KEGG   PATHWAY: cfa04210
Entry
cfa04210                    Pathway                                
Name
Apoptosis - Canis lupus familiaris (dog)
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
cfa04210  Apoptosis
cfa04210

Other DBs
GO: 0006915
Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
100174780  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
100502558  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
100683675  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
100688321  [KO:K04722]
100688895  [KO:K01365] [EC:3.4.22.15]
100689004  [KO:K08738]
100855728  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100855995  [KO:K07374]
100856339  [KO:K02649]
100856405  TUBA1C; tubulin alpha-1C chain [KO:K07374]
102152063  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
102156614  CTSV; procathepsin L [KO:K01365] [EC:3.4.22.15]
106557476  [KO:K07374]
119866377  [KO:K07374]
403400  CTSS; cathepsin S precursor [KO:K01368] [EC:3.4.22.27]
403402  NGF; beta-nerve growth factor precursor [KO:K02582]
403416  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
403458  CTSC; dipeptidyl peptidase 1 precursor [KO:K01275] [EC:3.4.14.1]
403484  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X2 [KO:K06114]
403523  BAX; apoptosis regulator BAX [KO:K02159]
403537  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
403567  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
403580  ACTB; actin, cytoplasmic 1 [KO:K05692]
403618  BCL2L1; bcl-2-like protein 1 [KO:K04570]
403634  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X5 [KO:K03158]
403662  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X3 [KO:K02374]
403735  HRAS; GTPase HRas isoform 1 [KO:K02833]
403869  TP53; cellular tumor antigen p53 [KO:K04451]
403871  KRAS; GTPase KRas isoform X1 [KO:K07827]
403872  NRAS; GTPase NRas [KO:K07828]
403922  TNF; tumor necrosis factor [KO:K03156]
442859  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
442936  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
442964  AKT3; RAC-gamma serine/threonine-protein kinase isoform X8 [KO:K04456] [EC:2.7.11.1]
442968  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
442989  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
449021  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
474503  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
474652  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
474663  LMNB1; lamin-B1 isoform X2 [KO:K07611]
474873  DAXX; LOW QUALITY PROTEIN: death domain-associated protein 6 isoform X7 [KO:K02308]
475258  CYCS; cytochrome c [KO:K08738]
475392  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
475756  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X2 [KO:K08860] [EC:2.7.11.1]
475782  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
475923  ACTG1; actin, cytoplasmic 2 [KO:K05692]
476010  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
476215  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
476548  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
477085  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
477348  PARP4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
477463  DIABLO; diablo homolog, mitochondrial [KO:K10522]
477570  [KO:K07374]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
477746  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
477796  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
478347  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
478464  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
478918  TUBA4A; tubulin alpha-4A chain isoform X2 [KO:K07374]
479065  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
479450  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
479458  CASP12; caspase-12 [KO:K04741] [EC:3.4.22.-]
479464  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
479875  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X3 [KO:K06276] [EC:2.7.11.1]
480118  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
480124  LMNA; lamin [KO:K12641]
480291  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
480361  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
480571  SEPTIN4; septin-4 isoform X30 [KO:K16943]
480673  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
481048  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
481276  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
481497  IL3; interleukin-3 precursor [KO:K04736]
481744  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
481746  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
482620  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
482665  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
482737  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
482839  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
483649  PIDD1; p53-induced death domain-containing protein 1 isoform X4 [KO:K10130]
483662  CTSD; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
483725  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
483729  RELA; transcription factor p65 isoform X2 [KO:K04735]
483745  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
483763  BAD; bcl2-associated agonist of cell death [KO:K02158]
484140  CTSL3; procathepsin L [KO:K01365] [EC:3.4.22.15]
484198  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
484648  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
484745  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.-]
485069  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
485070  LMNB2; lamin-B2 isoform X3 [KO:K07611]
486077  CTSB; cathepsin B isoform X2 [KO:K01363] [EC:3.4.22.1]
486469  FAS; tumor necrosis factor receptor superfamily member 6 isoform X2 [KO:K04390]
486628  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
486762  TUBA8; tubulin alpha-8 chain isoform X12 [KO:K07374]
486896  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
487148  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
487235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
487432  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
487449  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
487899  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
488084  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
488471  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
488472  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
488473  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
488770  BCL2A1; bcl-2-related protein A1 [KO:K02162]
489030  PRF1; perforin-1 precursor [KO:K07818]
489433  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
489623  DFFB; DNA fragmentation factor subunit beta isoform X2 [KO:K02311] [EC:3.-.-.-]
489644  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
490385  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
490404  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
490630  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
490792  FOS; proto-oncogene c-Fos [KO:K04379]
490878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
490926  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
491356  DAB2IP; disabled homolog 2-interacting protein isoform X4 [KO:K19901]
607439  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
608051  [KO:K07374]
608843  CTSK; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
608916  ENDOG; endonuclease G, mitochondrial [KO:K01173]
609293  IL3RA; interleukin-3 receptor subunit alpha isoform X16 [KO:K04737]
609429  JUN; transcription factor AP-1 [KO:K04448]
609956  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
610636  [KO:K07374]
610766  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X6 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
611262  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X2 [KO:K03171]
611694  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
611939  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
611983  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
612153  BBC3; bcl-2-binding component 3 [KO:K10132]
612867  BCL2L11; bcl-2-like protein 11 isoform X4 [KO:K16341]
612984  HRK; activator of apoptosis harakiri [KO:K02512]
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
cfa04010  MAPK signaling pathway
cfa04020  Calcium signaling pathway
cfa04064  NF-kappa B signaling pathway
cfa04115  p53 signaling pathway
cfa04141  Protein processing in endoplasmic reticulum
cfa04151  PI3K-Akt signaling pathway
cfa04650  Natural killer cell mediated cytotoxicity
cfa04668  TNF signaling pathway
KO pathway
ko04210   

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