KEGG   PATHWAY: phi04210
Entry
phi04210                    Pathway                                
Name
Apoptosis - Pseudopodoces humilis (Tibetan ground-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
phi04210  Apoptosis
phi04210

Other DBs
GO: 0006915
Organism
Pseudopodoces humilis (Tibetan ground-tit) [GN:phi]
Gene
102099156  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102099159  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
102099328  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
102099356  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
102099369  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102099539  LMNB2; lamin-B2 [KO:K07611]
102099764  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
102099885  BCL2L11; bcl-2-like protein 11 [KO:K16341]
102100562  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102100585  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
102100672  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
102100681  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102100874  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
102101024  [KO:K07611]
102101117  [KO:K04722]
102101219  HRAS; GTPase HRas [KO:K02833]
102101400  [KO:K08731]
102101491  TP53; cellular tumor antigen p53 [KO:K04451]
102101552  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
102101979  [KO:K07374]
102101987  LMNA; lamin [KO:K12641]
102102166  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102102206  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
102102219  FADD; FAS-associated death domain protein [KO:K02373]
102102285  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102102341  [KO:K07374]
102102426  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
102102492  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102102693  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
102102778  [KO:K07374]
102102785  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
102102818  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102102822  BCL2L1; bcl-2-like protein 1 [KO:K04570]
102103178  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
102103181  FOS; proto-oncogene c-Fos [KO:K04379]
102103433  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
102103505  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
102103547  [KO:K04722]
102103635  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102103785  [KO:K07374]
102103825  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102103849  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
102103964  [KO:K07374]
102104024  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
102104037  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102104081  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X2 [KO:K04426] [EC:2.7.11.25]
102104322  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
102104432  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
102104585  SEPT4; septin-4 [KO:K16943]
102104813  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102104823  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
102105014  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
102105236  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
102105321  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
102105587  LMNB1; lamin-B1 [KO:K07611]
102105760  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
102105884  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
102105891  RELA; transcription factor p65 [KO:K04735]
102106020  BAX; apoptosis regulator BAX [KO:K02159]
102106238  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
102106384  TRAF2; TNF receptor-associated factor 2 isoform X4 [KO:K03173] [EC:2.3.2.27]
102106412  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
102106589  [KO:K01379] [EC:3.4.23.5]
102106643  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102106742  ACTB; actin, cytoplasmic 1 [KO:K05692]
102106744  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102106799  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.-]
102106897  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102107154  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
102107463  DAXX; death domain-associated protein 6 [KO:K02308]
102107552  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X7 [KO:K06114]
102107665  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102107798  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102107801  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
102107854  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102107913  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
102107924  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
102107950  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102108085  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
102108213  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
102108387  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
102108950  CASP9; caspase-9 isoform X2 [KO:K04399] [EC:3.4.22.62]
102109074  ENDOG; endonuclease G, mitochondrial [KO:K01173]
102109497  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102109500  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102109553  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102109715  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102110075  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102110157  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
102110239  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
102110255  [KO:K05692]
102110285  NRAS; GTPase NRas [KO:K07828]
102110606  BID; BH3-interacting domain death agonist isoform X2 [KO:K04726]
102110759  [KO:K04398] [EC:3.4.22.61]
102110794  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
102110798  TUBA8; tubulin alpha-8 chain [KO:K07374]
102111062  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
102111224  ACTG1; actin, cytoplasmic 2 [KO:K05692]
102111404  NGF; beta-nerve growth factor [KO:K02582]
102111446  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
102111555  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
102111696  [KO:K08731]
102112236  JUN; transcription factor AP-1 [KO:K04448]
102112318  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102112432  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
102112480  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
102112482  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
102112802  BCL2A1; bcl-2-related protein A1 [KO:K02162]
102112828  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102112893  KRAS; GTPase KRas [KO:K07827]
102113116  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102113262  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
102113463  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X2 [KO:K04466] [EC:2.7.11.25]
102113646  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
102113796  [KO:K08738]
102113899  [KO:K07210]
102114064  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
102114428  [KO:K07374]
102114724  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102114750  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
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
phi04010  MAPK signaling pathway
phi04020  Calcium signaling pathway
phi04115  p53 signaling pathway
phi04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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