KEGG   PATHWAY: bbuf04210
Entry
bbuf04210                   Pathway                                
Name
Apoptosis - Bufo bufo (common toad)
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
bbuf04210  Apoptosis
bbuf04210

Other DBs
GO: 0006915
Organism
Bufo bufo (common toad) [GN:bbuf]
Gene
120977045  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
120977084  ENDOG; endonuclease G, mitochondrial [KO:K01173]
120977195  [KO:K04725] [EC:2.3.2.27]
120977198  [KO:K03853] [EC:3.4.22.53]
120977315  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
120977834  [KO:K03156]
120977869  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
120977943  [KO:K07374]
120978007  [KO:K19901]
120978563  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
120978575  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
120978631  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.-]
120978688  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
120978714  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
120978943  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
120979042  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
120979333  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
120979744  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
120979831  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
120980123  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
120980177  FADD; FAS-associated death domain protein [KO:K02373]
120980391  RELA; transcription factor p65 isoform X1 [KO:K04735]
120980824  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
120980825  [KO:K01367] [EC:3.4.22.52]
120981003  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
120981053  HRAS; GTPase HRas isoform X1 [KO:K02833]
120981110  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
120981127  [KO:K01379] [EC:3.4.23.5]
120981141  [KO:K04722]
120981181  [KO:K01379] [EC:3.4.23.5]
120981563  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
120981700  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
120981857  [KO:K01371] [EC:3.4.22.38]
120982069  [KO:K01371] [EC:3.4.22.38]
120982070  [KO:K01368] [EC:3.4.22.27]
120982209  FOS; proto-oncogene c-Fos [KO:K04379]
120982316  BAD; bcl2-associated agonist of cell death [KO:K02158]
120982346  LMNA; lamin [KO:K12641]
120982425  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
120982478  [KO:K01368] [EC:3.4.22.27]
120982515  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
120982548  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120984531  [KO:K07374]
120984547  [KO:K07374]
120985711  [KO:K01365] [EC:3.4.22.15]
120985714  [KO:K01365] [EC:3.4.22.15]
120985715  [KO:K01365] [EC:3.4.22.15]
120985868  [KO:K07611]
120986019  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120986314  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
120986731  [KO:K04451]
120987211  [KO:K04397] [EC:3.4.22.60]
120988482  LMNB1; lamin-B1 isoform X1 [KO:K07611]
120988593  DIABLO; diablo homolog, mitochondrial [KO:K10522]
120988704  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120988950  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
120989077  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
120989104  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
120989541  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
120989607  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120989612  LMNB2; lamin-B2 [KO:K07611]
120989710  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
120989857  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
120989915  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
120990143  [KO:K02187] [EC:3.4.22.56]
120990145  [KO:K02187] [EC:3.4.22.56]
120990444  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
120990589  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
120991615  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
120991666  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120991680  [KO:K07374]
120991742  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
120992235  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
120992399  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120993269  [KO:K16943]
120993328  NGF; beta-nerve growth factor [KO:K02582]
120993933  [KO:K08731]
120993957  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
120994003  PARP4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
120994996  NRAS; GTPase NRas isoform X1 [KO:K07828]
120995158  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
120995161  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
120995176  [KO:K07374]
120995963  [KO:K07374]
120995966  [KO:K07374]
120995967  [KO:K07374]
120996062  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
120996370  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
120996399  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
120996451  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
120996957  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
120997204  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
120997646  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120997891  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
120997902  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120998524  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
120998617  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
120998695  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
120999612  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
120999625  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
120999697  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
120999823  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
121001044  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
121001072  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
121001799  [KO:K07827]
121002252  [KO:K08738]
121002334  BAX; apoptosis regulator BAX [KO:K02159]
121003202  ACTG1; actin, cytoplasmic 2 [KO:K05692]
121003247  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
121003342  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
121003720  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
121003741  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
121003754  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
121004043  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
121004181  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
121004207  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
121004327  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
121004595  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
121004701  TUBA8; tubulin alpha-8 chain [KO:K07374]
121004973  KRAS; GTPase KRas isoform X1 [KO:K07827]
121005536  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
121005917  BCL2L1; bcl-2-like protein 1 [KO:K04570]
121007440  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
121007625  [KO:K04400] [EC:3.4.22.63]
121008002  [KO:K07818]
121008062  [KO:K07818]
121008219  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
121008461  [KO:K04398] [EC:3.4.22.61]
121008493  [KO:K05692]
121008571  [KO:K07818]
121008588  [KO:K08738]
121008856  [KO:K07374]
121008860  [KO:K07374]
121008861  [KO:K07374]
121008862  [KO:K07374]
121008868  [KO:K07374]
121008981  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
121009140  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
121009286  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121009326  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
121009330  [KO:K01367] [EC:3.4.22.52]
121009474  DAXX; death domain-associated protein 6 [KO:K02308]
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
bbuf04010  MAPK signaling pathway
bbuf04020  Calcium signaling pathway
bbuf04115  p53 signaling pathway
bbuf04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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