KEGG   PATHWAY: aang04210
Entry
aang04210                   Pathway                                
Name
Apoptosis - Anguilla anguilla (European eel)
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
aang04210  Apoptosis
aang04210

Other DBs
GO: 0006915
Organism
Anguilla anguilla (European eel) [GN:aang]
Gene
118206207  [KO:K03173] [EC:2.3.2.27]
118206252  [KO:K02649]
118206371  [KO:K04402]
118206372  gadd45ga; growth arrest and DNA-damage-inducible, gamma a isoform X1 [KO:K04402]
118206373  [KO:K04402]
118206414  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118206564  hdr; hematopoietic death receptor isoform X1 [KO:K04722]
118206636  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
118206713  prf1.5; perforin 1.5 isoform X1 [KO:K07818]
118206787  ctsla; cathepsin La isoform X1 [KO:K01365] [EC:3.4.22.15]
118206932  [KO:K07611]
118207064  [KO:K06114]
118207405  [KO:K04958]
118207533  birc5b; baculoviral IAP repeat-containing protein 5b [KO:K08731]
118207569  dffb; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
118207640  [KO:K14021]
118207705  si:ch211-112c15.8; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
118207855  casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
118207887  dffa; DNA fragmentation factor subunit alpha [KO:K02310]
118208082  [KO:K07374]
118208083  [KO:K07374]
118208164  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
118208214  tuba5; tubulin alpha 5 isoform X1 [KO:K07374]
118208260  nras; GTPase NRas [KO:K07828]
118208283  nfkbiab; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha b [KO:K04734]
118208607  ngfa; neurotrophin-7 [KO:K02582]
118208660  tuba1a; tubulin alpha-1A chain [KO:K07374]
118208664  [KO:K07374]
118209617  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
118209637  ctsl.1; cathepsin L.1 [KO:K01365] [EC:3.4.22.15]
118209642  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118209880  ctsc; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
118210103  atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
118210178  [KO:K16943]
118210407  diabloa; diablo, IAP-binding mitochondrial protein a isoform X1 [KO:K10522]
118210593  tuba2; tubulin, alpha 2 [KO:K07374]
118210597  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
118210668  raf1b; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118210923  ddit3; DNA damage-inducible transcript 3 protein isoform X1 [KO:K04452]
118210990  [KO:K08568] [EC:3.4.18.1]
118211053  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
118211291  bcl2l1; bcl-2-like protein 1 [KO:K04570]
118211319  parp3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
118211513  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
118211653  [KO:K02582]
118211835  [KO:K07374]
118212126  [KO:K04402]
118212127  [KO:K04402]
118212128  [KO:K04402]
118212138  june; LOW QUALITY PROTEIN: junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
118212152  [KO:K01365] [EC:3.4.22.15]
118212459  dab2ipb; DAB2 interacting protein b isoform X1 [KO:K19901]
118212607  ptpn13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
118212644  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118212769  [KO:K06114]
118212863  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118212877  [KO:K03853] [EC:3.4.22.53]
118212878  [KO:K03853] [EC:3.4.22.53]
118212933  traf2b; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
118213118  casp2; caspase-2 [KO:K02186] [EC:3.4.22.55]
118213211  [KO:K03173] [EC:2.3.2.27]
118213354  lmnb1; lamin-B1 [KO:K07611]
118213436  [KO:K07818]
118213458  [KO:K04722]
118213555  ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
118213703  [KO:K04724]
118213740  parp4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
118213845  [KO:K07374]
118213846  [KO:K07374]
118213847  [KO:K07374]
118213848  [KO:K07374]
118214013  [KO:K04398] [EC:3.4.22.61]
118214015  casp20; caspase 20, apoptosis-related cysteine peptidase isoform X1 [KO:K04398] [EC:3.4.22.61]
118214291  [KO:K08738]
118214352  eif2s1a; eukaryotic translation initiation factor 2 subunit 1a [KO:K03237]
118214689  zgc:153993; apoptosis regulator BAX [KO:K02159]
118214767  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
118215248  ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
118215356  [KO:K02833]
118215419  ctsh; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
118215439  pidd1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
118216291  napsa; napsin-A [KO:K01379] [EC:3.4.23.5]
118216302  [KO:K08731]
118216518  [KO:K05692]
118216525  zgc:55558; GTPase HRas [KO:K07827]
118216741  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
118216771  [KO:K04466] [EC:2.7.11.25]
118216823  [KO:K08852] [EC:2.7.11.1 3.1.26.-]
118217213  [KO:K06276] [EC:2.7.11.1]
118217257  atf4b; activating transcription factor 4b isoform X1 [KO:K04374]
118217359  csf2rb; cytokine receptor common subunit beta isoform X1 [KO:K04738]
118217377  baxa; BCL2 associated X, apoptosis regulator a [KO:K02159]
118217410  [KO:K07818]
118217556  [KO:K04379]
118217618  [KO:K04379]
118217744  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118217792  capn1a; calpain 1, (mu/I) large subunit a [KO:K01367] [EC:3.4.22.52]
118217793  capn2a; calpain 2, (m/II) large subunit a [KO:K03853] [EC:3.4.22.53]
118217861  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118218013  bcl2l11; bcl-2-like protein 11 [KO:K16341]
118218170  [KO:K08731]
118218267  [KO:K07374]
118218445  [KO:K03853] [EC:3.4.22.53]
118218446  capn8; calpain-8 [KO:K03853] [EC:3.4.22.53]
118218999  [KO:K07827]
118219247  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
118219756  [KO:K02159]
118220060  tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
118220191  atf4a; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
118220249  [KO:K04371] [EC:2.7.11.24]
118220367  ern2; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
118220445  casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
118220535  [KO:K01368] [EC:3.4.22.27]
118220615  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
118220627  [KO:K16341]
118220678  [KO:K05692]
118220681  [KO:K01367] [EC:3.4.22.52]
118220682  [KO:K03853] [EC:3.4.22.53]
118220815  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
118220848  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118220959  [KO:K03853] [EC:3.4.22.53]
118221018  [KO:K04456] [EC:2.7.11.1]
118221077  [KO:K01367] [EC:3.4.22.52]
118221088  fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
118221131  [KO:K02159]
118221302  [KO:K04738]
118221513  [KO:K04466] [EC:2.7.11.25]
118221918  [KO:K07374]
118221923  [KO:K07374]
118222447  casp10; caspase-8 isoform X1 [KO:K04400] [EC:3.4.22.63]
118222448  [KO:K04398] [EC:3.4.22.61]
118222860  ctsf; cathepsin F [KO:K01373] [EC:3.4.22.41]
118222872  [KO:K04724]
118222942  si:ch211-1i11.3; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
118222970  [KO:K07374]
118222971  [KO:K07374]
118223000  [KO:K04451]
118223522  rela; transcription factor p65 [KO:K04735]
118223556  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118223663  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118223847  [KO:K01353] [EC:3.4.21.79]
118223870  [KO:K08738]
118223971  [KO:K01353] [EC:3.4.21.79]
118224014  [KO:K02158]
118224103  xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
118224549  [KO:K04402]
118224763  gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402]
118224771  cts12; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
118224914  lmnb2; lamin-B2 [KO:K07611]
118224955  faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
118225426  [KO:K02161]
118225456  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
118225588  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
118225726  [KO:K00922] [EC:2.7.1.153]
118226119  [KO:K04721]
118226129  [KO:K02861] [EC:2.7.11.1]
118226171  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
118226257  [KO:K01365] [EC:3.4.22.15]
118226519  jun; transcription factor AP-1 [KO:K04448]
118226682  fadd; FAS-associated death domain protein [KO:K02373]
118226796  eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
118227344  [KO:K02580]
118227370  [KO:K12641]
118227505  tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
118227649  [KO:K08669] [EC:3.4.21.108]
118227896  [KO:K02833]
118228056  casp3a; caspase-3a isoform X1 [KO:K02187] [EC:3.4.22.56]
118228397  [KO:K01379] [EC:3.4.23.5]
118228463  lmnl3; lamin L3 isoform X1 [KO:K07611]
118228785  [KO:K04734]
118228853  [KO:K02649]
118228941  [KO:K04402]
118229023  [KO:K04456] [EC:2.7.11.1]
118229086  [KO:K04721]
118229166  [KO:K04379]
118229370  [KO:K04379]
118229512  gadd45aa; growth arrest and DNA-damage-inducible, alpha, a [KO:K04402]
118229817  [KO:K00922] [EC:2.7.1.153]
118230058  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
118230342  ctsba; cathepsin B [KO:K01363] [EC:3.4.22.1]
118230513  map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
118230631  parp1; poly [ADP-ribose] polymerase 1 [KO:K24070]
118231019  bida; BH3 interacting domain death agonist [KO:K04726]
118231090  [KO:K02187] [EC:3.4.22.56]
118231433  [KO:K04397] [EC:3.4.22.60]
118231742  [KO:K08669] [EC:3.4.21.108]
118231849  apaf1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
118231913  mcl1b; induced myeloid leukemia cell differentiation protein Mcl-1b [KO:K02539]
118232243  [KO:K04396] [EC:3.4.22.59]
118232502  [KO:K02580]
118232826  [KO:K08568] [EC:3.4.18.1]
118232957  daxx; death domain-associated protein 6 [KO:K02308]
118233231  [KO:K12641]
118233315  [KO:K02539]
118233400  [KO:K08738]
118233651  [KO:K01371] [EC:3.4.22.38]
118233652  [KO:K01371] [EC:3.4.22.38]
118233653  [KO:K01368] [EC:3.4.22.27]
118233655  [KO:K01368] [EC:3.4.22.27]
118233656  [KO:K01371] [EC:3.4.22.38]
118233657  [KO:K01368] [EC:3.4.22.27]
118233658  [KO:K01371] [EC:3.4.22.38]
118233659  [KO:K01371] [EC:3.4.22.38]
118233660  [KO:K01371] [EC:3.4.22.38]
118233789  [KO:K02161]
118234135  [KO:K07374]
118234166  ntrk1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
118234219  [KO:K01371] [EC:3.4.22.38]
118234220  [KO:K01371] [EC:3.4.22.38]
118234395  ripk1l; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
118234486  parp2; poly [ADP-ribose] polymerase 2 [KO:K28005]
118234601  [KO:K07818]
118234602  [KO:K07818]
118234603  [KO:K07818]
118234604  [KO:K07818]
118234823  [KO:K02158]
118234856  [KO:K16943]
118234986  si:dkeyp-50d11.2; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
118235210  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118235791  aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
118235846  tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
118236139  [KO:K04440] [EC:2.7.11.24]
118236176  [KO:K04735]
118236265  [KO:K10522]
118236468  [KO:K04456] [EC:2.7.11.1]
118236782  birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
118237064  traf1; TNF receptor-associated factor 1 [KO:K03172]
118237153  pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
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
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Related
pathway
aang04010  MAPK signaling pathway
aang04020  Calcium signaling pathway
aang04115  p53 signaling pathway
aang04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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