KEGG   PATHWAY: nle04210
Entry
nle04210                    Pathway                                
Name
Apoptosis - Nomascus leucogenys (northern white-cheeked gibbon)
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
nle04210  Apoptosis
nle04210

Other DBs
GO: 0006915
Organism
Nomascus leucogenys (northern white-cheeked gibbon) [GN:nle]
Gene
100602881  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A [KO:K04722]
105740159  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B [KO:K04722]
100597719  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
100580318  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
100607557  FADD; FAS-associated death domain protein [KO:K02373]
100583968  TNF; tumor necrosis factor [KO:K03156]
100581749  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X4 [KO:K03158]
100607674  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
100589650  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X2 [KO:K04724]
100586183  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
100585413  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
100591774  CASP6; caspase-6 isoform X2 [KO:K04396] [EC:3.4.22.59]
100585064  CASP3; caspase-3 isoform X3 [KO:K02187] [EC:3.4.22.56]
100580571  BID; BH3-interacting domain death agonist [KO:K04726]
100593013  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100588483  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100604539  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
100580310  SEPTIN4; septin-4 isoform X2 [KO:K16943]
115830458  septin-4-like isoform X1 [KO:K16943]
100581739  uncharacterized protein C17orf47 [KO:K16943]
100591213  HTRA2; serine protease HTRA2, mitochondrial isoform X2 [KO:K08669] [EC:3.4.21.108]
100603746  cytochrome c-like [KO:K08738]
100600457  cytochrome c-like [KO:K08738]
100580069  cytochrome c [KO:K08738]
100598207  cytochrome c-like [KO:K08738]
100599727  cytochrome c-like [KO:K08738]
101179576  cytochrome c-like [KO:K08738]
100604294  cytochrome c-like [KO:K08738]
100590369  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
100597173  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
100603797  PRF1; perforin-1 [KO:K07818]
100604300  GZMB; granzyme B isoform X1 [KO:K01353] [EC:3.4.21.79]
100602904  TUBAL3; tubulin alpha chain-like 3 isoform X1 [KO:K07374]
100582452  TUBA8; tubulin alpha-8 chain [KO:K07374]
100585215  tubulin alpha-3 chain [KO:K07374]
100587604  tubulin alpha-3 chain [KO:K07374]
100599731  TUBA4B; putative tubulin-like protein alpha-4B [KO:K07374]
100602647  tubulin alpha-1C chain isoform X1 [KO:K07374]
100583522  TUBA4A; tubulin alpha-4A chain isoform X1 [KO:K07374]
100592992  TUBA3E; tubulin alpha-3E chain [KO:K07374]
100585634  tubulin alpha-1A chain [KO:K07374]
100604350  tubulin alpha-1B chain [KO:K07374]
100604947  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
100598167  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100598411  ACTB; actin, cytoplasmic 1 [KO:K05692]
100601499  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
100603145  LMNA; lamin [KO:K12641]
100584344  LMNB1; lamin-B1 [KO:K07611]
100582220  LMNB2; lamin-B2 [KO:K07611]
100594648  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
100591855  PARP2; poly [ADP-ribose] polymerase 2 isoform X2 [KO:K10798] [EC:2.4.2.30]
100580089  PARP4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.30]
100597938  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.30]
100601546  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
100594905  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
100602842  ENDOG; endonuclease G, mitochondrial isoform X1 [KO:K01173]
100605967  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
100606427  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
100590721  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
100587159  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100599135  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
100585914  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100605026  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
100589114  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100587073  LOW QUALITY PROTEIN: inactive caspase-12 [KO:K04741] [EC:3.4.22.-]
100589743  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
100587728  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
100588160  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100600067  DDIT3; DNA damage-inducible transcript 3 protein isoform X1 [KO:K04452]
100604807  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
100599280  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
100582697  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
100597028  CTSF; LOW QUALITY PROTEIN: cathepsin F [KO:K01373] [EC:3.4.22.41]
100584322  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
100580351  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
100604414  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
100584986  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
100579205  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
100586899  CTSV; cathepsin L2 [KO:K01375] [EC:3.4.22.43]
100581304  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
100605843  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
100579740  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
100580307  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100597865  XIAP; E3 ubiquitin-protein ligase XIAP isoform X4 [KO:K04725] [EC:2.3.2.27]
100598415  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
100594069  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
100595330  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100599011  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100583518  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
100599272  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
100591971  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
100587332  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
100581677  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100605285  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100602081  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
101178725  BAD; bcl2-associated agonist of cell death [KO:K02158]
100586501  JUN; transcription factor AP-1 [KO:K04448]
100585899  FOS; proto-oncogene c-Fos [KO:K04379]
100583326  TP53; cellular tumor antigen p53 [KO:K04451]
101178309  HRK; activator of apoptosis harakiri [KO:K02512]
100600394  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X2 [KO:K04466] [EC:2.7.11.25]
100596225  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100588081  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100603768  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100599351  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100581655  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100588439  RELA; transcription factor p65 [KO:K04735]
100603082  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X2 [KO:K02374]
100593432  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100583800  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
115830865  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100605879  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
100587457  BCL2A1; bcl-2-related protein A1 [KO:K02162]
100599114  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
101178913  TP53AIP1; LOW QUALITY PROTEIN: p53-regulated apoptosis-inducing protein 1 [KO:K13773]
100588342  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
100593765  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
100599260  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
100593913  NGF; beta-nerve growth factor [KO:K02582]
100585466  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
100593178  IL3; interleukin-3 [KO:K04736]
100594820  CSF2RB; cytokine receptor common subunit beta isoform X2 [KO:K04738]
100588218  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100580872  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100584384  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100605788  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100591270  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100599301  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100593010  3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
115831277  LOW QUALITY PROTEIN: putative 3-phosphoinositide-dependent protein kinase 2 [KO:K06276] [EC:2.7.11.1]
100604331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100587864  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100587109  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100595274  HRAS; GTPase HRas isoform X1 [KO:K02833]
100593773  KRAS; GTPase KRas isoform X1 [KO:K07827]
100592103  NRAS; GTPase NRas [KO:K07828]
100582599  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100579506  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100591827  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100600574  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100584480  MAPK3; mitogen-activated protein kinase 3 [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
nle04010  MAPK signaling pathway
nle04020  Calcium signaling pathway
nle04064  NF-kappa B signaling pathway
nle04115  p53 signaling pathway
nle04141  Protein processing in endoplasmic reticulum
nle04151  PI3K-Akt signaling pathway
nle04650  Natural killer cell mediated cytotoxicity
nle04668  TNF signaling pathway
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system