KEGG   PATHWAY: nmel04210
Entry
nmel04210                   Pathway                                
Name
Apoptosis - Numida meleagris (helmeted guineafowl)
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
nmel04210  Apoptosis
nmel04210

Other DBs
GO: 0006915
Organism
Numida meleagris (helmeted guineafowl) [GN:nmel]
Gene
110398962  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
110387170  tumor necrosis factor receptor superfamily member 10A-like isoform X1 [KO:K04722]
110401801  tumor necrosis factor receptor superfamily member 10A-like isoform X1 [KO:K04722]
110402693  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
110400542  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
110401719  FADD; FAS-associated death domain protein [KO:K02373]
110399139  tumor necrosis factor receptor superfamily member 1A-like isoform X1 [KO:K03158]
110404318  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
110400219  CFLAR; LOW QUALITY PROTEIN: CASP8 and FADD-like apoptosis regulator [KO:K04724]
110400694  caspase-8-like [KO:K04398] [EC:3.4.22.61]
110399293  caspase-8-like [KO:K04398] [EC:3.4.22.61]
110400691  caspase-10-like isoform X1 [KO:K04400] [EC:3.4.22.63]
110398619  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
110397291  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110400168  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
110395651  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
110388215  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
110406340  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
110407590  septin-4-like isoform X1 [KO:K16943]
110390926  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
110393943  cytochrome c [KO:K08738]
110400110  cytochrome c, somatic-like isoform X1 [KO:K08738]
110403055  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
110408509  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
110392527  tubulin alpha-3 chain-like [KO:K07374]
110392529  tubulin alpha-3 chain [KO:K07374]
110395666  tubulin alpha-4 chain [KO:K07374]
110395670  tubulin alpha-2 chain isoform X1 [KO:K07374]
110389205  tubulin alpha-1B chain [KO:K07374]
110389220  tubulin alpha-1A chain-like [KO:K07374]
110388184  tubulin alpha-8 chain [KO:K07374]
110397632  tubulin alpha-3 chain [KO:K07374]
110399194  tubulin alpha-4A chain [KO:K07374]
110387955  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
110407139  ACTG1; actin, cytoplasmic 2 [KO:K05692]
110403650  actin, cytoplasmic type 5 [KO:K05692]
110406159  ACTB; actin, cytoplasmic 1 [KO:K05692]
110407072  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
110403944  lamin-L(III)-like isoform X1 [KO:K07611]
110389929  LMNB1; lamin-B1 [KO:K07611]
110388798  LMNB2; lamin-B2 [KO:K07611]
110395273  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070] [EC:2.4.2.30]
110405014  PARP3; poly [ADP-ribose] polymerase 3 isoform X1 [KO:K10798] [EC:2.4.2.30]
110389453  PARP4; poly [ADP-ribose] polymerase 4 isoform X1 [KO:K10798] [EC:2.4.2.30]
110386971  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
110386957  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
110407093  ENDOG; endonuclease G, mitochondrial [KO:K01173]
110403451  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
110407264  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
110405607  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
110406784  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110404652  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110396437  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110388144  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110395367  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
110395702  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
110397823  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
110401065  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
110392532  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110402723  DNA damage-inducible transcript 3 protein-like isoform X1 [KO:K04452]
110395601  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
110390807  CTSC; LOW QUALITY PROTEIN: dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
110401397  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
110403678  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
110388760  cathepsin L1-like isoform X1 [KO:K01365] [EC:3.4.22.15]
110389996  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
110397305  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
110387850  cathepsin S-like [KO:K01368] [EC:3.4.22.27]
110408306  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
110389900  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
110403244  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
110395353  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
110400323  baculoviral IAP repeat-containing protein 5.1-like [KO:K08731]
110408466  BCL2L1; bcl-2-like protein 1 [KO:K04570]
110395041  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
110392996  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
110406964  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
110395802  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
110398630  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110405490  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110399325  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110402812  JUN; transcription factor AP-1 [KO:K04448]
110400992  FOS; proto-oncogene c-Fos [KO:K04379]
110388448  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
110390496  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110387184  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
110401359  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
110398425  NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
110398005  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
110390187  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110388739  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110402857  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
110406931  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
110403833  BCL2A1; bcl-2-related protein A1 [KO:K02162]
110389599  serine-protein kinase ATM-like [KO:K04728] [EC:2.7.11.1]
110401365  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
110390170  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 isoform X1 [KO:K10131]
110398088  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
110388196  NGF; beta-nerve growth factor isoform X1 [KO:K02582]
110388022  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
110391872  cytokine receptor common subunit beta-like isoform X1 [KO:K04738]
110393270  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
110398160  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110397252  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110408755  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
110389564  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110388756  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110402756  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
110405647  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
110396620  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110400745  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110400761  HRAS; GTPase HRas [KO:K02833]
110396332  KRAS; GTPase KRas isoform X1 [KO:K07827]
110388133  NRAS; GTPase NRas [KO:K07828]
110404723  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110404031  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110388854  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110406180  MAPK1; mitogen-activated protein kinase 1 isoform X1 [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
nmel04010  MAPK signaling pathway
nmel04020  Calcium signaling pathway
nmel04115  p53 signaling pathway
nmel04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   
LinkDB

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