KEGG   PATHWAY: phas04210
Entry
phas04210                   Pathway                                
Name
Apoptosis - Phyllostomus hastatus (greater spear-nosed 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
phas04210  Apoptosis
phas04210

Other DBs
GO: 0006915
Organism
Phyllostomus hastatus (greater spear-nosed bat) [GN:phas]
Gene
123804387  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
123804406  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
123804409  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
123804414  NRAS; GTPase NRas [KO:K07828]
123804554  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
123804625  NGF; beta-nerve growth factor [KO:K02582]
123804648  LMNA; lamin [KO:K12641]
123804735  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
123805465  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
123805489  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
123805588  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
123806080  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
123806103  NOL3; nucleolar protein 3 [KO:K28177]
123806560  [KO:K07374]
123806569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123806781  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
123806785  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
123806817  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
123806902  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123807097  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
123807193  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123807317  HRAS; GTPase HRas isoform X1 [KO:K02833]
123807330  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
123807349  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
123807416  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
123807437  ACTB; actin, cytoplasmic 1 [KO:K05692]
123807522  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
123808110  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
123808178  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
123808226  FOS; proto-oncogene c-Fos [KO:K04379]
123808343  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
123808608  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123809443  TP53; cellular tumor antigen p53 [KO:K04451]
123809673  BCL2A1; bcl-2-related protein A1 [KO:K02162]
123809802  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
123810433  TNF; tumor necrosis factor isoform X1 [KO:K03156]
123810612  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
123810711  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
123811483  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
123811546  [KO:K08738]
123811721  [KO:K08738]
123812072  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
123812354  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
123812406  KRAS; GTPase KRas isoform X1 [KO:K07827]
123812775  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
123812863  [KO:K07374]
123812864  TUBA1C; tubulin alpha-1C chain [KO:K07374]
123813640  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123813828  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
123813874  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
123814022  LMNB2; lamin-B2 [KO:K07611]
123814149  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
123814364  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123814773  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
123814855  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
123815560  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
123815944  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
123816126  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123816219  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
123816228  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
123816301  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
123816474  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
123816481  DAXX; death domain-associated protein 6 [KO:K02308]
123816756  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
123816905  ACTG1; actin, cytoplasmic 2 [KO:K05692]
123816997  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
123817083  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
123817423  [KO:K16943]
123818096  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
123818154  LMNB1; lamin-B1 isoform X1 [KO:K07611]
123818449  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
123818526  [KO:K04741] [EC:3.4.22.-]
123818736  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
123818775  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
123819053  [KO:K04726]
123819465  [KO:K01365] [EC:3.4.22.15]
123819480  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
123819672  [KO:K19901]
123819750  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
123820403  HRK; activator of apoptosis harakiri [KO:K02512]
123820443  [KO:K01353] [EC:3.4.21.79]
123820457  [KO:K01353] [EC:3.4.21.79]
123820769  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
123820887  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123820944  PRF1; perforin-1 [KO:K07818]
123821582  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
123821729  DIABLO; diablo homolog, mitochondrial [KO:K10522]
123822662  PARP4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
123822762  TUBA3C; LOW QUALITY PROTEIN: tubulin alpha-3C chain [KO:K07374]
123823020  BBC3; bcl-2-binding component 3 [KO:K10132]
123823081  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
123823443  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
123823557  ENDOG; endonuclease G, mitochondrial [KO:K01173]
123823598  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
123823743  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123824432  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
123824433  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
123824482  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
123824527  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123825207  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
123825523  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123826047  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
123826163  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
123826264  [KO:K08738]
123826376  [KO:K08738]
123826750  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123826954  [KO:K08731]
123827114  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
123827723  [KO:K04725] [EC:2.3.2.27]
123827786  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
123828105  [KO:K07374]
123828291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123828317  [KO:K04722]
123828668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
123828762  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
123829139  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
123829336  BAD; bcl2-associated agonist of cell death [KO:K02158]
123829338  FADD; FAS-associated death domain protein [KO:K02373]
123829347  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
123829456  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
123829518  RELA; transcription factor p65 [KO:K04735]
123829587  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
123830027  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
123830279  BAX; apoptosis regulator BAX [KO:K02159]
123830457  [KO:K10798] [EC:2.4.2.-]
123830458  [KO:K10798] [EC:2.4.2.-]
123830469  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123830565  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123831001  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
123831161  TUBAL3; tubulin alpha chain-like 3 isoform X1 [KO:K07374]
123831409  JUN; transcription factor AP-1 [KO:K04448]
123831687  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
123831922  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123832238  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
123832288  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
123832297  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123832298  [KO:K02649]
123832759  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
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
phas04010  MAPK signaling pathway
phas04020  Calcium signaling pathway
phas04064  NF-kappa B signaling pathway
phas04115  p53 signaling pathway
phas04141  Protein processing in endoplasmic reticulum
phas04151  PI3K-Akt signaling pathway
phas04650  Natural killer cell mediated cytotoxicity
phas04668  TNF signaling pathway
KO pathway
ko04210   

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