KEGG   PATHWAY: bom04210
Entry
bom04210                    Pathway                                
Name
Apoptosis - Bos mutus (wild yak)
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
bom04210  Apoptosis
bom04210

Other DBs
GO: 0006915
Organism
Bos mutus (wild yak) [GN:bom]
Gene
102264327  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102264458  DAXX; LOW QUALITY PROTEIN: death domain-associated protein 6 [KO:K02308]
102264869  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
102264909  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
102265427  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102265582  CTSZ; LOW QUALITY PROTEIN: cathepsin Z [KO:K08568] [EC:3.4.18.1]
102266544  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102266922  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102266960  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102266978  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102267423  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102267895  JUN; transcription factor Jun [KO:K04448]
102268339  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
102268417  RELA; transcription factor p65 [KO:K04735]
102268592  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
102268660  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
102269013  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform X1 [KO:K04959]
102269088  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform X1 [KO:K04958]
102269203  NRAS; GTPase NRas [KO:K07828]
102269419  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
102269473  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
102269764  PRF1; perforin-1 [KO:K07818]
102269806  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
102269928  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
102270684  TUBA1B; tubulin alpha-1B chain [KO:K07374]
102270759  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
102270765  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
102271039  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 [KO:K04960]
102271103  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
102271108  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
102271380  [KO:K04570]
102271384  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
102271614  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
102271710  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X2 [KO:K04369] [EC:2.7.12.2]
102271835  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
102271962  FADD; FAS-associated death domain protein [KO:K02373]
102272318  DIABLO; diablo IAP-binding mitochondrial protein [KO:K10522]
102272368  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102272370  TP53; cellular tumor antigen p53 [KO:K04451]
102272421  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102272462  NOL3; nucleolar protein 3 isoform X1 [KO:K28177]
102272602  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
102272716  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
102272786  CASP2; LOW QUALITY PROTEIN: caspase-2 [KO:K02186] [EC:3.4.22.55]
102272990  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070]
102273045  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
102273081  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
102273906  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
102274461  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102274553  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102275014  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
102275053  FOS; protein c-Fos [KO:K04379]
102275096  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
102275172  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
102275265  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102275402  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102275570  ENDOG; endonuclease G, mitochondrial [KO:K01173]
102275669  PARP4; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
102275760  IL3; interleukin-3 [KO:K04736]
102275829  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102275975  BAD; bcl2-associated agonist of cell death [KO:K02158]
102276116  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102276156  BCL2L11; LOW QUALITY PROTEIN: bcl-2-like protein 11 [KO:K16341]
102276298  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
102276829  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
102276849  MAP3K5; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
102276866  [KO:K08738]
102277011  HRAS; GTPase HRas isoform X1 [KO:K02833]
102277355  BCL2L1; bcl-2-like protein 1 [KO:K04570]
102277548  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102277620  CYCS; cytochrome c [KO:K08738]
102277911  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102277976  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102278591  [KO:K02833]
102278968  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102279029  LMNB2; lamin-B2 [KO:K07611]
102279560  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
102279740  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
102279783  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102279846  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
102279969  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
102280081  BCL2A1; bcl-2-related protein A1 [KO:K02162]
102280120  TUBA8; tubulin alpha-8 chain [KO:K07374]
102280130  PARP3; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.-]
102280217  LMNA; LOW QUALITY PROTEIN: lamin [KO:K12641]
102280296  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
102280670  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102280742  [KO:K07374]
102281142  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
102281208  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
102281213  [KO:K07374]
102281443  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102281886  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102281889  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102281958  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
102282130  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
102282298  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
102283099  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
102283212  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102283384  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
102283393  [KO:K08738]
102283650  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
102284902  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
102284921  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
102284931  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102285097  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
102285196  [KO:K01353] [EC:3.4.21.79]
102285398  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
102285463  [KO:K01353] [EC:3.4.21.79]
102285564  ACTG1; actin, cytoplasmic 2 [KO:K05692]
102285660  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
102285873  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102286048  ACTB; LOW QUALITY PROTEIN: actin, cytoplasmic 1 [KO:K05692]
102286144  LMNB1; lamin-B1 [KO:K07611]
102286500  KRAS; GTPase KRas isoform X1 [KO:K07827]
102286771  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
102286868  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102286892  [KO:K01353] [EC:3.4.21.79]
102286969  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102287110  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
102287237  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
102287348  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
102287477  NGF; LOW QUALITY PROTEIN: beta-nerve growth factor [KO:K02582]
102287586  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
102287626  SEPTIN4; septin-4 isoform X2 [KO:K16943]
102287709  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102287968  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102288000  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102288095  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
102288216  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106700494  [KO:K08738]
138983909  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
138984377  [KO:K01353] [EC:3.4.21.79]
138987704  [KO:K07374]
138987928  [KO:K07374]
138991436  HRK; activator of apoptosis harakiri [KO:K02512]
138991458  [KO:K07374]
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
bom04010  MAPK signaling pathway
bom04020  Calcium signaling pathway
bom04064  NF-kappa B signaling pathway
bom04115  p53 signaling pathway
bom04141  Protein processing in endoplasmic reticulum
bom04151  PI3K-Akt signaling pathway
bom04650  Natural killer cell mediated cytotoxicity
bom04668  TNF signaling pathway
KO pathway
ko04210   

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