KEGG   PATHWAY: pvp04210
Entry
pvp04210                    Pathway                                
Name
Apoptosis - Pteropus vampyrus (large flying fox)
Description
Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled by numerous interrelating processes. The 'extrinsic' pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. The 'intrinsic' pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. The central event in the 'intrinsic' pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. The third major pathway is initiated by the constituents of cytotoxic granules (e.g. Perforin and Granzyme B) that are released by CTLs (cytotoxic T-cells) and NK (natural killer) cells. Granzyme B, similarly to the caspases, cleaves its substrates after aspartic acid residues, suggesting that this protease has the ability to activate members of the caspase family directly. It is the balance between the pro-apoptotic and anti-apoptotic signals that eventually determines whether cells will undergo apoptosis, survive or proliferate. TNF family of ligands activates anti-apoptotic or cell-survival signals as well as apoptotic signals. NGF and Interleukin-3 promotes the survival, proliferation and differentiation of neurons or hematopoietic cells, respectively. Withdrawal of these growth factors leads to cell death, as described above.
Class
Cellular Processes; Cell growth and death
Pathway map
pvp04210  Apoptosis
pvp04210

Other DBs
GO: 0006915
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105305707  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
105296657  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B [KO:K04722]
105299797  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
105293104  FAS; tumor necrosis factor receptor superfamily member 6 isoform X5 [KO:K04390]
105307475  FADD; FAS-associated death domain protein [KO:K02373]
105305325  TNF; tumor necrosis factor [KO:K03156]
105295979  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
105305700  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
105298129  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
105298127  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105298128  CASP10; caspase-10 isoform X3 [KO:K04400] [EC:3.4.22.63]
105292998  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
105294710  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105291475  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
105297238  BID; BH3-interacting domain death agonist isoform X2 [KO:K04726]
105301762  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
111728746  bcl-2 homologous antagonist/killer-like [KO:K14021]
105301000  bcl-2 homologous antagonist/killer [KO:K14021]
105289190  DIABLO; diablo homolog, mitochondrial [KO:K10522]
105302118  SEPT4; septin-4 isoform X6 [KO:K16943]
105290726  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
105293163  cytochrome c [KO:K08738]
105288270  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
105294412  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105300124  PRF1; perforin-1 [KO:K07818]
105302752  granzyme B-like [KO:K01353] [EC:3.4.21.79]
105302756  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
105297234  TUBA8; tubulin alpha-8 chain [KO:K07374]
105297536  TUBA1B; tubulin alpha-1B chain isoform X1 [KO:K07374]
105297537  tubulin alpha-1B chain-like [KO:K07374]
105297584  tubulin alpha-1C chain-like [KO:K07374]
105291036  tubulin alpha-4A chain [KO:K07374]
105291037  tubulin alpha-1B chain-like [KO:K07374]
105303816  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
105301152  ACTG1; actin, cytoplasmic 2 [KO:K05692]
105294565  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
105294808  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
105296349  LMNA; lamin isoform X1 [KO:K12641]
105290906  LMNB1; lamin-B1 [KO:K07611]
105300422  LMNB2; lamin-B2 isoform X1 [KO:K07611]
105292609  PARP1; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
105308940  PARP2; poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
105302446  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
105295129  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
105294380  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
105299198  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
105294801  ENDOG; endonuclease G, mitochondrial isoform X1 [KO:K01173]
105308313  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
105297760  ERN1; LOW QUALITY PROTEIN: serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
105298613  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
105295171  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105294112  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105301042  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105297886  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
105292618  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
105297472  LOW QUALITY PROTEIN: caspase-12-like [KO:K04741] [EC:3.4.22.-]
105302307  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
105308244  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
105298070  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105307377  DDIT3; DNA damage-inducible transcript 3 protein isoform X1 [KO:K04452]
105291573  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
105294191  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
105299530  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
105311653  cathepsin D-like [KO:K01379] [EC:3.4.23.5]
105311654  uncharacterized protein LOC105311654 [KO:K01379] [EC:3.4.23.5]
105297949  CTSF; LOW QUALITY PROTEIN: cathepsin F [KO:K01373] [EC:3.4.22.41]
105301620  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
105303821  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
105306474  LOW QUALITY PROTEIN: cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
105306921  cathepsin L1-like isoform X1 [KO:K01365] [EC:3.4.22.15]
105308899  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
105292226  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
105303820  CTSS; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
105297919  CTSW; cathepsin W isoform X2 [KO:K08569] [EC:3.4.22.-]
105296094  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
105298277  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
105298278  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
105304241  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
105293400  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
105303970  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
105305503  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
105292717  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
105300991  DAXX; death domain-associated protein 6 [KO:K02308]
105296778  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
105292670  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
105289473  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
105288933  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105289628  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
105299978  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105297848  BAD; bcl2-associated agonist of cell death [KO:K02158]
105303436  JUN; transcription factor AP-1 [KO:K04448]
105299213  FOS; proto-oncogene c-Fos [KO:K04379]
105291226  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105303461  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
105304619  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105301022  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105302532  IKBKG; NF-kappa-B essential modulator [KO:K07210]
105303182  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105293029  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105297999  RELA; transcription factor p65 [KO:K04735]
105289627  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
105300252  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105300424  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105295887  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105292663  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
105297463  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
105305941  PIDD1; p53-induced death domain-containing protein 1 isoform X3 [KO:K10130]
105297315  BBC3; bcl-2-binding component 3 [KO:K10132]
105292725  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
105304116  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
105296475  NGF; beta-nerve growth factor isoform X2 [KO:K02582]
105296416  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
105293643  interleukin-3-like [KO:K04736]
105308004  interleukin-3 receptor subunit alpha-like [KO:K04737]
105288307  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105297140  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105303144  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105300159  RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C00319  Sphingosine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:26615431
  Authors
Savitskaya MA, Onishchenko GE
  Title
Mechanisms of Apoptosis.
  Journal
Biochemistry (Mosc) 80:1393-417 (2015)
DOI:10.1134/S0006297915110012
Reference
PMID:23803157
  Authors
Schleich K, Lavrik IN
  Title
Mathematical modeling of apoptosis.
  Journal
Cell Commun Signal 11:44 (2013)
DOI:10.1186/1478-811X-11-44
Reference
PMID:15654015
  Authors
Lavrik I, Golks A, Krammer PH
  Title
Death receptor signaling.
  Journal
J Cell Sci 118:265-7 (2005)
DOI:10.1242/jcs.01610
Reference
PMID:15725726
  Authors
Jin Z, El-Deiry WS
  Title
Overview of cell death signaling pathways.
  Journal
Cancer Biol Ther 4:139-63 (2005)
DOI:10.4161/cbt.4.2.1508
Reference
PMID:15322527
  Authors
Benn SC, Woolf CJ
  Title
Adult neuron survival strategies--slamming on the brakes.
  Journal
Nat Rev Neurosci 5:686-700 (2004)
DOI:10.1038/nrn1477
Reference
PMID:12838338
  Authors
Orrenius S, Zhivotovsky B, Nicotera P
  Title
Regulation of cell death: the calcium-apoptosis link.
  Journal
Nat Rev Mol Cell Biol 4:552-65 (2003)
DOI:10.1038/nrm1150
Reference
PMID:19148180
  Authors
Clarke P, Tyler KL
  Title
Apoptosis in animal models of virus-induced disease.
  Journal
Nat Rev Microbiol 7:144-55 (2009)
DOI:10.1038/nrmicro2071
Reference
PMID:22429822
  Authors
Wen X, Lin ZQ, Liu B, Wei YQ
  Title
Caspase-mediated programmed cell death pathways as potential therapeutic targets in cancer.
  Journal
Cell Prolif 45:217-24 (2012)
DOI:10.1111/j.1365-2184.2012.00814.x
Reference
PMID:25526085
  Authors
Shalini S, Dorstyn L, Dawar S, Kumar S
  Title
Old, new and emerging functions of caspases.
  Journal
Cell Death Differ 22:526-39 (2015)
DOI:10.1038/cdd.2014.216
Reference
PMID:15601572
  Authors
Philchenkov A
  Title
Caspases: potential targets for regulating cell death.
  Journal
J Cell Mol Med 8:432-44 (2004)
DOI:10.1111/j.1582-4934.2004.tb00468.x
Reference
PMID:9894605
  Authors
Stroh C, Schulze-Osthoff K
  Title
Death by a thousand cuts: an ever increasing list of caspase substrates.
  Journal
Cell Death Differ 5:997-1000 (1998)
DOI:10.1038/sj.cdd.4400451
Reference
PMID:23070002
  Authors
Safa AR
  Title
c-FLIP, a master anti-apoptotic regulator.
  Journal
Exp Oncol 34:176-84 (2012)
Reference
PMID:18304445
  Authors
Jeong SY, Seol DW
  Title
The role of mitochondria in apoptosis.
  Journal
BMB Rep 41:11-22 (2008)
DOI:10.5483/bmbrep.2008.41.1.011
Reference
PMID:20533903
  Authors
Parsons MJ, Green DR
  Title
Mitochondria in cell death.
  Journal
Essays Biochem 47:99-114 (2010)
DOI:10.1042/bse0470099
Reference
PMID:15719025
  Authors
Strasser A
  Title
The role of BH3-only proteins in the immune system.
  Journal
Nat Rev Immunol 5:189-200 (2005)
DOI:10.1038/nri1568
Reference
PMID:24278747
  Authors
Schonthal AH
  Title
Endoplasmic reticulum stress: its role in disease and novel prospects for therapy.
  Journal
Scientifica (Cairo) 2012:857516 (2012)
DOI:10.6064/2012/857516
Reference
PMID:21145844
  Authors
Malhi H, Kaufman RJ
  Title
Endoplasmic reticulum stress in liver disease.
  Journal
J Hepatol 54:795-809 (2011)
DOI:10.1016/j.jhep.2010.11.005
Reference
PMID:18023214
  Authors
Malhotra JD, Kaufman RJ
  Title
The endoplasmic reticulum and the unfolded protein response.
  Journal
Semin Cell Dev Biol 18:716-31 (2007)
DOI:10.1016/j.semcdb.2007.09.003
Reference
PMID:16397578
  Authors
Wu J, Kaufman RJ
  Title
From acute ER stress to physiological roles of the Unfolded Protein Response.
  Journal
Cell Death Differ 13:374-84 (2006)
DOI:10.1038/sj.cdd.4401840
Reference
PMID:21914490
  Authors
Repnik U, Stoka V, Turk V, Turk B
  Title
Lysosomes and lysosomal cathepsins in cell death.
  Journal
Biochim Biophys Acta 1824:22-33 (2012)
DOI:10.1016/j.bbapap.2011.08.016
Reference
PMID:22465226
  Authors
Cesen MH, Pegan K, Spes A, Turk B
  Title
Lysosomal pathways to cell death and their therapeutic applications.
  Journal
Exp Cell Res 318:1245-51 (2012)
DOI:10.1016/j.yexcr.2012.03.005
Reference
PMID:26231733
  Authors
Dashzeveg N, Yoshida K
  Title
Cell death decision by p53 via control of the mitochondrial membrane.
  Journal
Cancer Lett 367:108-12 (2015)
DOI:10.1016/j.canlet.2015.07.019
Reference
PMID:22075987
  Authors
Bouchier-Hayes L, Green DR
  Title
Caspase-2: the orphan caspase.
  Journal
Cell Death Differ 19:51-7 (2012)
DOI:10.1038/cdd.2011.157
Reference
PMID:18238895
  Authors
Baptiste-Okoh N, Barsotti AM, Prives C
  Title
A role for caspase 2 and PIDD in the process of p53-mediated apoptosis.
  Journal
Proc Natl Acad Sci U S A 105:1937-42 (2008)
DOI:10.1073/pnas.0711800105
Reference
PMID:12949498
  Authors
Aggarwal BB
  Title
Signalling pathways of the TNF superfamily: a double-edged sword.
  Journal
Nat Rev Immunol 3:745-56 (2003)
DOI:10.1038/nri1184
Reference
PMID:14737178
  Authors
Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA.
  Title
JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis.
  Journal
Leukemia 18:189-218 (2004)
DOI:10.1038/sj.leu.2403241
Reference
PMID:9916983
  Authors
Dragovich T, Rudin CM, Thompson CB
  Title
Signal transduction pathways that regulate cell survival and cell death.
  Journal
Oncogene 17:3207-13 (1998)
DOI:10.1038/sj.onc.1202587
Reference
PMID:11520933
  Authors
Sofroniew MV, Howe CL, Mobley WC
  Title
Nerve growth factor signaling, neuroprotection, and neural repair.
  Journal
Annu Rev Neurosci 24:1217-81 (2001)
DOI:10.1146/annurev.neuro.24.1.1217
Reference
PMID:24769728
  Authors
Kristiansen M, Ham J
  Title
Programmed cell death during neuronal development: the sympathetic neuron model.
  Journal
Cell Death Differ 21:1025-35 (2014)
DOI:10.1038/cdd.2014.47
Reference
PMID:18208375
  Authors
Logue SE, Martin SJ
  Title
Caspase activation cascades in apoptosis.
  Journal
Biochem Soc Trans 36:1-9 (2008)
DOI:10.1042/BST0360001
Reference
PMID:19770840
  Authors
Boivin WA, Cooper DM, Hiebert PR, Granville DJ
  Title
Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma.
  Journal
Lab Invest 89:1195-220 (2009)
DOI:10.1038/labinvest.2009.91
Reference
PMID:20075940
  Authors
Cullen SP, Brunet M, Martin SJ
  Title
Granzymes in cancer and immunity.
  Journal
Cell Death Differ 17:616-23 (2010)
DOI:10.1038/cdd.2009.206
Related
pathway
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
pvp04064  NF-kappa B signaling pathway
pvp04115  p53 signaling pathway
pvp04141  Protein processing in endoplasmic reticulum
pvp04151  PI3K-Akt signaling pathway
pvp04650  Natural killer cell mediated cytotoxicity
pvp04668  TNF signaling pathway
KO pathway
ko04210   
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