KEGG   PATHWAY: oro04210
Entry
oro04210                    Pathway                                
Name
Apoptosis - Odobenus rosmarus divergens (Pacific walrus)
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
oro04210  Apoptosis
oro04210

Other DBs
GO: 0006915
Organism
Odobenus rosmarus divergens (Pacific walrus) [GN:oro]
Gene
101371152  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
101381319  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
101369551  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
101385048  FADD; FAS-associated death domain protein [KO:K02373]
101368209  TNF; tumor necrosis factor [KO:K03156]
101386839  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101368290  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X2 [KO:K03171]
101366831  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
101365855  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101366538  CASP10; caspase-10 isoform X2 [KO:K04400] [EC:3.4.22.63]
101375690  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
101371336  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
101363955  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
101371120  BID; BH3-interacting domain death agonist [KO:K04726]
101371652  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
101380231  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101372352  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
101382516  SEPT4; septin-4 isoform X1 [KO:K16943]
101375505  LOW QUALITY PROTEIN: serine protease HTRA2, mitochondrial-like [KO:K08669] [EC:3.4.21.108]
101382419  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
101386882  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
101386944  cytochrome c [KO:K08738]
101383104  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
101362812  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
101369174  PRF1; perforin-1 [KO:K07818]
101370515  granzyme B [KO:K01353] [EC:3.4.21.79]
101383301  duodenase-1-like [KO:K01353] [EC:3.4.21.79]
101367064  tubulin alpha-1A chain isoform X3 [KO:K07374]
101367544  tubulin alpha-1B chain-like isoform X2 [KO:K07374]
101367842  tubulin alpha-1B chain [KO:K07374]
101366680  tubulin alpha-3 chain [KO:K07374]
101367253  tubulin alpha-3 chain-like [KO:K07374]
101372594  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
101380811  LOW QUALITY PROTEIN: tubulin alpha chain-like [KO:K07374]
101379370  TUBAL3; LOW QUALITY PROTEIN: tubulin alpha chain-like 3 [KO:K07374]
101379814  TUBA4A; tubulin alpha-4A chain [KO:K07374]
101371240  tubulin alpha-8 chain [KO:K07374]
101368348  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
101376217  induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
101375328  ACTB; actin, cytoplasmic 1 isoform X2 [KO:K05692]
101384457  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
101383303  LMNA; lamin isoform X1 [KO:K12641]
101364166  LMNB2; lamin-B2 [KO:K07611]
101371343  LMNB1; lamin-B1 isoform X1 [KO:K07611]
101371045  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
101366871  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
101374159  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
101375131  PARP2; poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
101386624  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
101367274  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
101382363  ENDOG; endonuclease G, mitochondrial [KO:K01173]
101382897  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
101371113  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
101371938  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101367743  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101377380  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101380808  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
101386731  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
101364547  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
101382304  caspase-12-like [KO:K04741] [EC:3.4.22.-]
101365565  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
101363609  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
101368122  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101380889  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
101375531  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
101371731  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
101381080  CTSD; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
101365457  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
101362840  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
101371209  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
101362126  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
101364724  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101382346  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101364428  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101379477  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
101370623  CTSS; cathepsin S isoform X2 [KO:K01368] [EC:3.4.22.27]
101377645  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
101365974  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
101372845  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
101373139  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101367150  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
101363894  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
101378922  BCL2L11; bcl-2-like protein 11 isoform X2 [KO:K16341]
101380440  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101372267  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101377893  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
101363053  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101368086  DAB2IP; LOW QUALITY PROTEIN: disabled homolog 2-interacting protein [KO:K19901]
101374728  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
101367488  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101374143  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
101376185  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
101375422  BAD; bcl2-associated agonist of cell death [KO:K02158]
101368207  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
101366773  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
101362427  TP53; cellular tumor antigen p53 [KO:K04451]
101377276  HRK; activator of apoptosis harakiri [KO:K02512]
101363246  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101364103  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101375346  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101384959  IKBKG; NF-kappa-B essential modulator isoform X2 [KO:K07210]
101384149  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101371488  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101381225  RELA; transcription factor p65 [KO:K04735]
101366412  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
101374376  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
101374334  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101363875  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101364536  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
101384910  BCL2A1; bcl-2-related protein A1 [KO:K02162]
101378264  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101365003  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
101366869  BBC3; bcl-2-binding component 3 [KO:K10132]
101362130  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
101384305  CASP2; caspase-2 isoform X2 [KO:K02186] [EC:3.4.22.55]
101384791  NGF; beta-nerve growth factor [KO:K02582]
101374117  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
101383763  IL3RA; LOW QUALITY PROTEIN: interleukin-3 receptor subunit alpha [KO:K04737]
101363658  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
101370689  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101385241  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101385267  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101374787  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101370100  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101371800  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101378353  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
101383166  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101382320  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101374757  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101367134  GTPase HRas-like [KO:K02833]
101372786  HRAS; GTPase HRas isoform X1 [KO:K02833]
101370458  KRAS; GTPase KRas isoform X2 [KO:K07827]
101363525  NRAS; GTPase NRas [KO:K07828]
101372149  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101365373  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101376586  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101372573  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101382213  MAPK3; mitogen-activated protein kinase 3 isoform X1 [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
oro04010  MAPK signaling pathway
oro04020  Calcium signaling pathway
oro04064  NF-kappa B signaling pathway
oro04115  p53 signaling pathway
oro04141  Protein processing in endoplasmic reticulum
oro04151  PI3K-Akt signaling pathway
oro04650  Natural killer cell mediated cytotoxicity
oro04668  TNF signaling pathway
KO pathway
ko04210   
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