KEGG   PATHWAY: achc04210
Entry
achc04210                   Pathway                                
Name
Apoptosis - Aquila chrysaetos chrysaetos (golden eagle)
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
achc04210  Apoptosis
achc04210

Other DBs
GO: 0006915
Organism
Aquila chrysaetos chrysaetos (golden eagle) [GN:achc]
Gene
115333440  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
115333630  [KO:K04725] [EC:2.3.2.27]
115333742  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
115333806  FOS; LOW QUALITY PROTEIN: proto-oncogene c-Fos [KO:K04379]
115334063  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
115334762  NGF; beta-nerve growth factor [KO:K02582]
115334771  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
115334876  [KO:K19901]
115335082  [KO:K07374]
115335157  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
115335295  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X9 [KO:K06114]
115335300  ENDOG; endonuclease G, mitochondrial [KO:K01173]
115335375  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
115335383  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
115335439  NRAS; GTPase NRas isoform X1 [KO:K07828]
115335528  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
115335879  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
115336033  ACTB; actin, cytoplasmic 1 [KO:K05692]
115336106  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
115336644  LMNB1; lamin-B1 isoform X1 [KO:K07611]
115336971  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
115337134  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
115337302  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
115337331  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
115337413  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
115337438  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
115338040  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
115338049  [KO:K04456] [EC:2.7.11.1]
115338050  [KO:K04456] [EC:2.7.11.1]
115338264  TP53; LOW QUALITY PROTEIN: cellular tumor antigen p53 [KO:K04451]
115338336  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
115338798  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
115338811  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
115339188  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
115339645  [KO:K08738]
115340949  ACTG1; actin, cytoplasmic 2 [KO:K05692]
115341198  [KO:K07611]
115341255  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
115341473  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
115341718  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
115341771  [KO:K07374]
115341772  [KO:K07374]
115341775  [KO:K05692]
115341996  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
115342153  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
115342320  BCL2A1; bcl-2-related protein A1 [KO:K02162]
115342450  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
115342550  [KO:K04398] [EC:3.4.22.61]
115342598  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
115342629  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
115342697  [KO:K08731]
115342707  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
115342842  [KO:K07374]
115342843  [KO:K07374]
115342979  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
115343190  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
115343323  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
115343325  CFLAR; LOW QUALITY PROTEIN: CASP8 and FADD-like apoptosis regulator [KO:K04724]
115343326  [KO:K04398] [EC:3.4.22.61]
115343397  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
115343515  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X2 [KO:K03158]
115343994  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
115344910  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
115344950  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
115344983  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
115345326  DIABLO; diablo homolog, mitochondrial [KO:K10522]
115345406  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
115345514  MCL1; LOW QUALITY PROTEIN: induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
115345553  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
115345557  [KO:K01368] [EC:3.4.22.27]
115345558  [KO:K01368] [EC:3.4.22.27]
115345622  HRK; LOW QUALITY PROTEIN: activator of apoptosis harakiri [KO:K02512]
115345654  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
115346053  LMNA; lamin [KO:K12641]
115346261  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
115346841  [KO:K16943]
115347173  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
115347305  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
115347472  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
115347788  [KO:K07374]
115347910  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
115347960  CASP7; caspase-7 isoform X2 [KO:K04397] [EC:3.4.22.60]
115347976  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
115348312  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
115348471  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
115348644  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
115348746  JUN; transcription factor AP-1 [KO:K04448]
115348827  LMNB2; lamin-B2 [KO:K07611]
115348869  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
115348975  [KO:K02649]
115349144  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
115349300  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
115349310  [KO:K01365] [EC:3.4.22.15]
115349575  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
115349650  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
115349915  [KO:K04397] [EC:3.4.22.60]
115349962  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
115350118  [KO:K04722]
115350124  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
115350221  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
115350251  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
115350343  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
115350500  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
115350923  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
115351083  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
115351636  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
115351779  PIDD1; p53-induced death domain-containing protein 1 isoform X2 [KO:K10130]
115351819  HRAS; GTPase HRas [KO:K02833]
115351998  FADD; FAS-associated death domain protein [KO:K02373]
115352336  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
115352454  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
115352540  KRAS; GTPase KRas isoform X2 [KO:K07827]
115352588  [KO:K07374]
115352590  [KO:K07374]
115352694  [KO:K04738]
115352740  BID; BH3-interacting domain death agonist isoform X2 [KO:K04726]
115352756  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
115353069  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
115353096  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
115353209  [KO:K16060]
115353268  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
115353494  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
115353614  PARP4; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
115353680  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
115353699  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121233034  [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
achc04010  MAPK signaling pathway
achc04020  Calcium signaling pathway
achc04115  p53 signaling pathway
achc04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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