KEGG   PATHWAY: etf04210
Entry
etf04210                    Pathway                                
Name
Apoptosis - Echinops telfairi (small Madagascar hedgehog)
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
etf04210  Apoptosis
etf04210

Other DBs
GO: 0006915
Organism
Echinops telfairi (small Madagascar hedgehog) [GN:etf]
Gene
101655233  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
101654642  TNF; tumor necrosis factor [KO:K03156]
101657422  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101643813  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X3 [KO:K03171]
101664220  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X2 [KO:K04724]
101638051  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
101664540  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
101643856  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
101657187  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
101659226  BID; BH3-interacting domain death agonist [KO:K04726]
101646711  BAX; apoptosis regulator BAX [KO:K02159]
101656097  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101648653  diablo homolog, mitochondrial [KO:K10522]
101643317  DIABLO; diablo homolog, mitochondrial [KO:K10522]
101660157  SEPTIN4; septin-4 isoform X5 [KO:K16943]
101649827  LOW QUALITY PROTEIN: uncharacterized protein C17orf47 homolog [KO:K16943]
101644287  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
101661288  cytochrome c, testis-specific [KO:K08738]
101650600  cytochrome c-like [KO:K08738]
101656765  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
101659735  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
101662857  PRF1; perforin-1 [KO:K07818]
101641265  granzyme H [KO:K01353] [EC:3.4.21.79]
101641583  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
101663498  TUBA4A; tubulin alpha-4A chain [KO:K07374]
101640153  tubulin alpha-1D chain [KO:K07374]
101654209  TUBA8; tubulin alpha-8 chain [KO:K07374]
101660474  tubulin alpha-4A chain [KO:K07374]
101651696  LOW QUALITY PROTEIN: tubulin alpha-1C chain [KO:K07374]
101662276  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
101642837  tubulin alpha-3 chain [KO:K07374]
101654715  tubulin alpha-1C chain-like [KO:K07374]
101664407  tubulin alpha-8 chain [KO:K07374]
101654686  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
101659333  LOW QUALITY PROTEIN: actin, cytoplasmic 2-like [KO:K05692]
101640413  SPTAN1; spectrin alpha chain, non-erythrocytic 1 [KO:K06114]
101644090  LMNA; lamin [KO:K12641]
101651821  LMNB1; lamin-B1 [KO:K07611]
101637899  LMNB2; lamin-B2 [KO:K07611]
101654058  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
101660951  PARP4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.30]
101638855  PARP2; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
101641893  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
101638779  DFFA; LOW QUALITY PROTEIN: DNA fragmentation factor subunit alpha [KO:K02310]
101656280  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
101639353  ENDOG; endonuclease G, mitochondrial [KO:K01173]
101655420  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
101660158  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
101643556  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101654141  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101638553  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101657031  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101659155  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
101648937  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
101653369  caspase-12 [KO:K04741] [EC:3.4.22.-]
101641434  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
101639489  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
101650311  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101652164  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
101644265  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
101662901  dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
101654577  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
101647571  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
101655316  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
101656870  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
101663773  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
101641886  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
101642261  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
101656344  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
101638633  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
101651634  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
101655890  baculoviral IAP repeat-containing protein 3 [KO:K16060]
101659133  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
115869468  baculoviral IAP repeat-containing protein 2 [KO:K16060]
101662600  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
115872347  BIRC5; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 5 [KO:K08731]
101663725  BCL2L11; bcl-2-like protein 11 isoform X2 [KO:K16341]
101644838  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101659262  bcl-2-like protein 1 [KO:K04570]
101659722  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101644605  DAXX; death domain-associated protein 6 [KO:K02308]
101652750  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101640716  disabled homolog 2-interacting protein [KO:K19901]
101645193  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
101654493  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101653598  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101645489  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101658729  BAD; bcl2-associated agonist of cell death [KO:K02158]
101656959  JUN; transcription factor AP-1 [KO:K04448]
101656124  FOS; proto-oncogene c-Fos [KO:K04379]
101647784  LOW QUALITY PROTEIN: cellular tumor antigen p53-like [KO:K04451]
101656530  TP53; cellular tumor antigen p53 [KO:K04451]
101650553  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101649582  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101657011  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
101648136  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101656238  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101662652  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101663870  RELA; transcription factor p65 [KO:K04735]
101645397  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
101650390  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101660000  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101641486  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101663447  TRAF1; LOW QUALITY PROTEIN: TNF receptor-associated factor 1 [KO:K03172]
101658117  BCL2A1; bcl-2-related protein A1 isoform X1 [KO:K02162]
101649302  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101649262  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
101659338  BBC3; bcl-2-binding component 3 [KO:K10132]
101657818  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 isoform X2 [KO:K10131]
101643551  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
101658298  NGF; beta-nerve growth factor [KO:K02582]
101647167  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
101639189  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
101641853  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101654217  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101640675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101655654  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101659995  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101657368  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101661509  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101643102  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101649881  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101655315  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101663997  HRAS; GTPase HRas isoform X1 [KO:K02833]
101639926  KRAS; GTPase KRas isoform X3 [KO:K07827]
101649328  GTPase NRas-like [KO:K07828]
101653520  NRAS; GTPase NRas [KO:K07828]
101656360  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
101650474  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101643986  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101648971  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101661786  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
etf04010  MAPK signaling pathway
etf04020  Calcium signaling pathway
etf04064  NF-kappa B signaling pathway
etf04115  p53 signaling pathway
etf04141  Protein processing in endoplasmic reticulum
etf04151  PI3K-Akt signaling pathway
etf04650  Natural killer cell mediated cytotoxicity
etf04668  TNF signaling pathway
KO pathway
ko04210   
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