KEGG   PATHWAY: pcoq04210
Entry
pcoq04210                   Pathway                                
Name
Apoptosis - Propithecus coquereli (Coquerel's sifaka)
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
pcoq04210  Apoptosis
pcoq04210

Other DBs
GO: 0006915
Organism
Propithecus coquereli (Coquerel's sifaka) [GN:pcoq]
Gene
105806953  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
105825241  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
105826925  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
105807185  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
105821114  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
105822691  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
105827473  FADD; FAS-associated death domain protein [KO:K02373]
105817905  TNF; tumor necrosis factor isoform X1 [KO:K03156]
105805081  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
105823400  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
105819401  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
105819477  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105819115  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
105818980  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
105810111  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105826018  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
105815816  BID; BH3-interacting domain death agonist [KO:K04726]
105809316  BAX; apoptosis regulator BAX [KO:K02159]
105821684  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105825653  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
105813672  uncharacterized protein C17orf47 homolog [KO:K16943]
105813674  SEPT4; septin-4 isoform X1 [KO:K16943]
105821488  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
105812509  cytochrome c-like [KO:K08738]
105807375  cytochrome c, somatic [KO:K08738]
105815609  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
105810555  cytochrome c-like [KO:K08738]
105826075  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
105825008  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105821806  PRF1; perforin-1 [KO:K07818]
105812752  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
105819624  tubulin alpha-8 chain-like [KO:K07374]
105826892  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
105808789  TUBA4A; tubulin alpha-4A chain isoform X1 [KO:K07374]
105815384  TUBA1A; tubulin alpha-1A chain isoform X1 [KO:K07374]
105815399  tubulin alpha chain-like [KO:K07374]
105815409  tubulin alpha-1C chain [KO:K07374]
105815498  tubulin alpha-1B chain-like [KO:K07374]
105815811  TUBA8; tubulin alpha-8 chain [KO:K07374]
105815885  tubulin alpha chain-like [KO:K07374]
105821931  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
105822480  induced myeloid leukemia cell differentiation protein Mcl-1-like [KO:K02539]
105819999  ACTG1; actin, cytoplasmic 2 [KO:K05692]
105805953  ACTB; actin, cytoplasmic 1 [KO:K05692]
105806574  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
105821834  LMNA; lamin [KO:K12641]
105826355  LMNB1; lamin-B1 [KO:K07611]
105811981  LMNB2; lamin-B2 [KO:K07611]
105810394  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
105808109  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
105814392  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
105814512  PARP2; poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
105824986  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
105823006  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
105806593  ENDOG; endonuclease G, mitochondrial [KO:K01173]
105817653  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
105825063  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
105818690  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
105812706  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
105807599  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105821681  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105827335  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
105810138  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
105810299  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
105819858  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
105815896  LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2 subunit 1-like [KO:K03237]
105805232  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105816363  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
105811637  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
105808237  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
105816553  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
105827466  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
105822761  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
105821962  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
105822404  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
105816430  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
105811126  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
105821963  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
105827350  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
105820086  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
105822276  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
105822279  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
105826835  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
105824013  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
105808300  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
105814728  bcl-2-like protein 1 isoform X1 [KO:K04570]
105804942  BCL2L1; bcl-2-like protein 1 [KO:K04570]
105811149  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105821682  DAXX; death domain-associated protein 6 [KO:K02308]
105816051  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
105826457  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
105827162  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
105823643  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105812700  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105815999  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
105827296  BAD; bcl2-associated agonist of cell death [KO:K02158]
105806347  JUN; transcription factor AP-1 [KO:K04448]
105819831  FOS; proto-oncogene c-Fos [KO:K04379]
105819395  TP53; cellular tumor antigen p53 [KO:K04451]
105825191  HRK; activator of apoptosis harakiri [KO:K02512]
105824147  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
105824261  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
105819687  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105824538  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105821530  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105819191  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105827383  RELA; transcription factor p65 isoform X1 [KO:K04735]
105812704  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
105811966  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105817781  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105817934  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105826431  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
105823014  BCL2A1; bcl-2-related protein A1 [KO:K02162]
105822182  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
105816535  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
105817577  BBC3; bcl-2-binding component 3 [KO:K10132]
105816366  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
105815440  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
105810582  NGF; beta-nerve growth factor [KO:K02582]
105821881  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
105820355  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
105805213  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
105824997  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105826540  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105806240  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105826612  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105818191  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105814042  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105813132  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105820591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105812606  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105810397  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105816561  HRAS; GTPase HRas isoform X1 [KO:K02833]
105807545  KRAS; GTPase KRas [KO:K07827]
105810591  NRAS; GTPase NRas [KO:K07828]
105819002  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105810783  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105811965  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105823104  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105810199  MAPK1; mitogen-activated protein kinase 1 [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
pcoq04010  MAPK signaling pathway
pcoq04020  Calcium signaling pathway
pcoq04064  NF-kappa B signaling pathway
pcoq04115  p53 signaling pathway
pcoq04141  Protein processing in endoplasmic reticulum
pcoq04151  PI3K-Akt signaling pathway
pcoq04650  Natural killer cell mediated cytotoxicity
pcoq04668  TNF signaling pathway
KO pathway
ko04210   
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