KEGG   PATHWAY: gga04210
Entry
gga04210                    Pathway                                
Name
Apoptosis - Gallus gallus (chicken)
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
gga04210  Apoptosis
gga04210

Other DBs
GO: 0006915
Organism
Gallus gallus (chicken) [GN:gga]
Gene
378894  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
373904  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B precursor [KO:K04722]
429064  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
395274  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
423146  FADD; FAS-associated death domain protein [KO:K02373]
418325  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
415700  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
424080  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
395284  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
693266  CASP18; initiator caspase [KO:K04398] [EC:3.4.22.61]
424081  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
395477  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
395476  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
423901  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
395236  BID; BH3-interacting domain death agonist [KO:K04726]
419912  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
416860  DIABLO; diablo homolog, mitochondrial isoform X2 [KO:K10522]
770762  SEPT4; septin-4 isoform X3 [KO:K16943]
395990  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
420624  CYCS; cytochrome c [KO:K08738]
417926  APAF1; apoptotic protease-activating factor 1 isoform X3 [KO:K02084]
426970  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
101750363  PRF1; perforin-1 isoform X2 [KO:K07818]
396426  TUBA8B; tubulin alpha-2 chain [KO:K07374]
416695  tubulin alpha chain [KO:K07374]
418166  TUBA8A; tubulin alpha-4 chain [KO:K07374]
421169  TUBA3E; tubulin alpha-8 chain [KO:K07374]
425049  tubulin alpha-3 chain [KO:K07374]
100857247  TUBA4A; tubulin alpha-5 chain-like [KO:K07374]
416694  TUBAL3; tubulin alpha-3 chain [KO:K07374]
100859737  TUBA1A1; tubulin alpha-1B chain [KO:K07374]
429035  TUBA1C; tubulin alpha-1 chain [KO:K07374]
100857858  TUBA1C; tubulin alpha-1C chain [KO:K07374]
100857214  TUBA4B; tubulin alpha-4A chain [KO:K07374]
395674  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform 1 [KO:K02539]
776816  actin, cytoplasmic 2 [KO:K05692]
415296  ACTG1; actin, cytoplasmic type 5 [KO:K05692]
396526  ACTB; actin, cytoplasmic 1 [KO:K05692]
374234  SPTAN1; spectrin alpha chain, non-erythrocytic 1 [KO:K06114]
396224  lamin-A [KO:K12641]
396222  LMNB2; lamin-B2 [KO:K07611]
396223  LMNB1; lamin-B1 [KO:K07611]
415464  LMINA; lamin-L(III) isoform X1 [KO:K07611]
396199  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
418958  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
771158  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
419451  DFFA; DNA fragmentation factor subunit alpha isoform X2 [KO:K02310]
374158  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
417204  ENDOG; endonuclease G, mitochondrial [KO:K01173]
428688  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
771230  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 precursor [KO:K08852] [EC:2.7.11.1 3.1.26.-]
417414  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 precursor [KO:K08852] [EC:2.7.11.1 3.1.26.-]
417287  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
395412  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
418212  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
419910  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
396240  CAPN11; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
693249  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
395963  CAPN2; calpain-2 catalytic subunit precursor [KO:K03853] [EC:3.4.22.53]
422930  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
423279  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
395693  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100857832  DDIT3; uncharacterized protein DDIT3 [KO:K04452]
396329  CTSB; cathepsin B precursor [KO:K01363] [EC:3.4.22.1]
419014  CTSC; dipeptidyl peptidase 1 precursor [KO:K01275] [EC:3.4.14.1]
396090  CTSD; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
770109  CTSH; pro-cathepsin H precursor [KO:K01366] [EC:3.4.22.16]
395818  CTSK; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
427466  CTSV; cathepsin L1 precursor [KO:K01365] [EC:3.4.22.15]
420160  cathepsin L1-like isoform 1 precursor [KO:K01365] [EC:3.4.22.15]
422410  CTSO; cathepsin O precursor [KO:K01374] [EC:3.4.22.42]
425657  CTSS; cathepsin S precursor [KO:K01368] [EC:3.4.22.27]
419311  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
374012  BIRC2; inhibitor of apoptosis protein [KO:K16060]
395280  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
374078  BIRC5; survivin isoform 1 [KO:K08731]
768589  baculoviral IAP repeat-containing protein 5.1 [KO:K08731]
107052854  BCL2L11; bcl-2-like protein 11 [KO:K16341]
373954  BCL2L1; bcl-2-like protein 1 [KO:K04570]
396282  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
378921  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
417117  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
421688  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
423778  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
395983  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
422592  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
424673  JUN; transcription factor AP-1 [KO:K04448]
396512  FOS; proto-oncogene c-Fos [KO:K04379]
419964  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
423669  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
426792  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
396093  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
396033  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
396027  RELA; transcription factor p65 [KO:K04735]
422591  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
693255  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
429929  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100859853  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
417123  TRAF1; TNF receptor-associated factor 1 isoform X4 [KO:K03172]
395673  BCL2A1; bcl-2-related protein A1 [KO:K02162]
395401  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
426464  LRRC27; LOW QUALITY PROTEIN: p53-induced death domain-containing protein 1 [KO:K10130]
770077  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
395857  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
396466  NGF; beta-nerve growth factor precursor [KO:K02582]
396337  NTRK1; high affinity nerve growth factor receptor precursor [KO:K03176] [EC:2.7.10.1]
771315  CRCBL; cytokine receptor common subunit beta isoform X1 [KO:K04738]
101750812  CSF2RB; cytokine receptor common subunit beta-like isoform X1 [KO:K04738]
424971  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
419444  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
424826  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
429096  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
771142  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
427171  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
416588  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
395928  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
421497  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101750560  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
396229  HRAS; GTPase HRas precursor [KO:K02833]
418207  KRAS; GTPase KRas [KO:K07827]
419885  NRAS; GTPase NRas precursor [KO:K07828]
396245  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
415549  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
396349  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
373953  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
gga04010  MAPK signaling pathway
gga04020  Calcium signaling pathway
gga04115  p53 signaling pathway
gga04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

  All links  
Genome (1)   
   KEGG GENOME (1)   
Gene (125)   
   KEGG GENES (125)   
All databases (126)   

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