Intrinsic Pathway for Apoptosis (Homo sapiens)

From WikiPathways

Revision as of 10:02, 6 October 2011 by MartijnVanIersel (Talk | contribs)
Jump to: navigation, search
1-3127271661016, 21, 2224, 251315430-3227, 2814, 16-1911, 14, 16-18824, 254261127149291332, 332330-3220152130mitochondrial outer membranecytosolmitochondrial inner membraneNOXA proteinCytochrome cADPNOXA proteinApoptosis regulator Bcl-XBcl-2 proteinSMAC:XIAP:Caspase-7Cytochrome cAKT1Bcl-XL interacting BH3-only proteinsactive caspase-7Cytochrome C:Apaf-1:ATP:Procaspase-9SMACBcl-2 interacting BH-3 only proteinsActivated BAK proteinNMT 1tBIDBcl2:BH3-only protein complexADPApoptosomeActivated BAX inserted into mitochondrial membrane143B:phospo-BAD complexCaspase-3 precursorCaspase-9 precursorSmac protein, mitochondrial precursorPUMA proteinSMAC:XIAP:Caspase-3PUMA protein14-3-3 protein beta/alphaBMFBIDSMAC:XIAP:Caspase-9BMF sequestered to dynein (DLC2)Phospho-BADBMFActive oligomeric BAKMitogen-activated protein kinase 8BAD:BCL-2tBID bound to inactive BAXCaspase-7 precursorBAD proteinBIM sequestered to dynein (DLC1)active caspase-3Granzyme BCaspase-8 dimerATPATPActivated BAXXIAP:Caspase-9XIAP:Caspase-7Inactive BAK proteinSMAC:XIAPtBID bound to inactive BAKtBID-p15tBID:BCL-2Apaf-1Apaf-1:Cytochrome CBIMCleaved Caspase-9XIAP:Caspase-3ATPCalcineurin B complextBIDBcl-XL:BH3-only protein complexActivated BAXphospho-dynein(DLC1) on microtubulesBIMDP-1:E2F1 complexInactive Bax alpha proteinBAD proteinADPphospho-dynein(DLC2) on microtubules544


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.</div>

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  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

View all...
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

View all...
NameTypeDatabase referenceComment
14-3-3 protein

beta/alpha

ProteinP31946 (UniProt)
143B:phospo-BAD

complex

ComplexREACT_5737 (Reactome)
ADP Metabolite16761 (ChEBI)
AKT1 ProteinP31749 (UniProt)
ATP Metabolite15422 (ChEBI)
Activated BAK

protein

ProteinQ16611 (UniProt)
Activated BAX ProteinQ07812 (UniProt)
Activated BAX ComplexREACT_2560 (Reactome)
Activated BAX

inserted into mitochondrial membrane

ProteinQ07812 (UniProt)
Active oligomeric

BAK

ComplexREACT_4956 (Reactome)
Apaf-1 ProteinO14727 (UniProt)
Apaf-1:Cytochrome

C

ComplexREACT_4880 (Reactome)
Apoptosis regulator

Bcl-X

ProteinQ07817 (UniProt)
Apoptosome ComplexREACT_3569 (Reactome)
BAD

protein

ProteinQ92934 (UniProt)
BAD:BCL-2 ComplexREACT_3232 (Reactome)
BID ProteinP55957 (UniProt)
BIM ProteinO43521-1 (UniProt)
BIM sequestered

to dynein (DLC1)

ComplexREACT_3567 (Reactome)
BMF ProteinQ96LC9 (UniProt)
BMF sequestered

to dynein (DLC2)

ComplexREACT_3065 (Reactome)
Bcl-2 interacting BH-

3 only proteins

ProteinREACT_21617 (Reactome)
Bcl-2 protein ProteinP10415 (UniProt)
Bcl-XL interacting

BH3-only proteins

ProteinREACT_21650 (Reactome)
Bcl-XL:BH3-only

protein complex

ComplexREACT_21559 (Reactome)
Bcl2:BH3-only

protein complex

ComplexREACT_21874 (Reactome)
Calcineurin B

complex

ComplexREACT_4613 (Reactome)
Caspase-3

precursor

ProteinP42574 (UniProt)
Caspase-7

precursor

ProteinP55210 (UniProt)
Caspase-8 dimer ComplexREACT_4185 (Reactome)
Caspase-9

precursor

ProteinP55211 (UniProt)
Cleaved

Caspase-9

ComplexREACT_5782 (Reactome)
Cytochrome C:Apaf-

1:ATP:Procaspase-9

ComplexREACT_5647 (Reactome)
Cytochrome c ProteinP99999 (UniProt)
DP-1:E2F1

complex

ComplexREACT_5400 (Reactome)
Granzyme B ProteinP10144 (UniProt)
Inactive BAK

protein

ProteinQ16611 (UniProt)
Inactive Bax alpha

protein

ProteinQ07812 (UniProt)
Mitogen-activated

protein kinase 8

ProteinP45983 (UniProt)
NMT 1 ProteinP30419 (UniProt)
NOXA

protein

ProteinQ13794 (UniProt)
PUMA

protein

ProteinQ9BXH1 (UniProt)
Phospho-BAD ProteinQ92934 (UniProt)
SMAC ProteinQ9NR28 (UniProt)
SMAC:XIAP ComplexREACT_5204 (Reactome)
SMAC:XIAP:

Caspase-3

ComplexREACT_5281 (Reactome)
SMAC:XIAP:

Caspase-7

ComplexREACT_3355 (Reactome)
SMAC:XIAP:

Caspase-9

ComplexREACT_4472 (Reactome)
Smac protein,

mitochondrial precursor

ProteinQ9NR28 (UniProt)
XIAP:Caspase-3 ComplexREACT_2704 (Reactome)
XIAP:Caspase-7 ComplexREACT_2853 (Reactome)
XIAP:Caspase-9 ComplexREACT_4334 (Reactome)
active caspase-3 ComplexREACT_2467 (Reactome)
active caspase-7 ComplexREACT_3366 (Reactome)
phospho-dynein

(DLC1) on microtubules

ComplexREACT_2522 (Reactome)
phospho-dynein

(DLC2) on microtubules

ComplexREACT_5554 (Reactome)
tBID ProteinP55957 (UniProt)
tBID bound to inactive

BAK

ComplexREACT_6608 (Reactome)
tBID bound to inactive

BAX

ComplexREACT_6691 (Reactome)
tBID-p15 ProteinP55957 (UniProt)
tBID:BCL-

2

ComplexREACT_5048 (Reactome)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1841"
Personal tools