KEGG   PATHWAY: pcad04210
Entry
pcad04210                   Pathway                                
Name
Apoptosis - Physeter catodon (sperm whale)
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
pcad04210  Apoptosis
pcad04210

Other DBs
GO: 0006915
Organism
Physeter catodon (sperm whale) [GN:pcad]
Gene
102992913  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
102979472  tumor necrosis factor receptor superfamily member 10B [KO:K04722]
102980036  tumor necrosis factor receptor superfamily member 10B isoform X1 [KO:K04722]
102979864  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102985097  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
102973514  FAS-associated death domain protein isoform X1 [KO:K02373]
112067437  FAS-associated death domain protein isoform X1 [KO:K02373]
102983069  TNF; tumor necrosis factor [KO:K03156]
102980613  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
102986061  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
102981647  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
102988082  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
102989304  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
102979663  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
102980899  LOW QUALITY PROTEIN: caspase-6-like [KO:K04396] [EC:3.4.22.59]
102977692  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
102974187  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
102991092  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102996565  DIABLO; diablo IAP-binding mitochondrial protein isoform X1 [KO:K10522]
102980430  septin-4 isoform X5 [KO:K16943]
102995172  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
102980282  cytochrome c-like [KO:K08738]
112066660  cytochrome c [KO:K08738]
112063874  cytochrome c-like [KO:K08738]
102978471  cytochrome c-like [KO:K08738]
102986675  cytochrome c-like [KO:K08738]
102977457  cytochrome c 2 [KO:K08738]
102978194  cytochrome c-like [KO:K08738]
102994125  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
102989458  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
102992503  PRF1; perforin-1 [KO:K07818]
102996600  granzyme B isoform X1 [KO:K01353] [EC:3.4.21.79]
102996887  LOW QUALITY PROTEIN: mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
102979938  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
102982837  tubulin alpha-4A chain [KO:K07374]
102990956  tubulin alpha-1D chain-like [KO:K07374]
102987728  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
102980636  tubulin alpha-1C chain [KO:K07374]
102990900  tubulin alpha-1B chain [KO:K07374]
112064711  tubulin alpha-1B chain [KO:K07374]
112067146  tubulin alpha-1B chain-like [KO:K07374]
102992310  tubulin alpha-3 chain [KO:K07374]
112061831  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
102993677  LOW QUALITY PROTEIN: induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
102988048  ACTG1; actin, cytoplasmic 2 [KO:K05692]
102988905  actin, cytoplasmic 1 [KO:K05692]
112063645  actin, cytoplasmic 1 isoform X2 [KO:K05692]
102977546  LMNA; lamin isoform X1 [KO:K12641]
102995268  LMNB2; lamin-B2 [KO:K07611]
102981706  LMNB1; lamin-B1 [KO:K07611]
102996986  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
102981106  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
102986056  PARP3; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
114485949  DFFA; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
102975870  DNA fragmentation factor subunit alpha [KO:K02310]
102991557  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
102980034  ENDOG; endonuclease G, mitochondrial [KO:K01173]
102994580  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
102987670  serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
102996185  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
102984842  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102992034  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102984504  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
102976041  CAPN2; calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
102981822  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
102975968  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
102984157  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102979652  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
102980242  DNA damage-inducible transcript 3 protein-like [KO:K04452]
102983822  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
102977235  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102976155  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
102974243  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
102980378  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
112067373  procathepsin L isoform X1 [KO:K01365] [EC:3.4.22.15]
102996148  CTSL; procathepsin L isoform X2 [KO:K01365] [EC:3.4.22.15]
102974923  procathepsin L isoform X1 [KO:K01365] [EC:3.4.22.15]
102988543  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
102995376  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
102979785  CTSS; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
102979042  CTSW; cathepsin W isoform X4 [KO:K08569] [EC:3.4.22.-]
102993000  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
102981700  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
102981991  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
102978378  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
102977574  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
102976319  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
102980439  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
102987942  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
102986746  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
102985812  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102982845  disabled homolog 2-interacting protein [KO:K19901]
102976909  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
102996353  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
102977417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102984741  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102974655  BAD; bcl2-associated agonist of cell death [KO:K02158]
102975458  JUN; transcription factor Jun [KO:K04448]
102982453  FOS; protein c-Fos [KO:K04379]
102985658  TP53; cellular tumor antigen p53 [KO:K04451]
112064066  HRK; activator of apoptosis harakiri [KO:K02512]
102991269  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102977668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
102976706  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
114485485  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
102980964  IKBKG; NF-kappa-B essential modulator [KO:K07210]
102973672  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102981135  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102974198  RELA; transcription factor p65 isoform X1 [KO:K04735]
102976345  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
102974987  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102993403  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102986518  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102979844  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
102981932  BCL2A1; bcl-2-related protein A1 [KO:K02162]
102975752  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102974584  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
102976277  bcl-2-binding component 3, isoforms 1/2 [KO:K10132]
102980477  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
102982974  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
102988669  NGF; beta-nerve growth factor isoform X2 [KO:K02582]
102990275  NTRK1; high affinity nerve growth factor receptor isoform X2 [KO:K03176] [EC:2.7.10.1]
102973496  interleukin-3 [KO:K04736]
102987302  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
102996201  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
102986098  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102978952  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102977108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102975555  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102991779  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102991192  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102977392  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102981524  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102976971  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
102990087  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102994715  HRAS; GTPase HRas isoform X2 [KO:K02833]
102977125  KRAS; GTPase KRas isoform X1 [KO:K07827]
102992439  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
102982641  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
102987866  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
102992191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102994150  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102989074  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
pcad04010  MAPK signaling pathway
pcad04020  Calcium signaling pathway
pcad04064  NF-kappa B signaling pathway
pcad04115  p53 signaling pathway
pcad04141  Protein processing in endoplasmic reticulum
pcad04151  PI3K-Akt signaling pathway
pcad04650  Natural killer cell mediated cytotoxicity
pcad04668  TNF signaling pathway
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system