells.''; PubMed Europe PMC Scholia
  69. Kang W, Hong SH, Lee HM, Kim NY, Lim YC, Le le TM, Lim B, Kim HC, Kim TY, Ashida H, Yokota A, Hah SS, Chun KH, Jung YK, Yang JK.; ''Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme.''; PubMed Europe PMC Scholia
  70. Thomsen ND, Koerber JT, Wells JA.; ''Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation.''; PubMed Europe PMC Scholia
  71. Zha J, Weiler S, Oh KJ, Wei MC, Korsmeyer SJ.; ''Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis.''; PubMed Europe PMC Scholia
  72. Song Z, Yao X, Wu M.; ''Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis.''; PubMed Europe PMC Scholia
  73. Shakeri R, Kheirollahi A, Davoodi J.; ''Apaf-1: Regulation and function in cell death.''; PubMed Europe PMC Scholia
  74. Yang QH, Du C.; ''Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells.''; PubMed Europe PMC Scholia
  75. Wang X.; ''The expanding role of mitochondria in apoptosis.''; PubMed Europe PMC Scholia
  76. Wilson AM, Morquette B, Abdouh M, Unsain N, Barker PA, Feinstein E, Bernier G, Di Polo A.; ''ASPP1/2 regulate p53-dependent death of retinal ganglion cells through PUMA and Fas/CD95 activation in vivo.''; PubMed Europe PMC Scholia
  77. Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, Greenberg ME.; ''14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation.''; PubMed Europe PMC Scholia
  78. Bergamaschi D, Samuels Y, Jin B, Duraisingham S, Crook T, Lu X.; ''ASPP1 and ASPP2: common activators of p53 family members.''; PubMed Europe PMC Scholia
  79. Sakai T, Liu L, Teng X, Mukai-Sakai R, Shimada H, Kaji R, Mitani T, Matsumoto M, Toida K, Ishimura K, Shishido Y, Mak TW, Fukui K.; ''Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis.''; PubMed Europe PMC Scholia
  80. Yi X, Yin XM, Dong Z.; ''Inhibition of Bid-induced apoptosis by Bcl-2. tBid insertion, Bax translocation, and Bax/Bak oligomerization suppressed.''; PubMed Europe PMC Scholia
  81. Kim HE, Du F, Fang M, Wang X.; ''Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1.''; PubMed Europe PMC Scholia
  82. Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB, Korsmeyer SJ.; ''tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c.''; PubMed Europe PMC Scholia
  83. Gao Z, Tian Y, Wang J, Yin Q, Wu H, Li YM, Jiang X.; ''A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/Diablo.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114961view16:48, 25 January 2021ReactomeTeamReactome version 75
113405view11:48, 2 November 2020ReactomeTeamReactome version 74
112608view15:58, 9 October 2020ReactomeTeamReactome version 73
101524view11:39, 1 November 2018ReactomeTeamreactome version 66
101060view21:21, 31 October 2018ReactomeTeamreactome version 65
100591view19:55, 31 October 2018ReactomeTeamreactome version 64
100140view16:40, 31 October 2018ReactomeTeamreactome version 63
99690view15:09, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99278view12:45, 31 October 2018ReactomeTeamreactome version 62
93878view13:42, 16 August 2017ReactomeTeamreactome version 61
93445view11:23, 9 August 2017ReactomeTeamreactome version 61
86537view09:20, 11 July 2016ReactomeTeamreactome version 56
83332view10:48, 18 November 2015ReactomeTeamVersion54
76964view08:24, 17 July 2014ReactomeTeamFixed remaining interactions
76669view12:03, 16 July 2014ReactomeTeamFixed remaining interactions
75997view10:05, 11 June 2014ReactomeTeamRe-fixing comment source
75700view11:04, 10 June 2014ReactomeTeamReactome 48 Update
75056view13:56, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74836view10:06, 30 April 2014ReactomeTeamReactome46
74700view08:46, 30 April 2014ReactomeTeamReactome46
44875view10:02, 6 October 2011MartijnVanIerselOntology Term : 'apoptotic cell death pathway' added !
42060view21:53, 4 March 2011MaintBotAutomatic update
39867view05:53, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
14-3-3 dimerComplexREACT_147925 (Reactome)
14-3-3 proteins p-S99-BAD complexComplexREACT_5737 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
APAF1 ProteinO14727 (Uniprot-TrEMBL)
APAF1ProteinO14727 (Uniprot-TrEMBL)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated BAXComplexREACT_2560 (Reactome)
Active AKTREACT_13319 (Reactome)
Active oligomeric BAKComplexREACT_4956 (Reactome)
Apaf-1 Cytochrome CComplexREACT_4880 (Reactome)
ApoptosomeComplexREACT_3569 (Reactome)
BAD BCL-2ComplexREACT_3232 (Reactome)
BAD ProteinQ92934 (Uniprot-TrEMBL)
BADProteinQ92934 (Uniprot-TrEMBL)
BAK1 ProteinQ16611 (Uniprot-TrEMBL)
BAK1 activated ProteinQ16611 (Uniprot-TrEMBL)
BAK1 activatedProteinQ16611 (Uniprot-TrEMBL)
BAK1ProteinQ16611 (Uniprot-TrEMBL)
BAX ProteinQ07812 (Uniprot-TrEMBL)
BAX activatedProteinQ07812 (Uniprot-TrEMBL)
BAXProteinQ07812 (Uniprot-TrEMBL)
BBC3 ProteinQ9BXH1 (Uniprot-TrEMBL)
BBC3ProteinQ9BXH1 (Uniprot-TrEMBL)
BCL2 ProteinP10415 (Uniprot-TrEMBL)
BCL2L1 ProteinQ07817 (Uniprot-TrEMBL)
BCL2L11 ProteinO43521 (Uniprot-TrEMBL)
BCL2L1ProteinQ07817 (Uniprot-TrEMBL)
BCL2ProteinP10415 (Uniprot-TrEMBL)
BIDProteinP55957 (Uniprot-TrEMBL)
BIM sequestered to dynein ComplexREACT_3567 (Reactome)
BMF ProteinQ96LC9 (Uniprot-TrEMBL)
BMF sequestered to dynein ComplexREACT_3065 (Reactome)
Bcl-2 interacting BH-3 only proteinsProteinREACT_21617 (Reactome)
Bcl-XL BH3-only protein complexComplexREACT_21559 (Reactome)
Bcl-XL interacting BH3-only proteinsProteinREACT_21650 (Reactome)
Bcl2 BH3-only protein complexComplexREACT_21874 (Reactome)
CASP3ProteinP42574 (Uniprot-TrEMBL)
CASP7ProteinP55210 (Uniprot-TrEMBL)
CASP8ProteinQ14790 (Uniprot-TrEMBL)
CASP9 ProteinP55211 (Uniprot-TrEMBL)
CASP9ProteinP55211 (Uniprot-TrEMBL)
CYCS ProteinP99999 (Uniprot-TrEMBL)
CYCSProteinP99999 (Uniprot-TrEMBL)
Calcineurin B complexComplexREACT_4613 (Reactome)
Cleaved Caspase-9ComplexREACT_5782 (Reactome)
Cytochrome C

Apaf-1 ATP

Procaspase-9		ComplexREACT_5647 (Reactome)
DIABLO ProteinQ9NR28 (Uniprot-TrEMBL)
DIABLOProteinQ9NR28 (Uniprot-TrEMBL)
DP-1 E2F1 complexComplexREACT_5400 (Reactome)
DYNLL1 ProteinP63167 (Uniprot-TrEMBL)
DYNLL2 ProteinQ96FJ2 (Uniprot-TrEMBL)
Dynein ComplexREACT_2522 (Reactome)
Dynein ComplexREACT_5554 (Reactome)
E2F1 ProteinQ01094 (Uniprot-TrEMBL)
GZMBProteinP10144 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
MAPK8ProteinP45983 (Uniprot-TrEMBL)
MYS-BIDProteinP55957 (Uniprot-TrEMBL)
NMT1ProteinP30419 (Uniprot-TrEMBL)
PIP3 activates AKT signalingPathwayWP2653 (WikiPathways) Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PMAIP1 ProteinQ13794 (Uniprot-TrEMBL)
PMAIP1ProteinQ13794 (Uniprot-TrEMBL)
PPP3CC ProteinP48454 (Uniprot-TrEMBL)
PPP3R1 ProteinP63098 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
SFN ProteinP31947 (Uniprot-TrEMBL)
SMAC

XIAP

Caspase-3		ComplexREACT_5281 (Reactome)
SMAC

XIAP

Caspase-7		ComplexREACT_3355 (Reactome)
SMAC

XIAP

Caspase-9		ComplexREACT_4472 (Reactome)
SMAC XIAPComplexREACT_5204 (Reactome)
TFDP1ProteinQ14186 (Uniprot-TrEMBL)
XIAP Caspase-3ComplexREACT_2704 (Reactome)
XIAP Caspase-7ComplexREACT_2853 (Reactome)
XIAP Caspase-9ComplexREACT_4334 (Reactome)
XIAP ProteinP98170 (Uniprot-TrEMBL)
YWHABProteinP31946 (Uniprot-TrEMBL)
YWHAE ProteinP62258 (Uniprot-TrEMBL)
YWHAGProteinP61981 (Uniprot-TrEMBL)
YWHAH ProteinQ04917 (Uniprot-TrEMBL)
YWHAQ ProteinP27348 (Uniprot-TrEMBL)
YWHAZ ProteinP63104 (Uniprot-TrEMBL)
active caspase-3ComplexREACT_2467 (Reactome)
active caspase-7ComplexREACT_3366 (Reactome)
active caspase-8ComplexREACT_151128 (Reactome)
p-BCL2L11 ProteinO43521 (Uniprot-TrEMBL)
p-BCL2L11ProteinO43521 (Uniprot-TrEMBL)
p-BMFProteinQ96LC9 (Uniprot-TrEMBL)
p-S15-TP53ProteinP04637 (Uniprot-TrEMBL)
p-S99-BAD ProteinQ92934 (Uniprot-TrEMBL)
p-S99-BADProteinQ92934 (Uniprot-TrEMBL)
tBID BCL-2ComplexREACT_5048 (Reactome)
tBID bound to inactive BAKComplexREACT_6608 (Reactome)
tBID bound to inactive BAXComplexREACT_6691 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
14-3-3 dimerArrowREACT_1663 (Reactome)
14-3-3 dimerREACT_1139 (Reactome)
14-3-3 proteins p-S99-BAD complexREACT_1663 (Reactome)
ADPArrowREACT_12565 (Reactome)
ADPArrowREACT_1460 (Reactome)
ADPArrowREACT_2116 (Reactome)
ADPArrowREACT_2165 (Reactome)
APAF1REACT_1640 (Reactome)
ATPREACT_12565 (Reactome)
ATPREACT_1460 (Reactome)
ATPREACT_2165 (Reactome)
ATPREACT_39 (Reactome)
Active AKTREACT_12565 (Reactome)
Apaf-1 Cytochrome CREACT_39 (Reactome)
ApoptosomeArrowREACT_2116 (Reactome)
ApoptosomeREACT_1460 (Reactome)
ApoptosomeREACT_2165 (Reactome)
BAD BCL-2ArrowREACT_1062 (Reactome)
BADArrowREACT_1663 (Reactome)
BADREACT_1062 (Reactome)
BADREACT_12565 (Reactome)
BAK1 activatedArrowREACT_1424 (Reactome)
BAK1REACT_6153 (Reactome)
BAX activatedArrowREACT_1506 (Reactome)
BAXREACT_6160 (Reactome)
BCL2L1REACT_21278 (Reactome)
BCL2REACT_21389 (Reactome)
BCL2REACT_784 (Reactome)
BIDArrowREACT_1062 (Reactome)
BIDArrowREACT_1424 (Reactome)
BIDArrowREACT_1506 (Reactome)
BIDREACT_6153 (Reactome)
BIDREACT_6160 (Reactome)
BIDREACT_784 (Reactome)
Bcl-2 interacting BH-3 only proteinsREACT_21389 (Reactome)
Bcl-XL interacting BH3-only proteinsREACT_21278 (Reactome)
CASP3REACT_1460 (Reactome)
CASP7REACT_2165 (Reactome)
CASP9REACT_39 (Reactome)
CYCSREACT_1640 (Reactome)
Calcineurin B complexREACT_1663 (Reactome)
Cleaved Caspase-9ArrowREACT_1035 (Reactome)
Cytochrome C

Apaf-1 ATP

Procaspase-9		REACT_2116 (Reactome)
DIABLOREACT_1090 (Reactome)
DIABLOREACT_1312 (Reactome)
DIABLOREACT_2091 (Reactome)
DP-1 E2F1 complexArrowREACT_1872 (Reactome)
DP-1 E2F1 complexArrowREACT_284 (Reactome)
Dynein ArrowREACT_1888 (Reactome)
Dynein ArrowREACT_1981 (Reactome)
GZMBREACT_1610 (Reactome)
H2OREACT_1663 (Reactome)
MAPK8REACT_1888 (Reactome)
MAPK8REACT_1981 (Reactome)
NMT1REACT_1158 (Reactome)
PiArrowREACT_1663 (Reactome)
REACT_1035 (Reactome) Binding of DIABLO (SMAC) to XIAP promotes the release of caspase-9 from XIAP (Du et al. 2000).
REACT_104 (Reactome) It is thought that due to its p53 dependence for expression, PUMA could function as a mediator of p53-induced apoptosis. Newly synthesized PUMA protein translocates to mitochondria and binds to BCL-2 and Bcl-X(L) through a BH3 domain.
REACT_1062 (Reactome) Short peptides representing BAD and BIX were found to bind BCL-2 displacing BID-like BH3 domains that initiate mitochondrial dysfunction.
REACT_1090 (Reactome) At the beginning of this reaction, 1 molecule of 'SMAC', and 1 molecule of 'XIAP:Caspase-3' are present. At the end of this reaction, 1 molecule of 'SMAC:XIAP:Caspase-3' is present.

This reaction takes place in the 'cytosol'.

REACT_1101 (Reactome) Permeabilization of the outer mitochondrial membrane by pro-apoptotic BCL2 family members BAK and BAX allows release of DIABLO (SMAC) from the mitochondrial intermembrane space into the cytosol (Arnoult et al. 2003). Binding of DIABLO (SMAC) to survivin leads to the inhibition of apoptosis (Song et al. 2003).
REACT_1139 (Reactome) 14-3-3 proteins bind BAD phosphorylated by activated AKT on serine residue S99 (corresponds to mouse Bad serine residue S136). Binding of 14-3-3 proteins to p-S99-BAD facilitates subsequent phosphorylation of BAD on serine residue S118 (corresponds to mouse serine S155), which disrupts binding of BAD to BCL2 proteins and promotes cell survival (Datta et al. 2000). Caspase-3 mediated cleavage of 14-3-3 proteins releases BAD and promotes apoptosis (Won et al. 2003). All known 14-3-3 protein isoforms (beta/alpha i.e. YWHAB, gamma i.e. YWHAG, zeta/delta i.e. YWHAZ, epsilon i.e. YWHAE, eta i.e. YWHAH, sigma i.e. SFN and theta i.e. YWHAQ) can interact with BAD and inhibit it (Subramanian et al. 2001, Chen et al. 2005).
REACT_1158 (Reactome) After proteolytic activation, tBID is myristoylated by NMT-1 at an exposed glycine. N-myristoylation may enable the activated tBID to associate with the lipid components of the mitochondrial membrane.
REACT_12565 (Reactome) Activated AKT phosphorylates the BCL-2 family member BAD at serine 99 (corresponds to serine residue S136 of mouse Bad), blocking the BAD-induced cell death (Datta et al. 1997, del Peso et al. 1997, Khor et al. 2004).
REACT_1286 (Reactome) Activated BAX integrates in the outer mitochondrial membrane (Eskes et al. 2000, Antonsson et al. 2001, Bellosillo et al. 2002, Yi et al. 2003).
REACT_1300 (Reactome) Binding of DIABLO (SMAC) to XIAP promotes the liberation of active caspase-3 from its complex with XIAP (Kashkar et al. 2003).
REACT_1312 (Reactome) At the beginning of this reaction, 1 molecule of 'SMAC', and 1 molecule of 'XIAP:Caspase-9' are present. At the end of this reaction, 1 molecule of 'SMAC:XIAP:Caspase-9' is present.

This reaction takes place in the 'cytosol'.

REACT_1320 (Reactome) The caspase 8 -mediated cleavage of cytosolic, inactive p22 BID at internal Asp sites yields a major p15 and minor p13 and p11 fragments. After myristoylation, tBID translocates to mitochondria as an integral membrane protein.
REACT_1370 (Reactome) N-myristoylation targets tBID to the mitochondrial outer membrane (Zha et al. 2000).
REACT_1424 (Reactome) tBID binds to its mitochondrial partner BAK to release cytochrome c. It has been observed in mouse systems that the activated tBID results in an allosteric activation of BAK. Activated BAK induces intramembranous oligomerization leading to a pore for cytochrome c efflux (Wei et al. 2000).
REACT_1460 (Reactome) Caspases-3 and -7 are directly cleaved downstream of caspase-9 in the cytochrome c/Apaf-1-inducible caspase cascade (Slee et al., 1999).
REACT_1506 (Reactome) During certain types of apoptosis, activated tBID (p15) induces a change in conformation of Bax which leads to the unmasking of its NH2-terminal domain. This change in confirmation usually results in the release of cytochrome c from mitochondria.
REACT_1555 (Reactome) TP53 (p53) stimulates the transcription of PUMA (p53 upregulated modulator of apoptosis) (Nakano and Vousden 2001).
REACT_1585 (Reactome) It was observed that cytosolic Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9.
REACT_1610 (Reactome) GZMB (granzyme B) cleaves BID to produce a p15 truncated form of BID (tBID) (Alimonti et al. 2001).
REACT_1640 (Reactome) Cytochrome c released to the cytosol from the mitochonridal intermembrane space binds APAF1 (Apaf-1) (Zou et al. 1997).
REACT_1663 (Reactome) Calcineurin, the Ca2+ activated protein phosphatase, dephosphorylates BAD, promoting dissociation of BAD from 14-3-3 proteins and the translocation of BAD to the outer mitochondrial membrane (Wang et al. 1999).
REACT_1872 (Reactome) E2F1 directly stimulates the transcription of PMAIP1 (NOXA) (Hershko and Ginsberg 2004).
REACT_1888 (Reactome) MAPK8 (JNK) phosphorylates BCL2L11 (BIM) on a DLC-binding motif (DKSTQTP), involved in dynein (DYNLL2 i.e. DLC1) binding and sequestration of BCL2L11 (BIM) to the cytoskeleton. Phosphorylated BCL2L11 dissociates from dynein. Three sites in BCL2L11 match the JNK consensus: S44, T56 and S58 in BCL2L11 isoform BimL (these residues correspond to S104, T116 and S118 in BCL2L11 isoform BimEL), and all sites appear to be phosphorylated by MAPK8 (JNK) both in vitro and in vivo (Lei and Davis 2003).
REACT_1981 (Reactome) MAPK8 (JNK) phosphorylates BMF on a DLC binding motif DKATQTLSP involved in interaction with dynein DYNLL2 (DLC2), which sequesters BMF to the cytoskeleton. Phosphorylated BMF dissociates from dynein. Two JNK consensus sites exist in BMF: S74 and S77 (Lei and Davis 2003).
REACT_2046 (Reactome) Dephosphorylated BAD translocates to the outer mitochondrial membrane (Wang et al. 1999).
REACT_2091 (Reactome) At the beginning of this reaction, 1 molecule of 'XIAP:Caspase-7', and 1 molecule of 'SMAC' are present. At the end of this reaction, 1 molecule of 'SMAC:XIAP:Caspase-7' is present.

This reaction takes place in the 'cytosol'.

REACT_2102 (Reactome) Binding of DIABLO (SMAC) to the BIR2 domain of XIAP competes with binding of caspase-7 to the same domain of BIR2. As DIABLO has a higher affinity for the BIR2 domain than caspase-7, DIABLO (SMAC) binding to XIAP results in the liberation of caspase-7 (Huang et al. 2001).
REACT_2116 (Reactome) Caspase-9 is activated in an ATP-dependent manner following association with Apaf-1 and cytochrome c (Li et al., 1997)
REACT_21278 (Reactome) BH3-only proteins (tBid, BIM, PUMA, BAD, NOXA) associate with and inactivate anti-apoptotic protein Bcl-XL( Yi et al., 2003; Puthalakath et al., 1999; Nakano and Vousden, 2001; Wang et al., 1999; Oda et al., 2000). The interactions of NOXA with Bcl-XL are inferred from experiments performed in mice (Oda et al., 2000).
REACT_21389 (Reactome) Bcl-2 interacts with tBid (Yi et al. 2003), BIM (Puthalakath et al. 1999), PUMA (Nakano and Vousden 2001), NOXA (Oda et al. 2000), BAD (Yang et al. 2005), BMF (Puthalakath et al. 2001), resulting in inactivation of BCL2.
REACT_2165 (Reactome) Caspases-3 and -7 are directly cleaved downstream of caspase-9 in the cytochrome c/Apaf-1-inducible caspase cascade (Slee et al., 1999).
REACT_2201 (Reactome) TP53 (p53) stimulates transcription of PMAIP1 (NOXA) in response to nitric oxide (Li et al. 2004).
REACT_284 (Reactome) E2F1 directly stimulates the transcription of PUMA (Hershko and Ginsberg 2004).
REACT_341 (Reactome) Once integrated in the outer mitochondrial membrane, BAX forms oligomeric complexes which play an important role in cytochrome C release (Antonsson et al. 2001)
REACT_39 (Reactome) Apaf-1 and Caspase-9 form a complex in the presence of dATP and cytochrome c (Li et al.,1997).
REACT_507 (Reactome) Once activated BAK insterts in the outer mitochondrial membrane, it oligomerizes and these oligomeric BAK complexes are important for the cytochrome C efflux (Ruffolo and Shore 2003).
REACT_535 (Reactome) Permeabilization of the outer mitochondrial membrane by pro-apoptotic BCL2 family proteins, such as BAK and BAX, allows cytochrome c eflux from the mitochondrial intermembrane space into the cytosol (Arnoult et al. 2003).
REACT_600 (Reactome) Once BMF dissociates from the cytoskeleton, it translocates to the outer mitochondrial membrane where it binds BCL2 (Puthalakath et al. 2001).
REACT_6153 (Reactome) tBID binds to its mitochondrial partner BAK to release cytochrome c. It has been observed in mouse systems that the activated tBID results in an allosteric activation of BAK. Activated BAK induces intramembranous oligomerization leading to a pore for cytochrome c efflux (Wei et al. 2000).
REACT_6160 (Reactome) tBID binds to inactive BAX in the cytosol (Eskes et al. 2000).
REACT_750 (Reactome) Once BCL2L11 (BIM) dissociates from the cytoskeleton, it translocates to the outer mitochondrial membrane where it associates with BCL2 (Puthalakath et al. 1999).
REACT_784 (Reactome) BCL2 binds tBID and inhibits BID-induced cytochrome C release and apoptosis (Yi et al. 2003).
SMAC XIAPArrowREACT_1035 (Reactome)
SMAC XIAPArrowREACT_1300 (Reactome)
SMAC XIAPArrowREACT_2102 (Reactome)
XIAP Caspase-3REACT_1090 (Reactome)
XIAP Caspase-7REACT_2091 (Reactome)
XIAP Caspase-9REACT_1312 (Reactome)
active caspase-3ArrowREACT_1300 (Reactome)
active caspase-3ArrowREACT_1460 (Reactome)
active caspase-7ArrowREACT_2102 (Reactome)
active caspase-7ArrowREACT_2165 (Reactome)
active caspase-8REACT_1320 (Reactome)
p-BCL2L11ArrowREACT_1888 (Reactome)
p-BMFArrowREACT_1981 (Reactome)
p-S15-TP53ArrowREACT_1555 (Reactome)
p-S15-TP53ArrowREACT_2201 (Reactome)
p-S99-BADArrowREACT_12565 (Reactome)
p-S99-BADREACT_1139 (Reactome)
tBID BCL-2REACT_1062 (Reactome)

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