KEGG   PATHWAY: egz04210
Entry
egz04210                    Pathway                                
Name
Apoptosis - Egretta garzetta (little egret)
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
egz04210  Apoptosis
egz04210

Other DBs
GO: 0006915
Organism
Egretta garzetta (little egret) [GN:egz]
Gene
104132497  TNFSF10; LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 10 [KO:K04721]
104123536  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
104132069  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104129042  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
104124706  FADD; FAS-associated death domain protein [KO:K02373]
104126570  tumor necrosis factor receptor superfamily member 1A-like [KO:K03158]
104130275  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
104130513  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
104130511  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104130512  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
104135531  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
104129473  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
104123620  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
104121759  caspase-3-like [KO:K04397] [EC:3.4.22.60]
104134395  BID; BH3-interacting domain death agonist [KO:K04726]
104125775  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
104122739  DIABLO; diablo homolog, mitochondrial [KO:K10522]
104131768  SEPT4; septin-4 [KO:K16943]
104130002  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
104132707  cytochrome c, somatic [KO:K08738]
104126145  cytochrome c [KO:K08738]
104132316  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
104133155  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
104134393  tubulin alpha-8 chain-like [KO:K07374]
104132418  TUBA4A; LOW QUALITY PROTEIN: tubulin alpha-4A chain [KO:K07374]
104122297  tubulin alpha-3 chain [KO:K07374]
104124941  tubulin alpha-8 chain-like [KO:K07374]
104134378  tubulin alpha-8 chain-like [KO:K07374]
104134810  tubulin alpha-1 chain-like [KO:K07374]
104134829  LOW QUALITY PROTEIN: tubulin alpha-1D chain-like [KO:K07374]
104122004  tubulin alpha-8 chain isoform X1 [KO:K07374]
104130834  actin, cytoplasmic type 5 isoform X1 [KO:K05692]
104132602  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
104132656  actin-like [KO:K05692]
104122534  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
104124057  LMNA; lamin [KO:K12641]
104135327  LMNB1; lamin-B1 [KO:K07611]
104126315  LMNB2; lamin-B2 [KO:K07611]
104130803  lamin-L(III)-like [KO:K07611]
104134588  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
104134718  PARP4; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
104126665  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
104133131  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
104126837  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
104122144  ENDOG; endonuclease G, mitochondrial [KO:K01173]
104134640  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
104123760  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
104134548  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
104124021  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104132649  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
104135140  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104125774  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104132723  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
104124542  CAPN2; LOW QUALITY PROTEIN: calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
104126987  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
104122098  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
104134330  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
104127263  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
104128838  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
104124913  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
104122478  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
104124387  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
104125939  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
104124153  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
104126881  cathepsin S-like [KO:K01368] [EC:3.4.22.27]
104130672  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
104128906  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
104124100  XIAP; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104128140  BCL2L11; bcl-2-like protein 11 [KO:K16341]
104130016  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
104122827  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
104135225  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
104131143  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
104129145  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104128427  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104133994  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
104123944  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
104132232  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
104125140  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
104135306  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104133251  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104122596  LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit-like [KO:K02580]
104128551  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
104126926  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104135230  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
104123595  BCL2A1; bcl-2-related protein A1 [KO:K02162]
104130058  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
104127053  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
104133908  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
104126551  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
104126776  NGF; beta-nerve growth factor [KO:K02582]
104134295  CSF2RB; LOW QUALITY PROTEIN: cytokine receptor common subunit beta [KO:K04738]
104133065  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104135481  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104129991  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104135641  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
104124880  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104126253  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104131301  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
104131524  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104125648  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104123569  HRAS; GTPase HRas [KO:K02833]
104135137  KRAS; GTPase KRas isoform X1 [KO:K07827]
104126779  NRAS; GTPase NRas [KO:K07828]
104124306  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
104133527  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104124397  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104127223  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
  Authors
Savitskaya MA, Onishchenko GE
  Title
Mechanisms of Apoptosis.
  Journal
Biochemistry (Mosc) 80:1393-417 (2015)
DOI:10.1134/S0006297915110012
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Safa AR
  Title
c-FLIP, a master anti-apoptotic regulator.
  Journal
Exp Oncol 34:176-84 (2012)
Reference
  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
  Authors
Parsons MJ, Green DR
  Title
Mitochondria in cell death.
  Journal
Essays Biochem 47:99-114 (2010)
DOI:10.1042/bse0470099
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Logue SE, Martin SJ
  Title
Caspase activation cascades in apoptosis.
  Journal
Biochem Soc Trans 36:1-9 (2008)
DOI:10.1042/BST0360001
Reference
  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
  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
egz04010  MAPK signaling pathway
egz04020  Calcium signaling pathway
egz04115  p53 signaling pathway
egz04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   
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