KEGG   PATHWAY: tup04210
Entry
tup04210                    Pathway                                
Name
Apoptosis - Tupaia chinensis (Chinese tree shrew)
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
tup04210  Apoptosis
tup04210

Other DBs
GO: 0006915
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102467954  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102468404  LMNB1; lamin B1 [KO:K07611]
102468736  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
102468854  [KO:K08738]
102469152  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102469586  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
102469595  PARP3; poly(ADP-ribose) polymerase family member 3 [KO:K10798] [EC:2.4.2.-]
102470650  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
102470651  [KO:K07374]
102470940  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
102470949  CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
102471776  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102472210  [KO:K01353] [EC:3.4.21.79]
102472233  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102472298  SEPT4; septin 4 [KO:K16943]
102472374  PARP2; poly(ADP-ribose) polymerase 2 [KO:K28005]
102472561  MCL1; BCL2 family apoptosis regulator [KO:K02539]
102472926  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
102473071  [KO:K01353] [EC:3.4.21.79]
102473622  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102473925  C8G; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102474582  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102474592  BCL2; BCL2, apoptosis regulator [KO:K02161]
102475532  [KO:K01365] [EC:3.4.22.15]
102475587  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102475730  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102476020  IL3RA; interleukin 3 receptor subunit alpha [KO:K04737]
102476101  LMNB2; lamin B2 [KO:K07611]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102476523  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102476587  FAS; Fas cell surface death receptor [KO:K04390]
102476690  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
102476758  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102476798  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
102477463  ENDOG; endonuclease G [KO:K01173]
102477797  BID; BH3 interacting domain death agonist [KO:K04726]
102478154  ATF4; activating transcription factor 4 [KO:K04374]
102478636  TRADD; TNFRSF1A associated via death domain [KO:K03171]
102479545  [KO:K08738]
102479844  DAB2IP; DAB2 interacting protein [KO:K19901]
102479926  ACTB; actin beta [KO:K05692]
102480161  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
102480185  TUBAL3; tubulin alpha like 3 [KO:K07374]
102480372  PARP4; poly(ADP-ribose) polymerase family member 4 [KO:K10798] [EC:2.4.2.-]
102481062  DAXX; death domain associated protein [KO:K02308]
102481080  CASP6; caspase 6 [KO:K04396] [EC:3.4.22.59]
102481316  CAPN2; calpain 2 [KO:K03853] [EC:3.4.22.53]
102481330  TUBA8; tubulin alpha 8 [KO:K07374]
102482353  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
102482492  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
102482790  PIDD1; p53-induced death domain protein 1 [KO:K10130]
102482868  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102483590  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
102483700  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102483972  CTSH; cathepsin H [KO:K01366] [EC:3.4.22.16]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484458  DIABLO; diablo IAP-binding mitochondrial protein [KO:K10522]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102485200  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
102485234  BCL2A1; BCL2 related protein A1 [KO:K02162]
102486626  BCL2L1; BCL2 like 1 [KO:K04570]
102487119  [KO:K02187] [EC:3.4.22.56]
102487370  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
102487413  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102488201  CTSC; cathepsin C [KO:K01275] [EC:3.4.14.1]
102489149  [KO:K04722]
102489486  [KO:K04741] [EC:3.4.22.-]
102489799  FADD; Fas associated via death domain [KO:K02373]
102490430  [KO:K01365] [EC:3.4.22.15]
102490451  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102491111  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
102491199  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102491255  [KO:K01365] [EC:3.4.22.15]
102491528  [KO:K01353] [EC:3.4.21.79]
102491775  PARP1; poly(ADP-ribose) polymerase 1 [KO:K24070]
102491971  ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
102492330  [KO:K07374]
102492596  LMNA; lamin A/C [KO:K12641]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102492779  [KO:K01353] [EC:3.4.21.79]
102492983  [KO:K08738]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102493692  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
102493795  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
102493987  TRAF1; TNF receptor associated factor 1 [KO:K03172]
102494213  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
102494501  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
102494635  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102494910  TUBA1C; tubulin alpha-1C chain [KO:K07374]
102495244  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
102495248  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
102495380  PTPN13; protein tyrosine phosphatase, non-receptor type 13 [KO:K02374]
102496008  TUBA4A; tubulin alpha-4A chain [KO:K07374]
102496191  [KO:K08738]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102496563  CASP10; caspase 10 [KO:K04400] [EC:3.4.22.63]
102496694  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
102496850  [KO:K07374]
102496861  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102496870  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102497095  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102497162  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
102497170  [KO:K04722]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102497633  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102497973  TNF; tumor necrosis factor [KO:K03156]
102498069  BAD; BCL2 associated agonist of cell death [KO:K02158]
102498355  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
102498431  ACTG1; actin gamma 1 [KO:K05692]
102498970  CASP2; caspase 2 [KO:K02186] [EC:3.4.22.55]
102499950  BBC3; BCL2 binding component 3 [KO:K10132]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102500161  AIFM1; apoptosis inducing factor mitochondria associated 1 [KO:K04727] [EC:1.-.-.-]
102500216  DDIT3; DNA damage inducible transcript 3 [KO:K04452]
102500340  CSF2RB; colony stimulating factor 2 receptor beta common subunit [KO:K04738]
102500485  BCL2L11; BCL2 like 11 [KO:K16341]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102500729  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102500813  [KO:K01365] [EC:3.4.22.15]
102500839  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
102500911  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
102501308  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102501396  TUBA3E; tubulin alpha 3e [KO:K07374]
102501462  PRF1; perforin 1 [KO:K07818]
102501703  TNFSF10; tumor necrosis factor superfamily member 10 [KO:K04721]
102501824  HTRA2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
102501850  SPTAN1; spectrin alpha, non-erythrocytic 1 [KO:K06114]
102501936  [KO:K01365] [EC:3.4.22.15]
102501945  NGF; nerve growth factor [KO:K02582]
102502093  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102502622  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
102502813  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102502878  FASLG; Fas ligand [KO:K04389]
102503238  TP53; tumor protein p53 [KO:K04451]
102503296  [KO:K08738]
102503343  [KO:K08738]
102503378  TUBA3D; tubulin alpha 3d [KO:K07374]
106733204  [KO:K08738]
106733869  [KO:K07374]
106734104  [KO:K08738]
106734874  [KO:K08738]
106735223  [KO:K08738]
106735631  [KO:K08738]
106735729  [KO:K08738]
106735920  [KO:K08738]
106736453  [KO:K00922] [EC:2.7.1.153]
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
tup04010  MAPK signaling pathway
tup04020  Calcium signaling pathway
tup04064  NF-kappa B signaling pathway
tup04115  p53 signaling pathway
tup04141  Protein processing in endoplasmic reticulum
tup04151  PI3K-Akt signaling pathway
tup04650  Natural killer cell mediated cytotoxicity
tup04668  TNF signaling pathway
KO pathway
ko04210   

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