KEGG   PATHWAY: nvs04210
Entry
nvs04210                    Pathway                                
Name
Apoptosis - Neogale vison (American mink)
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
nvs04210  Apoptosis
nvs04210

Other DBs
GO: 0006915
Organism
Neogale vison (American mink) [GN:nvs]
Gene
122889094  [KO:K04726]
122889271  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
122889330  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
122889447  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
122889452  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122889708  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
122889856  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
122889990  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
122890296  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
122891087  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
122891540  BID; BH3-interacting domain death agonist [KO:K04726]
122891693  TUBAL3; LOW QUALITY PROTEIN: tubulin alpha chain-like 3 [KO:K07374]
122891729  [KO:K04736]
122891883  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
122891924  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
122892226  LMNB1; lamin-B1 [KO:K07611]
122892446  KRAS; GTPase KRas isoform X1 [KO:K07827]
122892476  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
122892505  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
122892516  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
122892569  TUBA1A; tubulin alpha-1A chain [KO:K07374]
122892570  [KO:K07374]
122892581  TUBA1B; tubulin alpha-1B chain [KO:K07374]
122892638  TUBA8; tubulin alpha-8 chain [KO:K07374]
122892965  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
122893137  [KO:K01353] [EC:3.4.21.79]
122893478  FOS; proto-oncogene c-Fos [KO:K04379]
122893529  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
122893621  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
122893665  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
122893967  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
122894172  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122894276  BCL2A1; bcl-2-related protein A1 [KO:K02162]
122894512  [KO:K01353] [EC:3.4.21.79]
122895342  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122895932  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
122895995  ACTB; actin, cytoplasmic 1 [KO:K05692]
122896393  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
122896474  [KO:K04725] [EC:2.3.2.27]
122896478  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
122897563  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
122897974  [KO:K07374]
122898912  PRF1; perforin-1 [KO:K07818]
122899136  [KO:K07828]
122899371  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
122899425  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122899438  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
122899479  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
122899916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122899945  TNF; tumor necrosis factor isoform X1 [KO:K03156]
122900023  JUN; transcription factor AP-1 [KO:K04448]
122900071  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122900359  NRAS; GTPase NRas [KO:K07828]
122900366  NGF; beta-nerve growth factor [KO:K02582]
122900432  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
122900434  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
122900437  MCL1; LOW QUALITY PROTEIN: induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
122900656  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
122900866  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122901015  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
122901125  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
122902187  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
122902189  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
122902190  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
122902333  [KO:K07374]
122902631  [KO:K08738]
122902835  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
122902845  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
122902991  [KO:K08738]
122903050  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
122903183  [KO:K07374]
122903185  [KO:K07374]
122903200  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122903387  HRK; activator of apoptosis harakiri [KO:K02512]
122904917  [KO:K08738]
122905159  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
122905894  ACTG1; actin, cytoplasmic 2 [KO:K05692]
122905937  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
122906080  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
122906116  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
122906270  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
122906527  SEPTIN4; septin-4 isoform X1 [KO:K16943]
122906719  TP53; cellular tumor antigen p53 [KO:K04451]
122906893  PARP4; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
122908700  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
122908712  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122908899  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122909192  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122909251  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
122909376  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
122909588  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122909871  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122909911  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122909916  LMNB2; lamin-B2 [KO:K07611]
122910530  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
122910577  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
122910778  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
122911360  NOL3; nucleolar protein 3 [KO:K28177]
122911363  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
122911843  BAX; apoptosis regulator BAX [KO:K02159]
122911902  BBC3; bcl-2-binding component 3 [KO:K10132]
122912036  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122912225  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
122912245  [KO:K04741] [EC:3.4.22.-]
122912257  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
122912258  [KO:K16060]
122912358  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
122912507  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
122913061  BAD; bcl2-associated agonist of cell death [KO:K02158]
122913101  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
122913121  RELA; transcription factor p65 [KO:K04735]
122913130  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
122913159  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
122913220  HRAS; GTPase HRas isoform X1 [KO:K02833]
122913228  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
122913243  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
122913256  [KO:K04722]
122913265  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
122915023  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
122915073  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
122915099  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
122915651  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122915931  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
122916174  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
122916755  [KO:K01365] [EC:3.4.22.15]
122916992  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122917083  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
122917190  ENDOG; endonuclease G, mitochondrial [KO:K01173]
122917196  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
122917293  [KO:K19901]
122917303  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
122917617  [KO:K01365] [EC:3.4.22.15]
122917636  [KO:K01365] [EC:3.4.22.15]
122917637  [KO:K01365] [EC:3.4.22.15]
122917638  [KO:K01365] [EC:3.4.22.15]
122918121  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
122918287  LMNA; lamin [KO:K12641]
122918316  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
122918524  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122918680  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
122918704  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
122918800  [KO:K07374]
122918946  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
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
Reference
PMID:36652128
  Authors
Liu K, Lan D, Li C, Liu S, Dai X, Song T, Wang X, Kong Q, He Z, Tan J, Zhang J
  Title
A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.
  Journal
Apoptosis 28:313-325 (2023)
DOI:10.1007/s10495-022-01802-4
Related
pathway
nvs04010  MAPK signaling pathway
nvs04020  Calcium signaling pathway
nvs04064  NF-kappa B signaling pathway
nvs04115  p53 signaling pathway
nvs04141  Protein processing in endoplasmic reticulum
nvs04151  PI3K-Akt signaling pathway
nvs04650  Natural killer cell mediated cytotoxicity
nvs04668  TNF signaling pathway
KO pathway
ko04210   

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