KEGG   PATHWAY: btax04210
Entry
btax04210                   Pathway                                
Name
Apoptosis - Budorcas taxicolor (takin)
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
btax04210  Apoptosis
btax04210

Other DBs
GO: 0006915
Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128055119  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
128052079  tumor necrosis factor receptor superfamily member 10C-like [KO:K04722]
128052097  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
128052227  tumor necrosis factor receptor superfamily member 10C-like isoform X1 [KO:K04722]
128061812  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
128067871  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
128068641  FADD; FAS-associated death domain protein [KO:K02373]
128056772  TNF; tumor necrosis factor [KO:K03156]
128047668  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
128063092  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
128066790  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
128064775  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
128060900  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
128049865  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
128068336  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
128067718  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
128047923  BID; BH3-interacting domain death agonist [KO:K04726]
128064207  BAX; apoptosis regulator BAX [KO:K02159]
128056082  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
128062295  DIABLO; diablo IAP-binding mitochondrial protein [KO:K10522]
128064377  septin-4 isoform X1 [KO:K16943]
128055221  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
128069489  cytochrome c 2 [KO:K08738]
128046227  cytochrome c [KO:K08738]
128053843  cytochrome c-like [KO:K08738]
128053924  cytochrome c [KO:K08738]
128054019  cytochrome c-like [KO:K08738]
128048021  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
128061241  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
128048835  PRF1; perforin-1 [KO:K07818]
128066475  mast cell protease 1A [KO:K01353] [EC:3.4.21.79]
128066549  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
128066641  mast cell protease 3 [KO:K01353] [EC:3.4.21.79]
128066644  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
128067007  granzyme B-like [KO:K01353] [EC:3.4.21.79]
128067008  granzyme B-like [KO:K01353] [EC:3.4.21.79]
128063978  TUBA4A; tubulin alpha-4A chain isoform X1 [KO:K07374]
128058048  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
128047715  TUBA8; tubulin alpha-8 chain [KO:K07374]
128068330  tubulin alpha-1D chain [KO:K07374]
128048810  tubulin alpha-1C chain isoform X1 [KO:K07374]
128048811  tubulin alpha-1C chain-like [KO:K07374]
128048812  tubulin alpha-1B chain [KO:K07374]
128048813  tubulin alpha-1A chain isoform X1 [KO:K07374]
128062492  tubulin alpha-3 chain [KO:K07374]
128062504  tubulin alpha-3 chain-like [KO:K07374]
128045164  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
128043956  ACTB; actin, cytoplasmic 1 [KO:K05692]
128064385  ACTG1; actin, cytoplasmic 2 [KO:K05692]
128055954  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
128044385  LMNA; lamin [KO:K12641]
128050441  LMNB1; lamin-B1 [KO:K07611]
128050585  LMNB2; lamin-B2 [KO:K07611]
128066551  poly [ADP-ribose] polymerase 1-like [KO:K24070] [EC:2.4.2.30]
128061402  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
128057524  PARP4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.30]
128070557  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
128054289  PARP2; poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
128067485  poly [ADP-ribose] polymerase 2-like [KO:K10798] [EC:2.4.2.30]
128061633  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
128061584  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
128056575  ENDOG; endonuclease G, mitochondrial [KO:K01173]
128069798  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
128064658  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
128055475  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
128046429  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
128048527  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
128056281  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
128069183  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
128061180  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
128056196  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
128054117  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
128047885  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
128048350  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
128047285  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
128052199  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
128068741  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
128068646  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
128068661  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
128066659  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
128044625  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
128052286  procathepsin L [KO:K01365] [EC:3.4.22.15]
128052428  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
128062600  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
128044918  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
128068966  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
128058117  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
128060118  BIRC2; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2 [KO:K16060]
128060491  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
128070186  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
128065504  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
128055401  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
128058470  BCL2L1; bcl-2-like protein 1 [KO:K04570]
128059210  LOW QUALITY PROTEIN: bcl-2-like protein 1 [KO:K04570]
128067358  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
128055526  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
128055992  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
128055230  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
128053214  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
128051495  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
128047244  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128049619  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
128068977  BAD; bcl2-associated agonist of cell death [KO:K02158]
128044447  JUN; transcription factor Jun [KO:K04448]
128053951  FOS; protein c-Fos [KO:K04379]
128049822  LOW QUALITY PROTEIN: cellular tumor antigen p53-like [KO:K04451]
128064672  TP53; cellular tumor antigen p53 [KO:K04451]
128062659  HRK; activator of apoptosis harakiri [KO:K02512]
128065013  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
128067677  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
128068238  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
128069947  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
128066643  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
128049417  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
128068546  RELA; transcription factor p65 [KO:K04735]
128049453  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
128050874  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
128044871  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
128052323  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
128052448  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
128066960  BCL2A1; bcl-2-related protein A1 [KO:K02162]
128060504  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
128068943  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
128064189  BBC3; bcl-2-binding component 3 [KO:K10132]
128067549  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
128046509  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
128045179  NGF; beta-nerve growth factor [KO:K02582]
128044483  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
128051755  interleukin-3 [KO:K04736]
128070407  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
128047746  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
128045803  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128061813  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128068699  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128050540  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128044474  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
128066235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
128060129  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
128063870  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128067048  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061491  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128068689  HRAS; GTPase HRas isoform X1 [KO:K02833]
128047937  KRAS; GTPase KRas [KO:K07827]
128044537  NRAS; GTPase NRas [KO:K07828]
128043403  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128054045  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128050664  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128062160  MAPK1; mitogen-activated protein kinase 1 [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
btax04010  MAPK signaling pathway
btax04020  Calcium signaling pathway
btax04064  NF-kappa B signaling pathway
btax04115  p53 signaling pathway
btax04141  Protein processing in endoplasmic reticulum
btax04151  PI3K-Akt signaling pathway
btax04650  Natural killer cell mediated cytotoxicity
btax04668  TNF signaling pathway
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system