KEGG   PATHWAY: pmaj04210
Entry
pmaj04210                   Pathway                                
Name
Apoptosis - Parus major (Great Tit)
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
pmaj04210  Apoptosis
pmaj04210

Other DBs
GO: 0006915
Organism
Parus major (Great Tit) [GN:pmaj]
Gene
107198348  CTSL; cathepsin L1 isoform X2 [KO:K01365] [EC:3.4.22.15]
107198425  LMNB1; lamin-B1 [KO:K07611]
107198526  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
107198580  [KO:K07374]
107198581  [KO:K07374]
107198881  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
107198998  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
107199033  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
107199046  BAX; apoptosis regulator BAX [KO:K02159]
107199939  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
107200701  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
107200910  [KO:K08738]
107201222  BCL2L11; bcl-2-like protein 11 [KO:K16341]
107201442  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107201551  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
107201670  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
107202038  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
107202247  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
107202448  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
107202529  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
107202602  [KO:K08731]
107202925  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107203069  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
107203274  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
107203365  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
107203374  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
107203397  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
107203419  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
107203523  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
107203935  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
107204028  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
107204161  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
107204331  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
107204470  APAF1; apoptotic protease-activating factor 1 isoform X3 [KO:K02084]
107204562  KRAS; GTPase KRas isoform X1 [KO:K07827]
107204618  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
107204914  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107204967  TUBA8; tubulin alpha-8 chain [KO:K07374]
107205132  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
107205249  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
107205253  FADD; FAS-associated death domain protein [KO:K02373]
107205559  HRAS; GTPase HRas [KO:K02833]
107205625  [KO:K04722]
107205807  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107206041  CTSD; cathepsin D isoform X2 [KO:K01379] [EC:3.4.23.5]
107206272  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
107206453  FOS; proto-oncogene c-Fos [KO:K04379]
107206457  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
107206726  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
107206805  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107206851  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
107207062  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
107207226  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
107207333  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
107207334  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
107207386  [KO:K08731]
107207622  TUBA4A; tubulin alpha-4A chain isoform X1 [KO:K07374]
107207877  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
107208073  JUN; transcription factor AP-1 [KO:K04448]
107208273  [KO:K02649]
107208453  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
107208773  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X2 [KO:K03158]
107208827  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107208852  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
107208991  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
107209044  TUBA3C; tubulin alpha-3C chain [KO:K07374]
107209076  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
107209164  [KO:K05692]
107209179  BCL2A1; bcl-2-related protein A1 [KO:K02162]
107209405  [KO:K07611]
107209483  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
107210000  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
107210130  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
107210255  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X3 [KO:K04958]
107210261  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
107210484  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.-]
107210724  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107210777  [KO:K16060]
107211032  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
107211173  ACTB; actin, cytoplasmic 1 [KO:K05692]
107211358  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
107211449  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
107211727  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107211772  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
107212001  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X8 [KO:K06114]
107212003  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
107212066  ENDOG; endonuclease G, mitochondrial [KO:K01173]
107212135  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
107212160  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
107212393  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X3 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
107212453  ACTG1; actin, cytoplasmic 2 [KO:K05692]
107212672  [KO:K16943]
107213248  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
107213269  BCL2L1; bcl-2-like protein 1 [KO:K04570]
107213585  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
107213664  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
107213667  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
107213687  CASP9; caspase-9 isoform X2 [KO:K04399] [EC:3.4.22.62]
107213912  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
107213952  [KO:K04722]
107214529  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
107214592  LMNA; lamin [KO:K12641]
107214633  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
107214698  [KO:K01368] [EC:3.4.22.27]
107214761  NRAS; GTPase NRas [KO:K07828]
107214905  NGF; beta-nerve growth factor [KO:K02582]
107214939  [KO:K07374]
107214964  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
107215027  BAK1; bcl-2 homologous antagonist/killer isoform X2 [KO:K14021]
107215307  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
107215477  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
107215503  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
107215552  LMNB2; lamin-B2 [KO:K07611]
107215603  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
107216262  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107216430  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
117244691  [KO:K04398] [EC:3.4.22.61]
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
pmaj04010  MAPK signaling pathway
pmaj04020  Calcium signaling pathway
pmaj04115  p53 signaling pathway
pmaj04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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