KEGG   PATHWAY: csab04210
Entry
csab04210                   Pathway                                
Name
Apoptosis - Chlorocebus sabaeus (green monkey)
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
csab04210  Apoptosis
csab04210

Other DBs
GO: 0006915
Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103215020  [KO:K05692]
103215319  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
103215469  TNFRSF10B; TNF receptor superfamily member 10b [KO:K04722]
103215472  TNFRSF10A; TNF receptor superfamily member 10a [KO:K04722]
103215686  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103215844  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103216048  PRF1; perforin 1 [KO:K07818]
103216224  FAS; Fas cell surface death receptor [KO:K04390]
103216382  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
103216537  CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
103216844  TUBA3E; tubulin alpha 3e [KO:K07374]
103217237  [KO:K05692]
103217632  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
103217635  CASP10; caspase 10 [KO:K04400] [EC:3.4.22.63]
103217637  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
103217904  TUBA4A; tubulin alpha 4a [KO:K07374]
103218446  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
103218763  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103218776  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103218899  DAB2IP; DAB2 interacting protein [KO:K19901]
103218917  TRAF1; TNF receptor associated factor 1 [KO:K03172]
103219323  [KO:K05692]
103219556  [KO:K08738]
103219700  CTSL; cathepsin L [KO:K01365] [EC:3.4.22.15]
103219731  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
103219808  CTSV; cathepsin V [KO:K01375] [EC:3.4.22.43]
103220019  HTRA2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
103221212  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103221246  TNFSF10; tumor necrosis factor superfamily member 10 [KO:K04721]
103221651  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
103221654  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103221662  DAXX; death domain associated protein [KO:K02308]
103222283  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
103222435  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
103222594  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103222876  BID; BH3 interacting domain death agonist [KO:K04726]
103222884  TUBA8; tubulin alpha 8 [KO:K07374]
103222941  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103223258  CSF2RB; colony stimulating factor 2 receptor beta common subunit [KO:K04738]
103223345  ATF4; activating transcription factor 4 [KO:K04374]
103223823  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
103223838  LMNA; lamin A/C [KO:K12641]
103224160  NGF; nerve growth factor [KO:K02582]
103224167  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103224652  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
103224726  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
103224843  [KO:K08738]
103224900  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103225550  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
103225626  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
103225637  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103225665  [KO:K08738]
103225722  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
103225782  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
103227364  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103227412  CASP2; caspase 2 [KO:K02186] [EC:3.4.22.55]
103227705  PARP3; poly(ADP-ribose) polymerase family member 3 [KO:K10798] [EC:2.4.2.-]
103227941  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103228018  [KO:K08738]
103228031  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103228744  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
103228823  NFKBIA; NFKB inhibitor alpha [KO:K04734]
103229205  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
103229352  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103229784  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103229992  PARP1; poly(ADP-ribose) polymerase 1 [KO:K24070]
103230023  CAPN2; calpain 2 [KO:K03853] [EC:3.4.22.53]
103230332  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
103230532  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103230577  FASLG; Fas ligand [KO:K04389]
103230823  [KO:K05692]
103230869  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103231336  PARP2; poly(ADP-ribose) polymerase 2 [KO:K28005]
103232547  AIFM1; apoptosis inducing factor mitochondria associated 1 [KO:K04727] [EC:1.-.-.-]
103232832  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
103233291  TRADD; TNFRSF1A associated via death domain [KO:K03171]
103233293  BAD; BCL2 associated agonist of cell death [KO:K02158]
103233295  NOL3; nucleolar protein 3 [KO:K28177]
103233631  LMNB2; lamin B2 [KO:K07611]
103233650  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
103233717  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103233828  PIDD1; p53-induced death domain protein 1 [KO:K10130]
103234391  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103234702  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103234932  BBC3; BCL2 binding component 3 [KO:K10132]
103235004  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
103235918  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103235922  PTPN13; protein tyrosine phosphatase, non-receptor type 13 [KO:K02374]
103236047  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
103236104  CASP6; caspase 6 [KO:K04396] [EC:3.4.22.59]
103236433  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
103236614  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
103236841  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
103237818  TUBAL3; tubulin alpha like 3 [KO:K07374]
103238260  TUBA1B; tubulin alpha 1b [KO:K07374]
103238261  TUBA1A; tubulin alpha 1a [KO:K07374]
103238262  [KO:K07374]
103238566  DDIT3; DNA damage inducible transcript 3 [KO:K04452]
103238923  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
103239209  HRK; harakiri, BCL2 interacting protein [KO:K02512]
103239302  DIABLO; diablo IAP-binding mitochondrial protein [KO:K10522]
103239600  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
103239785  ENDOG; endonuclease G [KO:K01173]
103239794  SPTAN1; spectrin alpha, non-erythrocytic 1 [KO:K06114]
103239827  [KO:K08738]
103240310  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
103240948  [KO:K05692]
103240990  [KO:K08738]
103241244  BCL2L11; BCL2 like 11 [KO:K16341]
103241350  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
103241599  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103242323  TP53; tumor protein p53 [KO:K04451]
103242841  SEPT4; septin 4 [KO:K16943]
103243204  ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
103243289  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
103243445  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
103243654  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
103243719  ACTG1; actin gamma 1 [KO:K05692]
103244166  BCL2; BCL2, apoptosis regulator [KO:K02161]
103244190  [KO:K08738]
103244455  LMNB1; lamin B1 [KO:K07611]
103244501  IL3; interleukin 3 [KO:K04736]
103245120  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103245226  BCL2A1; BCL2 related protein A1 [KO:K02162]
103245241  CTSH; cathepsin H [KO:K01366] [EC:3.4.22.16]
103245451  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103245758  FADD; Fas associated via death domain [KO:K02373]
103246363  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103246953  ACTB; actin beta [KO:K05692]
103247197  MCL1; BCL2 family apoptosis regulator [KO:K02539]
103247206  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
103247207  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
103247375  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
103247515  IL3RA; interleukin 3 receptor subunit alpha [KO:K04737]
103247598  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
103247618  [KO:K01365] [EC:3.4.22.15]
103247857  [KO:K07374]
103248011  BCL2L1; BCL2 like 1 [KO:K04570]
103248190  CTSC; cathepsin C [KO:K01275] [EC:3.4.14.1]
103248332  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
103248333  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
103248368  [KO:K04741] [EC:3.4.22.-]
103248401  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
103248810  TP53AIP1; tumor protein p53 regulated apoptosis inducing protein 1 [KO:K13773]
103249024  PARP4; poly(ADP-ribose) polymerase family member 4 [KO:K10798] [EC:2.4.2.-]
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
csab04010  MAPK signaling pathway
csab04020  Calcium signaling pathway
csab04064  NF-kappa B signaling pathway
csab04115  p53 signaling pathway
csab04141  Protein processing in endoplasmic reticulum
csab04151  PI3K-Akt signaling pathway
csab04650  Natural killer cell mediated cytotoxicity
csab04668  TNF signaling pathway
KO pathway
ko04210   

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