KEGG   PATHWAY: dro04210
Entry
dro04210                    Pathway                                
Name
Apoptosis - Desmodus rotundus (common vampire bat)
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
dro04210  Apoptosis
dro04210

Other DBs
GO: 0006915
Organism
Desmodus rotundus (common vampire bat) [GN:dro]
Gene
112296223  PARP4; poly [ADP-ribose] polymerase 4 isoform X1 [KO:K10798] [EC:2.4.2.-]
112296261  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112296279  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
112296379  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112296490  [KO:K01353] [EC:3.4.21.79]
112296519  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112296591  [KO:K01353] [EC:3.4.21.79]
112297049  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
112297079  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
112297551  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
112297566  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
112298319  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
112298609  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
112298712  ACTG1; actin, cytoplasmic 2 [KO:K05692]
112298801  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
112299050  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
112299099  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
112299448  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112299456  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
112300184  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
112300474  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
112300656  NOL3; nucleolar protein 3 [KO:K28177]
112300831  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
112301126  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112301616  IL3; interleukin-3 [KO:K04736]
112301743  [KO:K07374]
112301746  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112301806  [KO:K07374]
112302067  TNF; tumor necrosis factor isoform X1 [KO:K03156]
112302087  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
112302101  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
112302219  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112302733  CTSV; LOW QUALITY PROTEIN: cathepsin L2 [KO:K01365] [EC:3.4.22.15]
112302874  [KO:K01365] [EC:3.4.22.15]
112302993  [KO:K08731]
112303094  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
112304016  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
112304041  [KO:K07827]
112304196  BCL2L1; bcl-2-like protein 1 [KO:K04570]
112304801  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112305008  [KO:K04722]
112305224  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112305296  PRF1; perforin-1 [KO:K07818]
112305558  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112305948  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
112306083  [KO:K02162]
112306217  SPTAN1; spectrin alpha chain, non-erythrocytic 1 [KO:K06114]
112306355  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
112306414  ENDOG; endonuclease G, mitochondrial [KO:K01173]
112306448  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
112306476  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
112306749  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
112306993  [KO:K08738]
112307265  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112307358  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
112307528  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
112307654  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
112307667  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112307747  [KO:K07374]
112307787  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
112307926  [KO:K07374]
112308028  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
112308825  TP53; cellular tumor antigen p53 [KO:K04451]
112309280  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112309615  [KO:K10798] [EC:2.4.2.-]
112309625  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
112309686  [KO:K10798] [EC:2.4.2.-]
112310002  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
112310132  BAX; apoptosis regulator BAX [KO:K02159]
112310499  BID; BH3-interacting domain death agonist [KO:K04726]
112310530  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
112310632  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
112310731  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
112311304  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
112311345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112311412  FOS; proto-oncogene c-Fos [KO:K04379]
112311458  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112311601  TUBA8; tubulin alpha-8 chain [KO:K07374]
112311715  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
112312250  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
112312272  [KO:K04402]
112312320  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
112312400  LMNB2; lamin-B2 [KO:K07611]
112312410  [KO:K04402]
112312483  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112312833  BBC3; bcl-2-binding component 3 [KO:K10132]
112313317  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
112313500  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
112313687  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
112313707  NRAS; GTPase NRas [KO:K07828]
112313781  NGF; beta-nerve growth factor [KO:K02582]
112313792  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
112314270  [KO:K04741] [EC:3.4.22.-]
112314280  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
112314466  [KO:K02649]
112314642  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
112314999  LMNB1; lamin-B1 isoform X1 [KO:K07611]
112315668  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
112316040  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
112316166  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
112316288  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
112316363  SEPT4; septin-4 isoform X1 [KO:K16943]
112317099  HRAS; GTPase HRas isoform X1 [KO:K02833]
112317103  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
112317116  LMNA; lamin [KO:K12641]
112317121  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
112317131  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
112317202  RELA; transcription factor p65 [KO:K04735]
112317264  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
112317266  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
112317275  BAD; bcl2-associated agonist of cell death [KO:K02158]
112317320  FADD; FAS-associated death domain protein [KO:K02373]
112317424  [KO:K04722]
112317519  [KO:K16060]
112317544  [KO:K16060]
112317765  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
112317841  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112317867  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112318275  KRAS; LOW QUALITY PROTEIN: GTPase KRas [KO:K07827]
112318375  [KO:K07374]
112318382  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
112318638  [KO:K07374]
112318639  TUBA1B; tubulin alpha-1B chain [KO:K07374]
112318759  [KO:K03853] [EC:3.4.22.53]
112318849  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
112318919  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112319047  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
112319403  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
112319437  ACTB; actin, cytoplasmic 1 [KO:K05692]
112320130  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112320658  [KO:K08738]
112321016  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112321272  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
112321547  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
112321682  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112321814  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
112321955  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
112322009  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
112322221  [KO:K08738]
112322759  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
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
Reference
PMID:36652128
  Authors
Liu K, Lan D, Li C, Liu S, Dai X, Song T, Wang X, Kong Q, He Z, Tan J, Zhang J
  Title
A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.
  Journal
Apoptosis 28:313-325 (2023)
DOI:10.1007/s10495-022-01802-4
Related
pathway
dro04010  MAPK signaling pathway
dro04020  Calcium signaling pathway
dro04064  NF-kappa B signaling pathway
dro04115  p53 signaling pathway
dro04141  Protein processing in endoplasmic reticulum
dro04151  PI3K-Akt signaling pathway
dro04650  Natural killer cell mediated cytotoxicity
dro04668  TNF signaling pathway
KO pathway
ko04210   

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