KEGG   PATHWAY: svg04210
Entry
svg04210                    Pathway                                
Name
Apoptosis - Sturnus vulgaris (common starling)
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
svg04210  Apoptosis
svg04210

Other DBs
GO: 0006915
Organism
Sturnus vulgaris (common starling) [GN:svg]
Gene
106859651  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
106863437  TNFRSF10B; LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 10B [KO:K04722]
106852213  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
106852662  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
106854799  FADD; FAS-associated death domain protein [KO:K02373]
106860847  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
106855856  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
106855084  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
106855086  caspase-8-like [KO:K04398] [EC:3.4.22.61]
106855095  caspase-8-like [KO:K04398] [EC:3.4.22.61]
106855085  caspase-10-like isoform X1 [KO:K04400] [EC:3.4.22.63]
106854398  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
106861352  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
106850873  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
106849436  BID; BH3-interacting domain death agonist [KO:K04726]
106864241  BAX; apoptosis regulator BAX [KO:K02159]
106851021  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
106852384  DIABLO; diablo homolog, mitochondrial [KO:K10522]
106856235  SEPT4; septin-4 [KO:K16943]
106853114  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
106864714  cytochrome c [KO:K08738]
106861312  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
106856421  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
106864005  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
106862679  tubulin alpha-1B chain isoform X1 [KO:K07374]
106859147  tubulin alpha-3 chain-like [KO:K07374]
106849434  TUBA8; tubulin alpha-8 chain [KO:K07374]
106860311  TUBA4A; tubulin alpha-4A chain [KO:K07374]
106851107  tubulin alpha-8 chain [KO:K07374]
106856863  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
106861137  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
106849796  ACTB; actin, cytoplasmic 1 [KO:K05692]
106859911  ACTG1; actin, cytoplasmic 2 [KO:K05692]
106861064  actin, cytoplasmic type 5 [KO:K05692]
106851323  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
106861140  LMNA; lamin [KO:K12641]
106857630  LMNB1; lamin-B1 [KO:K07611]
106857969  LMNB2; lamin-B2 [KO:K07611]
106860087  lamin-L(III)-like isoform X1 [KO:K07611]
106853919  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
106849132  PARP3; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
106862710  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
106857693  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
106851331  ENDOG; endonuclease G, mitochondrial [KO:K01173]
106862175  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
106854307  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
106859281  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
106855986  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
106851697  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
106860950  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
106851022  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
106863566  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
106854259  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
106853912  CAPN2; calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
106853142  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
106849054  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
106858572  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
106862637  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
106863201  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
106853973  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
106863276  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
106860153  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
106862381  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
106848905  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
106857522  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
106862353  cathepsin S-like [KO:K01368] [EC:3.4.22.27]
106851706  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
106859379  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
106859213  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
106855089  baculoviral IAP repeat-containing protein 5.1-like [KO:K08731]
106857292  baculoviral IAP repeat-containing protein 5-like [KO:K08731]
106865143  BCL2L11; bcl-2-like protein 11 [KO:K16341]
106861623  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
106850823  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
106850789  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
106855393  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
106854874  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
106852620  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
106859575  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
106855713  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
106849741  JUN; transcription factor AP-1 [KO:K04448]
106861661  FOS; proto-oncogene c-Fos [KO:K04379]
106858264  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
106856724  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
106862058  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
106862084  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
106852538  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
106863554  RELA; transcription factor p65 [KO:K04735]
106855709  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
106848923  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
106857131  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
106862212  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
106855421  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
106859245  BCL2A1; bcl-2-related protein A1 [KO:K02162]
106854003  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
106851559  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
106852706  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
106863051  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
106850961  NGF; beta-nerve growth factor [KO:K02582]
106861108  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
106858564  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
106858869  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106849578  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
106850308  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106850601  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
106856206  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
106857134  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
106859269  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
106854253  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
106850505  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106851547  HRAS; GTPase HRas [KO:K02833]
106860955  KRAS; GTPase KRas isoform X1 [KO:K07827]
106851063  NRAS; GTPase NRas [KO:K07828]
106849281  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
106852168  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
106859747  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106864856  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
svg04010  MAPK signaling pathway
svg04020  Calcium signaling pathway
svg04115  p53 signaling pathway
svg04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system