KEGG   PATHWAY: ssc04210
Entry
ssc04210                    Pathway                                
Name
Apoptosis - Sus scrofa (pig)
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
ssc04210  Apoptosis
ssc04210

Other DBs
GO: 0006915
Organism
Sus scrofa (pig) [GN:ssc]
Gene
406191  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
100624226  tumor necrosis factor receptor superfamily member 10B-like isoform X1 [KO:K04722]
100737977  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
396726  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
396826  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
595129  FADD; FAS-associated death domain protein [KO:K02373]
397086  TNF; tumor necrosis factor [KO:K03156]
397020  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
100620340  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
414381  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
595105  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100154896  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
100517293  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
397244  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100156777  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
594852  BID; BH3-interacting domain death agonist [KO:K04726]
396633  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
397543  BAK1; bcl-2 homologous antagonist/killer isoform X2 [KO:K14021]
100155744  DIABLO; diablo homolog, mitochondrial [KO:K10522]
100515575  SEPT4; septin-4 isoform X1 [KO:K16943]
100512831  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
100170131  CYCS; cytochrome c [KO:K08738]
100522842  cytochrome c [KO:K08738]
100519295  cytochrome c-like [KO:K08738]
100621347  cytochrome c-like [KO:K08738]
100513283  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
100518913  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
396595  PRF1; perforin-1 [KO:K07818]
100233184  GZMB; granzyme B precursor [KO:K01353] [EC:3.4.21.79]
100739080  LOW QUALITY PROTEIN: mast cell protease 3 [KO:K01353] [EC:3.4.21.79]
733594  TUBA1B; tubulin alpha-1B chain [KO:K07374]
100151951  TUBA4A; tubulin alpha-4A chain [KO:K07374]
100155138  tubulin alpha-3 chain isoform X2 [KO:K07374]
100158003  LOW QUALITY PROTEIN: tubulin alpha-1D chain [KO:K07374]
100127131  tubulin alpha-1C chain isoform X2 [KO:K07374]
100518253  TUBA8; tubulin alpha-8 chain [KO:K07374]
100510930  tubulin alpha-3 chain isoform X2 [KO:K07374]
100135051  TUBA1A; tubulin alpha-1A chain [KO:K07374]
100623355  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
397648  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
397653  ACTG1; actin, cytoplasmic 2 [KO:K05692]
414396  ACTB; actin, cytoplasmic 1 [KO:K05692]
100049693  SPTAN1; LOW QUALITY PROTEIN: spectrin alpha chain, non-erythrocytic 1 [KO:K06114]
100126859  LMNA; prelamin-A/C [KO:K12641]
100513342  LMNB1; lamin-B1 [KO:K07611]
100620983  LMNB2; lamin-B2 [KO:K07611]
100621034  PARP1; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
100518917  PARP2; poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
100620838  PARP3; poly [ADP-ribose] polymerase 3 isoform X1 [KO:K10798] [EC:2.4.2.30]
100738726  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
100523126  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
100513357  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
100514888  ENDOG; endonuclease G, mitochondrial [KO:K01173]
100524062  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
100510978  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
100513840  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
397454  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100517279  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100155015  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
397027  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
397393  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100513348  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
100155472  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
100144302  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100240743  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
100037961  CTSB; cathepsin B precursor [KO:K01363] [EC:3.4.22.1]
100522387  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
494568  CTSD; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
100520004  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
396969  CTSH; pro-cathepsin H precursor [KO:K01366] [EC:3.4.22.16]
397569  CTSK; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
396926  CTSV; cathepsin L1 precursor [KO:K01365] [EC:3.4.22.15]
100515919  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
100737564  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
100153090  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
100525853  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
100141405  CTSZ; cathepsin Z precursor [KO:K08568] [EC:3.4.18.1]
100622859  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
100622590  BIRC3; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 3 [KO:K16060]
100037300  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
397266  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
396632  BCL2L11; bcl-2-like protein 11 isoform 2 [KO:K16341]
397536  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100049703  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100524813  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
100524751  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
100628179  DAB2IP; LOW QUALITY PROTEIN: disabled homolog 2-interacting protein [KO:K19901]
100622769  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
396610  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100521736  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
396609  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
100521065  BAD; LOW QUALITY PROTEIN: bcl2-associated agonist of cell death [KO:K02158]
396913  JUN; transcription factor AP-1 [KO:K04448]
100144486  FOS; proto-oncogene c-Fos [KO:K04379]
397276  TP53; cellular tumor antigen p53 [KO:K04451]
100155596  HRK; activator of apoptosis harakiri [KO:K02512]
100520402  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100135662  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
100101471  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100127355  IKBKG; NF-kappa-B essential modulator [KO:K07210]
406188  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
751869  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
100135665  RELA; transcription factor p65 [KO:K04735]
100521910  PTPN13; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
100152997  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
733669  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100621090  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100627029  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
100156860  BCL2A1; bcl-2-related protein A1 [KO:K02162]
100101922  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
102167527  PIDD1; p53-induced death domain-containing protein 1 isoform X3 [KO:K10130]
100517403  BBC3; bcl-2-binding component 3 isoform X3 [KO:K10132]
397278  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
100521118  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
100738968  NGF; beta-nerve growth factor [KO:K02582]
100154471  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
100153254  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
100518131  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100621789  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100622559  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100511937  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100739510  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100623707  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100192445  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100126861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100513811  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100127478  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110259208  HRAS; GTPase HRas isoform X1 [KO:K02833]
100518251  KRAS; GTPase KRas isoform X2 [KO:K07827]
100739349  NRAS; GTPase NRas precursor [KO:K07828]
100737448  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100233191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100525505  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100153927  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
445013  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
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
Related
pathway
ssc04010  MAPK signaling pathway
ssc04020  Calcium signaling pathway
ssc04064  NF-kappa B signaling pathway
ssc04115  p53 signaling pathway
ssc04141  Protein processing in endoplasmic reticulum
ssc04151  PI3K-Akt signaling pathway
ssc04650  Natural killer cell mediated cytotoxicity
ssc04668  TNF signaling pathway
KO pathway
ko04210   
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