KEGG   PATHWAY: tpai04210
Entry
tpai04210                   Pathway                                
Name
Apoptosis - Tympanuchus pallidicinctus (lesser prairie-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
tpai04210  Apoptosis
tpai04210

Other DBs
GO: 0006915
Organism
Tympanuchus pallidicinctus (lesser prairie-chicken) [GN:tpai]
Gene
128071868  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
128071898  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
128071928  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
128071993  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
128072016  [KO:K12641]
128072024  LMNA; LOW QUALITY PROTEIN: lamin [KO:K12641]
128072298  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
128072383  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
128072448  JUN; transcription factor Jun [KO:K04448]
128072661  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
128072770  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
128073067  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
128073089  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
128073364  [KO:K07374]
128073373  [KO:K07374]
128073375  BID; BH3-interacting domain death agonist [KO:K04726]
128073589  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
128073632  [KO:K04738]
128073635  [KO:K04738]
128074076  ENDOG; endonuclease G, mitochondrial [KO:K01173]
128074089  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
128074106  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
128074167  [KO:K07374]
128074168  TUBA1A; tubulin alpha-1A chain [KO:K07374]
128074169  [KO:K07374]
128074258  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
128074427  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
128074595  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
128074790  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
128074803  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
128074930  PARP4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
128075115  [KO:K07611]
128075170  [KO:K05692]
128075192  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
128075211  BCL2A1; bcl-2-related protein A1 [KO:K02162]
128075267  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128075530  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
128075890  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
128076189  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
128076243  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
128076633  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
128076767  [KO:K07374]
128077107  [KO:K08731]
128077294  [KO:K04400] [EC:3.4.22.63]
128077302  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
128077303  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
128077304  [KO:K04398] [EC:3.4.22.61]
128077706  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
128077974  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
128077983  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128078052  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
128078344  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
128078363  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128078470  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.-]
128078817  [KO:K04452]
128078925  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
128078974  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
128079246  ACTB; actin, cytoplasmic 1 [KO:K05692]
128079690  [KO:K07374]
128079771  PRF1; perforin-1 isoform X1 [KO:K07818]
128079775  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
128079966  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
128079967  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
128080186  PLA2G12A; group XIIA secretory phospholipase A2 isoform X1 [KO:K04396] [EC:3.4.22.59]
128080653  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
128080681  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
128080741  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
128080968  BCL2L1; bcl-2-like protein 1 [KO:K04570]
128081241  CTSZ; LOW QUALITY PROTEIN: cathepsin Z [KO:K08568] [EC:3.4.18.1]
128081756  TRADD; LOW QUALITY PROTEIN: tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
128081922  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
128082400  [KO:K07374]
128082424  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128082641  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128083066  ACTG1; actin, cytoplasmic 2 [KO:K05692]
128083281  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
128083510  SEPTIN4; septin-4 isoform X1 [KO:K16943]
128083876  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
128084385  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
128084490  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
128084496  KRAS; GTPase KRas isoform X1 [KO:K07827]
128084543  BCL2L11; bcl-2-like protein 11 [KO:K16341]
128084585  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128084754  DIABLO; diablo IAP-binding mitochondrial protein [KO:K10522]
128084838  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128084844  DFFA; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
128085014  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
128085089  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
128085411  CAPN11; calpain-11 isoform X1 [KO:K01367] [EC:3.4.22.52]
128085415  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
128085485  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
128085762  [KO:K08738]
128085876  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128085952  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
128086364  HRAS; GTPase HRas [KO:K02833]
128086469  FADD; FAS-associated death domain protein [KO:K02373]
128086496  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
128086784  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128086835  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
128086968  FOS; protein c-Fos [KO:K04379]
128087365  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
128087719  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
128087755  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
128087993  NGF; beta-nerve growth factor [KO:K02582]
128088141  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
128088157  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
128088218  NRAS; GTPase NRas [KO:K07828]
128088788  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
128088872  [KO:K01365] [EC:3.4.22.15]
128088947  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
128088982  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128089542  LMNB1; lamin-B1 [KO:K07611]
128089608  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
128089621  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
128089920  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
128090036  [KO:K04722]
128090122  LMNB2; lamin-B2 isoform X1 [KO:K07611]
128090309  [KO:K07374]
128090447  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
128090579  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
128092059  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
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
tpai04010  MAPK signaling pathway
tpai04020  Calcium signaling pathway
tpai04115  p53 signaling pathway
tpai04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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