KEGG   PATHWAY: mpuf04210
Entry
mpuf04210                   Pathway                                
Name
Apoptosis - Mustela putorius furo (domestic ferret)
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
mpuf04210  Apoptosis
mpuf04210

Other DBs
GO: 0006915
Organism
Mustela putorius furo (domestic ferret) [GN:mpuf]
Gene
101675328  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
101687517  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
101677976  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
101671860  FADD; FAS-associated death domain protein [KO:K02373]
101687148  TNF; tumor necrosis factor isoform X1 [KO:K03156]
101676562  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101690408  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
101675551  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
101678102  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
101685031  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
101685585  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
101690858  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
101683818  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
101686636  BID; BH3-interacting domain death agonist [KO:K04726]
101681070  BH3-interacting domain death agonist-like [KO:K04726]
101686802  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
101688916  BAK1; bcl-2 homologous antagonist/killer isoform X3 [KO:K14021]
101679356  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
101687008  uncharacterized protein C17orf47 isoform X1 [KO:K16943]
101681959  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
106003371  cytochrome c, testis-specific [KO:K08738]
101690488  cytochrome c [KO:K08738]
101691091  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
101681290  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
101688524  PRF1; perforin-1 isoform X1 [KO:K07818]
101693455  granzyme B [KO:K01353] [EC:3.4.21.79]
101678877  tubulin alpha-8 chain [KO:K07374]
101692890  tubulin alpha-1A chain-like [KO:K07374]
101679966  tubulin alpha-1C chain [KO:K07374]
101680178  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
101680276  tubulin alpha-1B chain [KO:K07374]
101675663  TUBA3E; tubulin alpha-3E chain isoform X1 [KO:K07374]
101689201  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
101677236  TUBA4A; tubulin alpha-4A chain [KO:K07374]
101685396  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
101679540  ACTG1; actin, cytoplasmic 2 [KO:K05692]
101686268  ACTB; actin, cytoplasmic 1 [KO:K05692]
101679779  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
101685893  LMNA; lamin [KO:K12641]
101679686  LMNB1; lamin-B1 [KO:K07611]
101671833  LMNB2; lamin-B2 [KO:K07611]
101688592  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070] [EC:2.4.2.30]
101680699  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
101670450  PARP2; poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
101671228  PARP4; poly [ADP-ribose] polymerase 4 isoform X1 [KO:K10798] [EC:2.4.2.30]
101679703  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
101670402  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
101670029  ENDOG; endonuclease G, mitochondrial [KO:K01173]
101691512  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
101689378  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
101691230  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
101677799  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101684131  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101688102  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101689283  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
101675244  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
101670985  caspase-12-like [KO:K04741] [EC:3.4.22.-]
101689747  EIF2AK3; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
101692556  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
101680524  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101694124  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
101684783  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
101694438  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
101681849  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
101690754  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
101679490  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
101674358  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
101682378  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
101673105  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101674158  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101687698  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
101673257  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
101683261  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
101671010  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
101685427  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
101691821  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101692293  baculoviral IAP repeat-containing protein 3 [KO:K16060]
101671154  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
101676477  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
101683234  BCL2L11; bcl-2-like protein 11 isoform X6 [KO:K16341]
101674297  BCL2L1; bcl-2-like protein 1 [KO:K04570]
101681308  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101684105  DAXX; death domain-associated protein 6 isoform X3 [KO:K02308]
101685502  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101675309  DAB2IP; disabled homolog 2-interacting protein isoform X3 [KO:K19901]
101686402  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
101672072  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101681349  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101676423  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101686427  BAD; bcl2-associated agonist of cell death [KO:K02158]
101680348  JUN; transcription factor AP-1 [KO:K04448]
101685236  FOS; proto-oncogene c-Fos [KO:K04379]
101677794  TP53; cellular tumor antigen p53 [KO:K04451]
101688261  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101680658  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101686932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101671648  IKBKG; NF-kappa-B essential modulator [KO:K07210]
101693829  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101680542  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101680239  RELA; transcription factor p65 [KO:K04735]
101680477  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X6 [KO:K02374]
101674139  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101693694  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101678248  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101682095  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
101677701  BCL2A1; bcl-2-related protein A1 [KO:K02162]
101673428  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101690569  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
101692767  BBC3; bcl-2-binding component 3 [KO:K10132]
101694272  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
101674782  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
101694006  NGF; beta-nerve growth factor [KO:K02582]
101684239  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
101678790  interleukin-3 [KO:K04736]
101671295  IL3RA; interleukin-3 receptor subunit alpha isoform X2 [KO:K04737]
101670777  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
101681650  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101676567  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101684443  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101680399  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101683594  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
101683710  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101687213  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101679776  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101687324  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101676895  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101681355  HRAS; GTPase HRas isoform X1 [KO:K02833]
101681333  KRAS; GTPase KRas isoform X3 [KO:K07827]
101683038  NRAS; GTPase NRas [KO:K07828]
101690482  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101680975  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101678743  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101679748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101671073  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
mpuf04010  MAPK signaling pathway
mpuf04020  Calcium signaling pathway
mpuf04064  NF-kappa B signaling pathway
mpuf04115  p53 signaling pathway
mpuf04141  Protein processing in endoplasmic reticulum
mpuf04151  PI3K-Akt signaling pathway
mpuf04650  Natural killer cell mediated cytotoxicity
mpuf04668  TNF signaling pathway
KO pathway
ko04210   
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