KEGG   PATHWAY: aamp04210
Entry
aamp04210                   Pathway                                
Name
Apoptosis - Arvicola amphibius (Eurasian water vole)
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
aamp04210  Apoptosis
aamp04210

Other DBs
GO: 0006915
Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119799550  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
119799760  Ctsb; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
119799946  [KO:K04722]
119799953  [KO:K01353] [EC:3.4.21.79]
119800102  [KO:K01353] [EC:3.4.21.79]
119800130  [KO:K01353] [EC:3.4.21.79]
119800145  [KO:K01353] [EC:3.4.21.79]
119800183  Parp4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
119800194  Parp2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
119800249  Hras; GTPase HRas isoform X1 [KO:K02833]
119800869  Ntrk1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
119800874  Mcl1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
119801102  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
119801207  Ngf; beta-nerve growth factor [KO:K02582]
119801328  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
119801338  Casp6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
119801374  Ctss; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
119801375  Lmna; lamin [KO:K12641]
119801495  Lmnb2; lamin-B2 [KO:K07611]
119801497  Nras; GTPase NRas [KO:K07828]
119801899  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
119802088  Pidd1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
119802120  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
119802203  Fadd; FAS-associated death domain protein [KO:K02373]
119802317  Nol3; nucleolar protein 3 [KO:K28177]
119802627  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
119803098  Ctsc; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
119803285  Ddit3; DNA damage-inducible transcript 3 protein [KO:K04452]
119803346  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
119803437  Rela; transcription factor p65 isoform X1 [KO:K04735]
119803853  Cflar; LOW QUALITY PROTEIN: CASP8 and FADD-like apoptosis regulator [KO:K04724]
119803862  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
119804230  [KO:K07827]
119804312  Casp7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
119804616  [KO:K04725] [EC:2.3.2.27]
119804668  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
119804745  Aifm1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
119804936  Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
119805855  [KO:K07374]
119805902  [KO:K04366] [EC:2.7.11.1]
119806213  Itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
119806318  Kras; GTPase KRas isoform X1 [KO:K07827]
119806390  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
119806400  [KO:K07374]
119806404  [KO:K07374]
119806482  Bid; BH3-interacting domain death agonist [KO:K04726]
119806674  Tuba8; tubulin alpha-8 chain [KO:K07374]
119806736  Htra2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
119806861  Casp2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
119807481  [KO:K08738]
119807493  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
119807948  [KO:K08738]
119808154  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
119808167  Eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
119808272  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
119808979  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119808996  Bcl2a1; bcl-2-related protein A1 [KO:K02162]
119809052  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
119809564  [KO:K16060]
119809603  Ctsh; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
119809632  Birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
119809903  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119810453  Parp3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
119810503  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119811081  Actg1; actin, cytoplasmic 2 [KO:K05692]
119811270  Mapk9; LOW QUALITY PROTEIN: mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
119812025  Ern1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
119812102  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119812257  Septin4; septin-4 isoform X1 [KO:K16943]
119812324  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
119812378  [KO:K08738]
119812503  [KO:K08738]
119812861  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
119812960  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
119813044  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
119813356  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119813419  Tp53; cellular tumor antigen p53 [KO:K04451]
119813574  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
119813599  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
119814226  Ctsz; cathepsin Z [KO:K08568] [EC:3.4.18.1]
119814257  [KO:K04737]
119814843  Ctsw; cathepsin W [KO:K08569] [EC:3.4.22.-]
119814996  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
119815469  Lmnb1; lamin-B1 [KO:K07611]
119815691  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
119815786  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
119816315  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119816335  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
119816423  Dffb; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
119816668  Dffa; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
119816683  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
119816694  Jun; transcription factor AP-1 [KO:K04448]
119816942  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
119817489  Tubal3; tubulin alpha chain-like 3 [KO:K07374]
119817619  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
119817631  Ctsv; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
119817743  [KO:K02649]
119818545  Ctsf; cathepsin F [KO:K01373] [EC:3.4.22.41]
119818608  [KO:K04451]
119818610  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
119818643  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119818726  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
119818763  [KO:K19901]
119818958  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
119819008  [KO:K08738]
119819161  Fos; proto-oncogene c-Fos [KO:K04379]
119819361  Traf1; TNF receptor-associated factor 1 [KO:K03172]
119819574  Sptan1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
119819667  Endog; endonuclease G, mitochondrial [KO:K01173]
119820487  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119820525  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
119820587  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
119820729  Bbc3; bcl-2-binding component 3 [KO:K10132]
119821363  Tuba4a; tubulin alpha-4A chain isoform X1 [KO:K07374]
119822305  [KO:K07374]
119822349  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
119822381  Tuba1a; tubulin alpha-1A chain [KO:K07374]
119822383  [KO:K07374]
119822506  Tnf; tumor necrosis factor [KO:K03156]
119822546  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
119822854  Daxx; death domain-associated protein 6 [KO:K02308]
119823109  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
119823231  Prf1; perforin-1 [KO:K07818]
119823378  Csf2rb; cytokine receptor common subunit beta [KO:K04738]
119823918  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
119824565  Hrk; activator of apoptosis harakiri [KO:K02512]
119824680  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119824935  Diablo; diablo homolog, mitochondrial [KO:K10522]
119825660  Actb; actin, cytoplasmic 1 [KO:K05692]
119825663  Ptpn13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
119826317  Pik3ca; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119826387  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
119826593  Ctso; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
119827246  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119827427  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
119827467  Capn1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
119827491  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119827640  [KO:K08738]
119827718  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
119827881  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
119827962  Parp1; poly [ADP-ribose] polymerase 1 [KO:K24070]
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
aamp04010  MAPK signaling pathway
aamp04020  Calcium signaling pathway
aamp04064  NF-kappa B signaling pathway
aamp04115  p53 signaling pathway
aamp04141  Protein processing in endoplasmic reticulum
aamp04151  PI3K-Akt signaling pathway
aamp04650  Natural killer cell mediated cytotoxicity
aamp04668  TNF signaling pathway
KO pathway
ko04210   

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