KEGG   PATHWAY: fca04210
Entry
fca04210                    Pathway                                
Name
Apoptosis - Felis catus (domestic cat)
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
fca04210  Apoptosis
fca04210

Other DBs
GO: 0006915
Organism
Felis catus (domestic cat) [GN:fca]
Gene
100113473  PRF1; perforin-1 precursor [KO:K07818]
100127106  GZMB; granzyme B(G,H) [KO:K01353] [EC:3.4.21.79]
100135767  CASP12; inactive caspase-12 [KO:K04741] [EC:3.4.22.-]
100142680  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
100142683  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100142684  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100144390  CTSW; cathepsin W precursor [KO:K08569] [EC:3.4.22.-]
100144392  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100144609  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X2 [KO:K02374]
100144611  NGF; beta-nerve growth factor [KO:K02582]
100174789  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
100502578  BID; BH3-interacting domain death agonist [KO:K04726]
101080443  [KO:K01365] [EC:3.4.22.15]
101080748  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
101080975  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
101081387  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X3 [KO:K04368] [EC:2.7.12.2]
101081434  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070]
101081603  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
101081819  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
101081992  [KO:K07374]
101082042  LMNB2; lamin-B2 [KO:K07611]
101082519  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
101082639  [KO:K01365] [EC:3.4.22.15]
101082912  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
101083231  CAPN2; calpain-2 catalytic subunit isoform X2 [KO:K03853] [EC:3.4.22.53]
101083283  CTSS; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
101083444  [KO:K16060]
101083468  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101084148  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
101084297  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101084615  BCL2L11; bcl-2-like protein 11 isoform X6 [KO:K16341]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101084873  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
101085995  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
101086199  LMNA; lamin [KO:K12641]
101086480  BCL2A1; bcl-2-related protein A1 [KO:K02162]
101086509  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101086544  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101086605  [KO:K01365] [EC:3.4.22.15]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087620  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
101087663  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
101087871  FADD; FAS-associated death domain protein [KO:K02373]
101087880  [KO:K01365] [EC:3.4.22.15]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101087958  MAPK3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
101087971  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101087983  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
101087993  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101088041  NOL3; nucleolar protein 3 isoform X2 [KO:K28177]
101088122  [KO:K08738]
101088318  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
101088339  [KO:K08738]
101089265  DAXX; death domain-associated protein 6 [KO:K02308]
101089291  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
101089830  LMNB1; lamin-B1 [KO:K07611]
101090556  [KO:K07374]
101090594  [KO:K04725] [EC:2.3.2.27]
101090622  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101090686  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
101090944  PARP2; poly [ADP-ribose] polymerase 2 isoform X3 [KO:K28005]
101091160  DAB2IP; disabled homolog 2-interacting protein isoform X3 [KO:K19901]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101091455  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
101091636  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
101091892  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101092074  PARP4; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
101092127  DFFB; DNA fragmentation factor subunit beta isoform X2 [KO:K02311] [EC:3.-.-.-]
101092140  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
101092687  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101093286  [KO:K02649]
101093379  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
101093435  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101094274  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101094625  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
101095277  TUBA4A; tubulin alpha-4A chain isoform X2 [KO:K07374]
101095617  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101095973  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
101096047  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101096363  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
101096402  [KO:K07374]
101096522  SEPTIN4; septin-4 isoform X3 [KO:K16943]
101096604  RELA; transcription factor p65 [KO:K04735]
101096745  DFFA; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
101096902  TUBA1A; tubulin alpha-1A chain [KO:K07374]
101096916  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
101097261  JUN; transcription factor AP-1 [KO:K04448]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101097773  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X2 [KO:K03171]
101098213  [KO:K08738]
101098507  ACTB; actin, cytoplasmic 1 [KO:K05692]
101098780  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
101099215  [KO:K01353] [EC:3.4.21.79]
101099268  [KO:K07374]
101099835  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
101100038  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X2 [KO:K10798] [EC:2.4.2.-]
101100281  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101100546  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101100947  [KO:K08738]
101101230  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
101101663  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101101686  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X3 [KO:K06276] [EC:2.7.11.1]
102900397  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
105259631  [KO:K01365] [EC:3.4.22.15]
105261012  [KO:K04722]
105261394  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
109493221  HRK; activator of apoptosis harakiri [KO:K02512]
109503558  [KO:K08738]
111558033  BBC3; bcl-2-binding component 3 [KO:K10132]
111559122  [KO:K01365] [EC:3.4.22.15]
111559123  [KO:K01365] [EC:3.4.22.15]
111559124  [KO:K01365] [EC:3.4.22.15]
111560806  [KO:K04736]
493701  BCL2L1; bcl-2-like protein 1 [KO:K04570]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493835  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
493837  BAX; apoptosis regulator BAX [KO:K02159]
493847  TP53; cellular tumor antigen p53 [KO:K04451]
493881  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
493932  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
493934  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
493935  FOS; proto-oncogene c-Fos [KO:K04379]
493945  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
493957  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
493970  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
751103  HRAS; GTPase HRas isoform X1 [KO:K02833]
751104  KRAS; GTPase KRas isoform X2 [KO:K07827]
751105  NRAS; GTPase NRas [KO:K07828]
751112  PDP; procathepsin L isoform X1 [KO:K01365] [EC:3.4.22.15]
768257  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
768258  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
768259  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
768260  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
768261  PLA2G12A; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
768262  CASP7; caspase-7 isoform X2 [KO:K04397] [EC:3.4.22.60]
768264  ENDOG; endonuclease G, mitochondrial [KO:K01173]
768269  BAD; bcl2-associated agonist of cell death [KO:K02158]
768282  DIABLO; diablo homolog, mitochondrial [KO:K10522]
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
fca04010  MAPK signaling pathway
fca04020  Calcium signaling pathway
fca04064  NF-kappa B signaling pathway
fca04115  p53 signaling pathway
fca04141  Protein processing in endoplasmic reticulum
fca04151  PI3K-Akt signaling pathway
fca04650  Natural killer cell mediated cytotoxicity
fca04668  TNF signaling pathway
KO pathway
ko04210   

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