KEGG   PATHWAY: acs04210
Entry
acs04210                    Pathway                                
Name
Apoptosis - Anolis carolinensis (green anole)
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
acs04210  Apoptosis
acs04210

Other DBs
GO: 0006915
Organism
Anolis carolinensis (green anole) [GN:acs]
Gene
100337533  actb; actin beta [KO:K05692]
100551616  map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
100551680  eif2ak3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
100551688  fas; Fas cell surface death receptor [KO:K04390]
100551699  ikbkb; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100551715  [KO:K01367] [EC:3.4.22.52]
100552506  lmnb1; lamin B1 [KO:K07611]
100552908  parp3; poly(ADP-ribose) polymerase family member 3 [KO:K10798] [EC:2.4.2.-]
100553155  lmna; lamin A/C [KO:K12641]
100553353  [KO:K03172]
100553574  ngf; nerve growth factor [KO:K02582]
100553927  akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
100554030  birc2; baculoviral IAP repeat containing 2 [KO:K16060]
100554443  gadd45a; growth arrest and DNA damage inducible alpha [KO:K04402]
100554618  pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
100554621  tuba8; tubulin alpha-8 chain [KO:K07374]
100554664  nfkbia; NFKB inhibitor alpha [KO:K04734]
100554702  faslg; Fas ligand [KO:K04389]
100554765  eif2s1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
100554975  dffb; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
100555021  [KO:K07818]
100555182  pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
100555477  akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100555877  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100556163  rela; RELA proto-oncogene, NF-kB subunit [KO:K04735]
100556206  ripk1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
100556289  akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
100556318  apaf1; apoptotic peptidase activating factor 1 [KO:K02084]
100556341  [KO:K03158]
100556408  [KO:K04728] [EC:2.7.11.1]
100556427  fos; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
100556611  ntrk1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
100556744  mcl1; BCL2 family apoptosis regulator [KO:K02539]
100556836  tradd; TNFRSF1A associated via death domain [KO:K03171]
100556883  pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
100557613  raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100557644  xiap; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
100558211  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100558581  ern2; endoplasmic reticulum to nucleus signaling 2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
100558982  [KO:K04368] [EC:2.7.12.2]
100559158  [KO:K08568] [EC:3.4.18.1]
100559357  [KO:K08568] [EC:3.4.18.1]
100559555  [KO:K08568] [EC:3.4.18.1]
100559751  [KO:K08568] [EC:3.4.18.1]
100559769  [KO:K04722]
100559807  [KO:K07827]
100559887  [KO:K08738]
100559955  pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100560015  capn1; calpain 1 [KO:K01367] [EC:3.4.22.52]
100560063  atm; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
100560103  casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
100560190  map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100560604  tubal3; tubulin alpha like 3 [KO:K07374]
100560655  [KO:K08738]
100560943  ctss; cathepsin S [KO:K01368] [EC:3.4.22.27]
100561101  [KO:K03156]
100561141  traf2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
100561212  [KO:K07374]
100561388  [KO:K08731]
100561542  [KO:K07374]
100561594  dffa; DNA fragmentation factor subunit alpha [KO:K02310]
100561600  ctsh; cathepsin H [KO:K01366] [EC:3.4.22.16]
100561728  ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
100561730  [KO:K16943]
100561808  capn2; calpain 2 [KO:K03853] [EC:3.4.22.53]
100561907  mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100561911  [KO:K02159]
100561922  bcl2l1; BCL2 like 1 [KO:K04570]
100561941  ctsl; cathepsin L [KO:K01365] [EC:3.4.22.15]
100562036  [KO:K07374]
100562152  tuba1c; tubulin alpha-8 chain [KO:K07374]
100562235  [KO:K07374]
100562345  pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
100562576  aifm1; apoptosis inducing factor mitochondria associated 1 [KO:K04727] [EC:1.-.-.-]
100562623  ctso; cathepsin O [KO:K01374] [EC:3.4.22.42]
100562834  bax; apoptosis regulator BAX [KO:K02159]
100563259  [KO:K07374]
100563335  parp4; poly(ADP-ribose) polymerase family member 4 [KO:K10798] [EC:2.4.2.-]
100563575  kras; KRAS proto-oncogene, GTPase [KO:K07827]
100563621  [KO:K01379] [EC:3.4.23.5]
100563813  casp7; caspase 7 [KO:K04397] [EC:3.4.22.60]
100563878  ctsb; cathepsin B [KO:K01363] [EC:3.4.22.1]
100563896  [KO:K01365] [EC:3.4.22.15]
100563931  casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
100563997  bid; BH3 interacting domain death agonist [KO:K04726]
100564002  casp6; caspase 6 [KO:K04396] [EC:3.4.22.59]
100564281  casp10; caspase 10 [KO:K04400] [EC:3.4.22.63]
100564288  [KO:K08568] [EC:3.4.18.1]
100564298  pidd1; p53-induced death domain protein 1 [KO:K10130]
100564373  actg1; actin gamma 1 [KO:K05692]
100564389  [KO:K07374]
100564450  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100564476  cflar; CASP8 and FADD like apoptosis regulator [KO:K04724]
100564650  bak1; BCL2 antagonist/killer 1 [KO:K14021]
100564886  bcl2; apoptosis regulator Bcl-2 [KO:K02161]
100565020  [KO:K06114]
100565042  ctsc; cathepsin C [KO:K01275] [EC:3.4.14.1]
100565079  htra2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
100565176  nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100565177  atf4; activating transcription factor 4 [KO:K04374]
100565678  hras; HRas proto-oncogene, GTPase [KO:K02833]
100565814  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100565922  chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100566215  birc5; baculoviral IAP repeat containing 5 [KO:K08731]
100566271  dab2ip; DAB2 interacting protein [KO:K19901]
100566501  parp2; poly(ADP-ribose) polymerase 2 [KO:K28005]
100566541  tnfsf10; tumor necrosis factor superfamily member 10 [KO:K04721]
100566579  diablo; diablo IAP-binding mitochondrial protein [KO:K10522]
100566699  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100566747  ptpn13; protein tyrosine phosphatase, non-receptor type 13 [KO:K02374]
100566768  ern1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
100566904  [KO:K03173] [EC:2.3.2.27]
100567116  [KO:K01367] [EC:3.4.22.52]
100567119  ikbkg; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100567176  map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100567238  ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
100567254  pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100567364  [KO:K00922] [EC:2.7.1.153]
100567376  parp1; poly(ADP-ribose) polymerase 1 [KO:K24070]
100567470  ddit3; DNA damage inducible transcript 3 [KO:K04452]
100567488  [KO:K05692]
100567718  jun; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
100567806  casp2; caspase 2 [KO:K02186] [EC:3.4.22.55]
100567812  gadd45g; growth arrest and DNA damage inducible gamma [KO:K04402]
100567848  [KO:K07374]
100567982  itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100568038  itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100568076  [KO:K05692]
100568252  pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103278072  [KO:K03156]
103278847  csf2rb; colony stimulating factor 2 receptor beta common subunit [KO:K04738]
103279556  [KO:K07818]
103279978  fadd; Fas associated via death domain [KO:K02373]
103280258  pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
103281217  tnfrsf10b; TNF receptor superfamily member 10b [KO:K04722]
103281402  [KO:K08568] [EC:3.4.18.1]
103282543  [KO:K04451]
103283025  [KO:K01373] [EC:3.4.22.41]
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
acs04010  MAPK signaling pathway
acs04020  Calcium signaling pathway
acs04115  p53 signaling pathway
acs04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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