KEGG   PATHWAY: bbis04210
Entry
bbis04210                   Pathway                                
Name
Apoptosis - Bison bison bison (American bison)
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
bbis04210  Apoptosis
bbis04210

Other DBs
GO: 0006915
Organism
Bison bison bison (American bison) [GN:bbis]
Gene
104979900  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104980006  HRK; activator of apoptosis harakiri [KO:K02512]
104980781  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
104980877  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
104980990  [KO:K04570]
104981526  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981573  NGF; beta-nerve growth factor [KO:K02582]
104981582  NRAS; GTPase NRas [KO:K07828]
104982240  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
104982944  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104982962  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
104983770  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104984118  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
104984139  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
104984204  [KO:K04722]
104984335  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
104984424  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
104984445  [KO:K04725] [EC:2.3.2.27]
104984678  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
104984835  [KO:K07374]
104984854  [KO:K07374]
104984863  [KO:K16060]
104985206  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
104985237  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104985538  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
104985708  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
104985727  [KO:K01365] [EC:3.4.22.15]
104986157  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
104986245  [KO:K04456] [EC:2.7.11.1]
104986748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104986928  FADD; LOW QUALITY PROTEIN: FAS-associated death domain protein [KO:K02373]
104986991  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
104987020  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
104987029  RELA; transcription factor p65 [KO:K04735]
104987190  BAD; LOW QUALITY PROTEIN: bcl2-associated agonist of cell death [KO:K02158]
104987221  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
104987347  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
104987378  LMNA; LOW QUALITY PROTEIN: lamin [KO:K12641]
104987521  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
104987657  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
104987659  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
104987708  MCL1; LOW QUALITY PROTEIN: induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
104988119  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
104988226  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
104988504  [KO:K08738]
104988812  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
104988870  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
104989603  DIABLO; diablo homolog, mitochondrial [KO:K10522]
104989637  [KO:K04456] [EC:2.7.11.1]
104989915  BCL2L1; bcl-2-like protein 1 [KO:K04570]
104989978  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
104990761  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
104990903  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
104990909  [KO:K02162]
104991008  [KO:K01353] [EC:3.4.21.79]
104991009  [KO:K01353] [EC:3.4.21.79]
104991014  [KO:K01353] [EC:3.4.21.79]
104991016  [KO:K01353] [EC:3.4.21.79]
104991056  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
104991589  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
104991715  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
104992057  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104992248  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
104992258  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
104992261  TUBA8; tubulin alpha-8 chain [KO:K07374]
104992338  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
104992716  [KO:K02649]
104992781  ACTB; actin, cytoplasmic 1 [KO:K05692]
104992939  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104993201  LMNB1; lamin-B1 [KO:K07611]
104993223  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
104993381  TUBA3E; tubulin alpha-3E chain [KO:K07374]
104993460  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
104993805  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
104994333  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
104994580  [KO:K04722]
104994637  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
104994750  [KO:K07374]
104994766  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
104994906  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
104994997  DAXX; death domain-associated protein 6 [KO:K02308]
104995001  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104995356  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104995620  [KO:K04371] [EC:2.7.11.24]
104995631  BAX; apoptosis regulator BAX [KO:K02159]
104995820  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104995851  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
104995905  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
104995965  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
104996058  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104996168  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
104996714  NOL3; nucleolar protein 3 [KO:K28177]
104996716  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
104996847  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.-]
104997276  PARP3; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.-]
104997388  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
104997473  PRF1; perforin-1 [KO:K07818]
104997639  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
104997797  BBC3; bcl-2-binding component 3 [KO:K10132]
104997873  [KO:K03853] [EC:3.4.22.53]
104997899  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070]
104998445  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104998531  [KO:K07374]
104998999  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104999231  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
104999240  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
104999778  [KO:K08738]
104999978  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105000057  FOS; proto-oncogene c-Fos [KO:K04379]
105000175  JUN; transcription factor AP-1 [KO:K04448]
105000225  KRAS; GTPase KRas isoform X1 [KO:K07827]
105000232  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105000397  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
105000428  ACTG1; LOW QUALITY PROTEIN: actin, cytoplasmic 2 [KO:K05692]
105000492  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
105000813  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
105000896  ENDOG; endonuclease G, mitochondrial [KO:K01173]
105001321  [KO:K02861] [EC:2.7.11.1]
105001471  TUBA1B; tubulin alpha-1B chain [KO:K07374]
105001472  TUBA1A; tubulin alpha-1A chain [KO:K07374]
105001799  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105002081  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
105002606  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
105002719  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105002922  [KO:K08738]
105003408  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
105003597  [KO:K04456] [EC:2.7.11.1]
105003652  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
105003655  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105003692  HRAS; GTPase HRas [KO:K02833]
105003795  [KO:K07374]
105003796  [KO:K07374]
105004101  SEPT4; septin-4 isoform X1 [KO:K16943]
105004742  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
105005011  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
105005553  [KO:K04736]
105005582  LMNB2; lamin-B2 [KO:K07611]
105005583  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
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
bbis04010  MAPK signaling pathway
bbis04020  Calcium signaling pathway
bbis04064  NF-kappa B signaling pathway
bbis04115  p53 signaling pathway
bbis04141  Protein processing in endoplasmic reticulum
bbis04151  PI3K-Akt signaling pathway
bbis04650  Natural killer cell mediated cytotoxicity
bbis04668  TNF signaling pathway
KO pathway
ko04210   

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