KEGG   PATHWAY: oga04210
Entry
oga04210                    Pathway                                
Name
Apoptosis - Otolemur garnettii (small-eared galago)
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
oga04210  Apoptosis
oga04210

Other DBs
GO: 0006915
Organism
Otolemur garnettii (small-eared galago) [GN:oga]
Gene
100958512  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
100960488  tumor necrosis factor receptor superfamily member 10A [KO:K04722]
100951008  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
100957582  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
100960309  FADD; FAS-associated death domain protein [KO:K02373]
100963613  TNF; tumor necrosis factor [KO:K03156]
100955892  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100952230  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
100966424  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
100965468  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
100965785  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
100950644  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
100961435  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100942180  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
100960302  BID; BH3-interacting domain death agonist [KO:K04726]
100957285  BAX; apoptosis regulator BAX [KO:K02159]
100941755  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105887594  DIABLO; diablo homolog, mitochondrial [KO:K10522]
100940425  SEPT4; septin-4 isoform X1 [KO:K16943]
100965412  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
100952744  cytochrome c, somatic [KO:K08738]
100946237  cytochrome c [KO:K08738]
100961637  cytochrome c, testis-specific [KO:K08738]
100951508  cytochrome c-like [KO:K08738]
100959812  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
100957904  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
100945002  PRF1; LOW QUALITY PROTEIN: perforin-1 [KO:K07818]
100957079  cathepsin G-like [KO:K01353] [EC:3.4.21.79]
100959107  cathepsin G-like [KO:K01353] [EC:3.4.21.79]
100957699  granzyme B-like [KO:K01353] [EC:3.4.21.79]
100961499  granzyme B [KO:K01353] [EC:3.4.21.79]
100957388  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
100947302  tubulin alpha-1B chain-like [KO:K07374]
100963795  tubulin alpha-3 chain-like [KO:K07374]
100967214  TUBA8; tubulin alpha-8 chain [KO:K07374]
100941549  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
100963937  LOW QUALITY PROTEIN: tubulin alpha chain-like [KO:K07374]
100946318  tubulin alpha-1A chain [KO:K07374]
100954785  tubulin alpha-3 chain-like [KO:K07374]
100942888  TUBA4A; tubulin alpha-4A chain isoform X1 [KO:K07374]
100952786  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
100966429  actin, cytoplasmic 1-like [KO:K05692]
100953854  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100960800  ACTB; actin, cytoplasmic 1 [KO:K05692]
100948486  SPTAN1; LOW QUALITY PROTEIN: spectrin alpha chain, non-erythrocytic 1 [KO:K06114]
100950005  LMNA; lamin isoform X2 [KO:K12641]
100946614  LMNB2; lamin-B2 [KO:K07611]
100964928  LMNB1; lamin-B1 [KO:K07611]
100956597  PARP1; poly [ADP-ribose] polymerase 1 isoform X2 [KO:K24070] [EC:2.4.2.30]
100944755  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
100961771  PARP2; poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
100943137  PARP3; poly [ADP-ribose] polymerase 3 isoform X1 [KO:K10798] [EC:2.4.2.30]
100956505  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
100948423  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
100942843  ENDOG; endonuclease G, mitochondrial [KO:K01173]
100940431  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
100942489  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
100966378  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100964437  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100954512  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100942290  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100950762  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
100946093  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100954053  LOW QUALITY PROTEIN: caspase-12-like [KO:K04741] [EC:3.4.22.-]
100945512  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
100966174  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
100940993  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100956595  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
100952002  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
100960196  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
100959687  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
100947819  CTSF; LOW QUALITY PROTEIN: cathepsin F [KO:K01373] [EC:3.4.22.41]
100946905  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
100950359  CTSK; cathepsin K isoform X3 [KO:K01371] [EC:3.4.22.38]
100963673  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
100958924  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
100951115  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
100950667  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
100962615  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
100941345  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
100951387  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
100951719  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2-like [KO:K16060]
100950019  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100951522  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100961291  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
100947708  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
100953032  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100955447  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100966127  DAXX; death domain-associated protein 6 [KO:K02308]
100949124  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
100962130  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
100943232  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
100957169  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100967053  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100960275  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100962306  BAD; bcl2-associated agonist of cell death [KO:K02158]
100965098  JUN; transcription factor AP-1 [KO:K04448]
100953435  FOS; proto-oncogene c-Fos [KO:K04379]
100963622  TP53; cellular tumor antigen p53 [KO:K04451]
100947983  HRK; activator of apoptosis harakiri [KO:K02512]
100957606  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100949554  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100946157  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100958883  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100947991  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100951061  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100957990  RELA; transcription factor p65 isoform X3 [KO:K04735]
100962259  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
100946928  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100950782  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100950842  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X2 [KO:K04402]
100959720  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
100949091  BCL2A1; bcl-2-related protein A1 [KO:K02162]
100947578  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
100940692  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
100945413  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
100957322  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
100963099  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
100946218  NGF; beta-nerve growth factor [KO:K02582]
100940422  NTRK1; high affinity nerve growth factor receptor isoform X2 [KO:K03176] [EC:2.7.10.1]
100945479  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
100960327  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
100947138  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100953367  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100954109  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100956838  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
100952580  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
100949858  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100950210  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100959825  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100955276  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100945977  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100951644  HRAS; GTPase HRas isoform X1 [KO:K02833]
100953050  KRAS; GTPase KRas isoform X3 [KO:K07827]
100949583  NRAS; GTPase NRas isoform X1 [KO:K07828]
100941062  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100959926  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100956072  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X2 [KO:K04369] [EC:2.7.12.2]
100951533  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100957343  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
oga04010  MAPK signaling pathway
oga04020  Calcium signaling pathway
oga04064  NF-kappa B signaling pathway
oga04115  p53 signaling pathway
oga04141  Protein processing in endoplasmic reticulum
oga04151  PI3K-Akt signaling pathway
oga04650  Natural killer cell mediated cytotoxicity
oga04668  TNF signaling pathway
KO pathway
ko04210   
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