KEGG   PATHWAY: shr04210
Entry
shr04210                    Pathway                                
Name
Apoptosis - Sarcophilus harrisii (Tasmanian devil)
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
shr04210  Apoptosis
shr04210

Other DBs
GO: 0006915
Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100913229  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.-]
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100913262  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913330  [KO:K04741] [EC:3.4.22.-]
100913341  DAXX; death domain-associated protein 6 isoform X6 [KO:K02308]
100913383  [KO:K01365] [EC:3.4.22.15]
100913624  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100913697  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100913862  [KO:K04741] [EC:3.4.22.-]
100913913  [KO:K01353] [EC:3.4.21.79]
100914028  [KO:K16060]
100914125  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
100914177  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
100914243  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
100914278  [KO:K07374]
100915385  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
100915526  KRAS; GTPase KRas isoform X1 [KO:K07827]
100915548  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100916388  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
100916712  [KO:K05692]
100916731  BAK1; bcl-2 homologous antagonist/killer isoform X2 [KO:K14021]
100916996  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
100917184  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
100917254  SEPTIN4; septin-4 [KO:K16943]
100917396  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
100917439  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
100917440  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
100917568  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
100917619  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100917948  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
100917987  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100918124  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100918532  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X7 [KO:K04958]
100919027  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
100919051  ACTB; actin, cytoplasmic 1 [KO:K05692]
100919198  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
100919278  PRF1; perforin-1 [KO:K07818]
100919671  [KO:K08738]
100919761  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
100919776  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
100919788  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100919881  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
100920114  DFFA; LOW QUALITY PROTEIN: DNA fragmentation factor subunit alpha [KO:K02310]
100920178  LMNB2; lamin-B2 [KO:K07611]
100920439  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100920490  [KO:K07374]
100920513  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
100920562  [KO:K07374]
100920867  [KO:K01353] [EC:3.4.21.79]
100921025  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
100921270  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100921875  TNF; tumor necrosis factor [KO:K03156]
100921899  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
100922473  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
100922500  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100922649  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100922757  [KO:K02187] [EC:3.4.22.56]
100923083  LMNA; lamin [KO:K12641]
100923199  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
100923223  [KO:K07374]
100923807  [KO:K05692]
100923972  TUBA1C; tubulin alpha-1C chain [KO:K07374]
100923981  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
100924267  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100924435  FOS; proto-oncogene c-Fos [KO:K04379]
100924976  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100925167  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
100925410  DIABLO; diablo homolog, mitochondrial [KO:K10522]
100925440  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100925725  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
100925732  FADD; FAS-associated death domain protein [KO:K02373]
100926518  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
100926701  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
100926892  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100926902  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100927252  [KO:K07827]
100927306  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
100927375  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
100927376  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
100927621  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
100927679  PARP4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
100927801  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
100927927  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
100928240  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100928302  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100928401  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
100928480  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100928648  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
100928932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100928986  NRAS; GTPase NRas [KO:K07828]
100929168  [KO:K02833]
100929279  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X7 [KO:K06114]
100929426  [KO:K07827]
100929634  LMNB1; lamin-B1 [KO:K07611]
100929676  BID; BH3-interacting domain death agonist [KO:K04726]
100929775  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
100929811  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100930260  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
100930279  NGF; beta-nerve growth factor [KO:K02582]
100930815  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100931103  NOL3; nucleolar protein 3 isoform X2 [KO:K28177]
100931338  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
100931481  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
100931580  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100932053  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
100932099  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100932232  BCL2L11; LOW QUALITY PROTEIN: bcl-2-like protein 11 [KO:K16341]
100932473  RELA; transcription factor p65 [KO:K04735]
100932522  [KO:K07374]
100932636  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
100932786  [KO:K07374]
100933131  [KO:K16060]
100933419  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
100933548  [KO:K01365] [EC:3.4.22.15]
100933802  [KO:K01365] [EC:3.4.22.15]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100934619  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100934749  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
100934828  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
100935202  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
100935230  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100935398  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
105749071  [KO:K04722]
105749219  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
105749409  [KO:K02162]
105749979  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105749995  [KO:K04737]
105750042  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
105750684  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
105750812  [KO:K07374]
105750981  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
111718546  ENDOG; endonuclease G, mitochondrial [KO:K01173]
111721251  [KO:K08738]
116419913  HRAS; GTPase HRas [KO:K02833]
116420839  HRK; activator of apoptosis harakiri [KO:K02512]
116420883  [KO:K07374]
116421331  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
116421564  [KO:K01353] [EC:3.4.21.79]
116423037  BBC3; LOW QUALITY PROTEIN: bcl-2-binding component 3 [KO:K10132]
116423727  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116423739  JUN; transcription factor AP-1 [KO:K04448]
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
shr04010  MAPK signaling pathway
shr04020  Calcium signaling pathway
shr04064  NF-kappa B signaling pathway
shr04115  p53 signaling pathway
shr04141  Protein processing in endoplasmic reticulum
shr04151  PI3K-Akt signaling pathway
shr04650  Natural killer cell mediated cytotoxicity
shr04668  TNF signaling pathway
KO pathway
ko04210   

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