KEGG   PATHWAY: lcm04210
Entry
lcm04210                    Pathway                                
Name
Apoptosis - Latimeria chalumnae (coelacanth)
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
lcm04210  Apoptosis
lcm04210

Other DBs
GO: 0006915
Organism
Latimeria chalumnae (coelacanth) [GN:lcm]
Gene
102345421  TNFSF10; tumor necrosis factor superfamily member 10 [KO:K04721]
102366259  uncharacterized LOC102366259 [KO:K04722]
102366681  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
102361530  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
102366280  FASLG; Fas ligand [KO:K04389]
102361141  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
102349412  FAS; Fas cell surface death receptor [KO:K04390]
102357786  FADD; Fas associated via death domain [KO:K02373]
102357196  TNF; tumor necrosis factor [KO:K03156]
102356355  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102365247  TRADD; TNFRSF1A associated via death domain [KO:K03171]
102359774  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
102355925  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102356202  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102349989  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102356934  CASP6; caspase 6 [KO:K04396] [EC:3.4.22.59]
106705928  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
102367521  caspase-3-like [KO:K04397] [EC:3.4.22.60]
102357990  CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
102360597  BID; BH3-interacting domain death agonist [KO:K04726]
102359041  apoptosis regulator BAX-like [KO:K02159]
102352490  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102364872  bcl-2 homologous antagonist/killer-like [KO:K14021]
102345216  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
102361759  DIABLO; diablo IAP-binding mitochondrial protein [KO:K10522]
102345982  SEPT4; septin 4 [KO:K16943]
102353741  uncharacterized LOC102353741 [KO:K16943]
102365454  septin-4-like [KO:K16943]
102356234  HTRA2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
102363280  cytochrome c [KO:K08738]
102345199  cytochrome c-like [KO:K08738]
102354670  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
102362720  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
102349263  perforin-1-like [KO:K07818]
102350216  PRF1; perforin 1 [KO:K07818]
102356836  perforin-1-like [KO:K07818]
102365546  perforin-1-like [KO:K07818]
102365978  perforin-1-like [KO:K07818]
102367099  tubulin alpha-8 chain [KO:K07374]
102345879  TUBA1C; tubulin alpha-1C chain [KO:K07374]
102347030  tubulin alpha-1B chain-like [KO:K07374]
102347472  tubulin alpha-1B chain [KO:K07374]
102362449  TUBA8; tubulin alpha-8 chain [KO:K07374]
102346946  tubulin alpha-1A chain-like [KO:K07374]
102347483  tubulin alpha chain [KO:K07374]
102345731  tubulin alpha-8 chain-like [KO:K07374]
102345654  tubulin alpha-1 chain-like [KO:K07374]
102350724  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
102366223  actin, cytoplasmic type 5-like [KO:K05692]
102362654  ACTB; actin beta [KO:K05692]
102366472  actin, cytoplasmic type 5 [KO:K05692]
102352163  ACTRT3; actin related protein T3 [KO:K05692]
102367477  SPTAN1; spectrin alpha, non-erythrocytic 1 [KO:K06114]
102359604  LMNA; lamin A/C [KO:K12641]
102347052  lamin-L(III)-like [KO:K07611]
102361059  LMNB2; lamin B2 [KO:K07611]
102360421  LMNB1; lamin B1 [KO:K07611]
102348307  PARP1; poly(ADP-ribose) polymerase 1 [KO:K24070] [EC:2.4.2.30]
102367087  PARP3; poly(ADP-ribose) polymerase family member 3 [KO:K10798] [EC:2.4.2.30]
102359086  PARP4; poly(ADP-ribose) polymerase family member 4 [KO:K10798] [EC:2.4.2.30]
102361584  PARP2; poly(ADP-ribose) polymerase 2 [KO:K10798] [EC:2.4.2.30]
102363225  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
102365867  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
102347242  ENDOG; endonuclease G [KO:K01173]
102361781  AIFM1; apoptosis inducing factor mitochondria associated 1 [KO:K04727] [EC:1.-.-.-]
102363303  ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
102352244  ERN2; endoplasmic reticulum to nucleus signaling 2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
102360751  TNF receptor-associated factor 1-like [KO:K03173] [EC:2.3.2.27]
102355783  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
102358173  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
102361301  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102359880  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102349825  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102347136  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
102363773  CAPN11; calpain 11 [KO:K01367] [EC:3.4.22.52]
102347065  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
102367658  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
102365086  ATF4; activating transcription factor 4 [KO:K04374]
102361121  DDIT3; DNA damage inducible transcript 3 [KO:K04452]
102351271  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
102365650  CTSC; cathepsin C [KO:K01275] [EC:3.4.14.1]
102355307  cathepsin D-like [KO:K01379] [EC:3.4.23.5]
102351433  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102362412  CTSW; cathepsin W [KO:K01373] [EC:3.4.22.41]
102345521  cathepsin F-like [KO:K01373] [EC:3.4.22.41]
102358878  CTSH; cathepsin H [KO:K01366] [EC:3.4.22.16]
102352136  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102360396  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
102358477  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
102351388  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
102346436  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
102351684  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
102365039  cathepsin S-like [KO:K01368] [EC:3.4.22.27]
102354050  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
102364182  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
102349446  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
102348297  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
102346472  baculoviral IAP repeat-containing protein 5.1-like [KO:K08731]
102358181  BCL2L1; BCL2 like 1 [KO:K04570]
102349300  DAXX; death domain associated protein [KO:K02308]
102363596  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
102348363  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
102352283  MAP3K6; mitogen-activated protein kinase kinase kinase 6 [KO:K04426] [EC:2.7.11.25]
102357573  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102351693  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102351958  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102363793  BAD; BCL2 associated agonist of cell death [KO:K02158]
102350279  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102358101  transcription factor AP-1-like [KO:K04448]
102361375  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102366539  TP53; tumor protein p53 [KO:K04451]
102351315  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102361819  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102358966  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102351908  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102347685  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102356725  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102352496  PTPN13; protein tyrosine phosphatase, non-receptor type 13 [KO:K02374]
102353479  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102361538  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102349018  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102352896  TNF receptor-associated factor 1-like [KO:K03172]
102347668  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
102349614  PIDD1; p53-induced death domain protein 1 [KO:K10130]
102349624  CASP2; caspase 2 [KO:K02186] [EC:3.4.22.55]
102364322  NGF; nerve growth factor [KO:K02582]
102354132  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
102352551  cytokine receptor common subunit beta-like [KO:K04738]
102351622  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102350948  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102351332  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
102359335  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102353218  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102348007  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102346160  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102359797  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102359272  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102346546  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102355427  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102352473  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102357700  GTPase HRas-like [KO:K07827]
102361045  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102357545  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102358560  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102350370  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102355992  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102354262  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
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
Related
pathway
lcm04010  MAPK signaling pathway
lcm04020  Calcium signaling pathway
lcm04115  p53 signaling pathway
lcm04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   
LinkDB

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