KEGG   PATHWAY: ppam04210
Entry
ppam04210                   Pathway                                
Name
Apoptosis - Pteronotus mesoamericanus (Parnell's mustached 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
ppam04210  Apoptosis
ppam04210

Other DBs
GO: 0006915
Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129062360  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
129062398  LMNA; lamin isoform X1 [KO:K12641]
129062822  [KO:K08738]
129063024  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
129063946  NRAS; GTPase NRas [KO:K07828]
129063964  NGF; beta-nerve growth factor [KO:K02582]
129064112  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
129064157  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129064790  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
129064891  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
129065007  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
129065732  FOS; protein c-Fos [KO:K04379]
129065952  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
129066231  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129066330  [KO:K04736]
129066972  TNF; tumor necrosis factor [KO:K03156]
129066993  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
129067363  DAXX; death domain-associated protein 6 [KO:K02308]
129067386  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
129067800  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
129068452  [KO:K04722]
129068493  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
129068522  FADD; FAS-associated death domain protein [KO:K02373]
129068551  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
129068566  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
129068571  RELA; transcription factor p65 [KO:K04735]
129068584  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
129068612  BAD; bcl2-associated agonist of cell death [KO:K02158]
129069129  ACTB; actin, cytoplasmic 1 [KO:K05692]
129069407  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129069687  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
129069755  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
129069774  PRF1; perforin-1 [KO:K07818]
129069921  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
129070208  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
129070594  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
129070771  JUN; transcription factor Jun [KO:K04448]
129070790  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
129071324  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
129071395  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
129071418  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
129072028  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
129072137  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
129072290  TP53; cellular tumor antigen p53 [KO:K04451]
129072553  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
129072574  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
129072821  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
129072993  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
129073010  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
129073033  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129073113  HRAS; GTPase HRas isoform X1 [KO:K02833]
129073140  PIDD1; LOW QUALITY PROTEIN: p53-induced death domain-containing protein 1 [KO:K10130]
129073196  [KO:K07374]
129073352  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
129073366  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
129073796  PARP4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
129074073  [KO:K01353] [EC:3.4.21.79]
129074074  [KO:K01353] [EC:3.4.21.79]
129074378  IKBKG; NF-kappa-B essential modulator [KO:K07210]
129074590  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129074927  [KO:K04722]
129074969  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129075091  NOL3; nucleolar protein 3 [KO:K28177]
129075095  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
129075586  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
129075664  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
129075675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129075812  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
129076417  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
129076577  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129076641  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129076820  [KO:K01365] [EC:3.4.22.15]
129076822  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
129076823  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
129076831  [KO:K01371] [EC:3.4.22.38]
129077110  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
129077317  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
129077836  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129078069  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129078155  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129078478  CTSL; LOW QUALITY PROTEIN: procathepsin L [KO:K01365] [EC:3.4.22.15]
129078582  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
129078764  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129078902  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 isoform X1 [KO:K10131]
129079224  ENDOG; endonuclease G, mitochondrial [KO:K01173]
129079226  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
129079303  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
129079528  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
129079617  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
129079762  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
129080181  SEPTIN4; septin-4 isoform X1 [KO:K16943]
129080325  [KO:K07374]
129080327  [KO:K07374]
129080427  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
129080428  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
129080711  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
129080851  [KO:K07374]
129080992  TUBA8; tubulin alpha-8 chain [KO:K07374]
129081112  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
129081160  BID; BH3-interacting domain death agonist [KO:K04726]
129081375  LMNB2; LOW QUALITY PROTEIN: lamin-B2 [KO:K07611]
129081899  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
129082066  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129082206  [KO:K01365] [EC:3.4.22.15]
129082218  [KO:K08738]
129082291  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
129082301  [KO:K01365] [EC:3.4.22.15]
129082379  [KO:K01365] [EC:3.4.22.15]
129082775  BBC3; bcl-2-binding component 3 [KO:K10132]
129082924  BAX; apoptosis regulator BAX [KO:K02159]
129083088  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
129083099  BCL2A1; bcl-2-related protein A1 [KO:K02162]
129083450  [KO:K08738]
129083475  LMNB1; lamin-B1 [KO:K07611]
129083615  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
129084054  [KO:K19901]
129084433  [KO:K08738]
129084868  TUBA1C; tubulin alpha-1C chain [KO:K07374]
129084870  [KO:K07374]
129084873  [KO:K07374]
129084896  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
129084965  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
129084969  KRAS; GTPase KRas isoform X1 [KO:K07827]
129085322  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
129085375  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
129085376  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
129085416  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
129085546  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
129085559  EIF2AK3; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
129085864  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
129085986  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
129086012  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
129086067  [KO:K04741] [EC:3.4.22.-]
129086248  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129086316  [KO:K07374]
129086325  [KO:K07374]
129086451  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
129086550  ACTG1; actin, cytoplasmic 2 [KO:K05692]
129086565  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
129086785  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
129087253  DIABLO; diablo IAP-binding mitochondrial protein isoform X1 [KO:K10522]
129087312  HRK; activator of apoptosis harakiri [KO:K02512]
129087685  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
129087724  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.-]
129088291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129088423  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
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
ppam04010  MAPK signaling pathway
ppam04020  Calcium signaling pathway
ppam04064  NF-kappa B signaling pathway
ppam04115  p53 signaling pathway
ppam04141  Protein processing in endoplasmic reticulum
ppam04151  PI3K-Akt signaling pathway
ppam04650  Natural killer cell mediated cytotoxicity
ppam04668  TNF signaling pathway
KO pathway
ko04210   

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