KEGG   PATHWAY: dro04210
dro04210                    Pathway                                

Apoptosis - Desmodus rotundus (common vampire bat)
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.
Cellular Processes; Cell growth and death
Pathway map
dro04210  Apoptosis

Other DBs
GO: 0006915
Desmodus rotundus (common vampire bat) [GN:dro]
112307528  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
112305008  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
112317424  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
112297049  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
112307358  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
112317320  FADD; FAS-associated death domain protein [KO:K02373]
112302067  TNF; tumor necrosis factor isoform X1 [KO:K03156]
112321955  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
112300831  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
112307654  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
112307787  CASP8; caspase-8 [KO:K04398] [EC:]
112308028  CASP10; caspase-10 [KO:K04400] [EC:]
112296279  CASP6; caspase-6 [KO:K04396] [EC:]
112306749  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:]
112300184  CASP7; caspase-7 [KO:K04397] [EC:]
112310499  BID; BH3-interacting domain death agonist [KO:K04726]
112310132  BAX; apoptosis regulator BAX [KO:K02159]
112302219  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
112310731  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
112316363  SEPT4; septin-4 isoform X1 [KO:K16943]
112303094  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:]
112306993  cytochrome c [KO:K08738]
112320658  cytochrome c-like [KO:K08738]
112322221  cytochrome c-like [KO:K08738]
112321814  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
112299456  CASP9; caspase-9 [KO:K04399] [EC:]
112305296  PRF1; perforin-1 [KO:K07818]
112296490  granzyme B-like [KO:K01353] [EC:]
112296591  granzyme H-like [KO:K01353] [EC:]
112321272  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
112301806  tubulin alpha-3 chain [KO:K07374]
112318638  tubulin alpha-1A chain [KO:K07374]
112318639  TUBA1B; tubulin alpha-1B chain [KO:K07374]
112311601  TUBA8; tubulin alpha-8 chain [KO:K07374]
112301743  tubulin alpha-3 chain-like [KO:K07374]
112307747  tubulin alpha-4A chain [KO:K07374]
112318375  tubulin alpha-1C chain [KO:K07374]
112307926  tubulin alpha-1D chain-like [KO:K07374]
112313500  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
112298712  ACTG1; actin, cytoplasmic 2 [KO:K05692]
112319437  ACTB; actin, cytoplasmic 1 [KO:K05692]
112317643  SPTA1; spectrin alpha chain, erythrocytic 1 [KO:K06114]
112306217  SPTAN1; spectrin alpha chain, non-erythrocytic 1 [KO:K06114]
112317116  LMNA; lamin [KO:K12641]
112312400  LMNB2; lamin-B2 [KO:K07611]
112314999  LMNB1; lamin-B1 isoform X1 [KO:K07611]
112318849  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:]
112309615  poly [ADP-ribose] polymerase 3-like [KO:K10798] [EC:]
112296223  PARP4; poly [ADP-ribose] polymerase 4 isoform X1 [KO:K10798] [EC:]
112309686  poly [ADP-ribose] polymerase 3-like [KO:K10798] [EC:]
112311715  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:]
112299099  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
112299050  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
112306414  ENDOG; endonuclease G, mitochondrial [KO:K01173]
112310632  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
112316288  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC: 3.1.26.-]
112306448  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:]
112309625  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
112318382  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
112302101  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
112317121  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:]
112318759  calpain-2 catalytic subunit [KO:K03853] [EC:]
112314270  caspase-12-like [KO:K04741] [EC:3.4.22.-]
112297566  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:]
112311304  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
112321682  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112319047  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
112312250  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:]
112316040  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:]
112317266  CTSD; cathepsin D [KO:K01379] [EC:]
112317103  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:]
112305948  CTSH; pro-cathepsin H [KO:K01366] [EC:]
112313792  CTSK; cathepsin K [KO:K01371] [EC:]
112302733  CTSV; LOW QUALITY PROTEIN: cathepsin L2 [KO:K01365] [EC:]
112302874  cathepsin L1-like [KO:K01365] [EC:]
112312320  CTSO; cathepsin O [KO:K01374] [EC:]
112313687  CTSS; cathepsin S [KO:K01368] [EC:]
112317264  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
112304016  CTSZ; cathepsin Z [KO:K08568] [EC:]
112317544  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
112317519  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
112310530  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:]
112302993  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 5-like [KO:K08731]
112298801  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
112319403  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
112304196  BCL2L1; bcl-2-like protein 1 [KO:K04570]
112322759  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
112302087  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
112297551  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:]
112306355  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
112297079  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:]
112296379  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
112305558  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
112317841  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
112317275  BAD; bcl2-associated agonist of cell death [KO:K02158]
112314642  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
112311412  FOS; proto-oncogene c-Fos [KO:K04379]
112308825  TP53; cellular tumor antigen p53 [KO:K04451]
112298609  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:]
112300474  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:]
112321547  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:]
112296261  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112296519  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112317867  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112317202  RELA; transcription factor p65 [KO:K04735]
112317765  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
112312410  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112307265  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112312272  growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402]
112309280  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112306476  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
112306083  bcl-2-related protein A1-like [KO:K02162]
112314280  ATM; serine-protein kinase ATM [KO:K04728] [EC:]
112317131  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
112312833  BBC3; bcl-2-binding component 3 [KO:K10132]
112316166  CASP2; caspase-2 [KO:K02186] [EC:]
112313781  NGF; beta-nerve growth factor [KO:K02582]
112315668  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:]
112301616  IL3; interleukin-3 [KO:K04736]
112313317  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
112322009  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
112310002  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:]
112299448  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
112307667  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
112321016  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112305224  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112314466  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
112298319  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:]
112311458  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
112318919  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
112320130  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
112317099  HRAS; GTPase HRas isoform X1 [KO:K02833]
112318275  KRAS; LOW QUALITY PROTEIN: GTPase KRas [KO:K07827]
112304041  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
112313707  NRAS; GTPase NRas [KO:K07828]
112301126  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
112311345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
112312483  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
112304801  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
112301746  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
C00027  Hydrogen peroxide
C00076  Calcium cation
C00319  Sphingosine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Savitskaya MA, Onishchenko GE
Mechanisms of Apoptosis.
Biochemistry (Mosc) 80:1393-417 (2015)
Schleich K, Lavrik IN
Mathematical modeling of apoptosis.
Cell Commun Signal 11:44 (2013)
Lavrik I, Golks A, Krammer PH
Death receptor signaling.
J Cell Sci 118:265-7 (2005)
Jin Z, El-Deiry WS
Overview of cell death signaling pathways.
Cancer Biol Ther 4:139-63 (2005)
Benn SC, Woolf CJ
Adult neuron survival strategies--slamming on the brakes.
Nat Rev Neurosci 5:686-700 (2004)
Orrenius S, Zhivotovsky B, Nicotera P
Regulation of cell death: the calcium-apoptosis link.
Nat Rev Mol Cell Biol 4:552-65 (2003)
Clarke P, Tyler KL
Apoptosis in animal models of virus-induced disease.
Nat Rev Microbiol 7:144-55 (2009)
Wen X, Lin ZQ, Liu B, Wei YQ
Caspase-mediated programmed cell death pathways as potential therapeutic targets in cancer.
Cell Prolif 45:217-24 (2012)
Shalini S, Dorstyn L, Dawar S, Kumar S
Old, new and emerging functions of caspases.
Cell Death Differ 22:526-39 (2015)
Philchenkov A
Caspases: potential targets for regulating cell death.
J Cell Mol Med 8:432-44 (2004)
Stroh C, Schulze-Osthoff K
Death by a thousand cuts: an ever increasing list of caspase substrates.
Cell Death Differ 5:997-1000 (1998)
Safa AR
c-FLIP, a master anti-apoptotic regulator.
Exp Oncol 34:176-84 (2012)
Jeong SY, Seol DW
The role of mitochondria in apoptosis.
BMB Rep 41:11-22 (2008)
Parsons MJ, Green DR
Mitochondria in cell death.
Essays Biochem 47:99-114 (2010)
Strasser A
The role of BH3-only proteins in the immune system.
Nat Rev Immunol 5:189-200 (2005)
Schonthal AH
Endoplasmic reticulum stress: its role in disease and novel prospects for therapy.
Scientifica (Cairo) 2012:857516 (2012)
Malhi H, Kaufman RJ
Endoplasmic reticulum stress in liver disease.
J Hepatol 54:795-809 (2011)
Malhotra JD, Kaufman RJ
The endoplasmic reticulum and the unfolded protein response.
Semin Cell Dev Biol 18:716-31 (2007)
Wu J, Kaufman RJ
From acute ER stress to physiological roles of the Unfolded Protein Response.
Cell Death Differ 13:374-84 (2006)
Repnik U, Stoka V, Turk V, Turk B
Lysosomes and lysosomal cathepsins in cell death.
Biochim Biophys Acta 1824:22-33 (2012)
Cesen MH, Pegan K, Spes A, Turk B
Lysosomal pathways to cell death and their therapeutic applications.
Exp Cell Res 318:1245-51 (2012)
Dashzeveg N, Yoshida K
Cell death decision by p53 via control of the mitochondrial membrane.
Cancer Lett 367:108-12 (2015)
Bouchier-Hayes L, Green DR
Caspase-2: the orphan caspase.
Cell Death Differ 19:51-7 (2012)
Baptiste-Okoh N, Barsotti AM, Prives C
A role for caspase 2 and PIDD in the process of p53-mediated apoptosis.
Proc Natl Acad Sci U S A 105:1937-42 (2008)
Aggarwal BB
Signalling pathways of the TNF superfamily: a double-edged sword.
Nat Rev Immunol 3:745-56 (2003)
Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA.
JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis.
Leukemia 18:189-218 (2004)
Dragovich T, Rudin CM, Thompson CB
Signal transduction pathways that regulate cell survival and cell death.
Oncogene 17:3207-13 (1998)
Sofroniew MV, Howe CL, Mobley WC
Nerve growth factor signaling, neuroprotection, and neural repair.
Annu Rev Neurosci 24:1217-81 (2001)
Kristiansen M, Ham J
Programmed cell death during neuronal development: the sympathetic neuron model.
Cell Death Differ 21:1025-35 (2014)
Logue SE, Martin SJ
Caspase activation cascades in apoptosis.
Biochem Soc Trans 36:1-9 (2008)
Boivin WA, Cooper DM, Hiebert PR, Granville DJ
Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma.
Lab Invest 89:1195-220 (2009)
Cullen SP, Brunet M, Martin SJ
Granzymes in cancer and immunity.
Cell Death Differ 17:616-23 (2010)
dro04010  MAPK signaling pathway
dro04020  Calcium signaling pathway
dro04064  NF-kappa B signaling pathway
dro04115  p53 signaling pathway
dro04141  Protein processing in endoplasmic reticulum
dro04151  PI3K-Akt signaling pathway
dro04650  Natural killer cell mediated cytotoxicity
dro04668  TNF signaling pathway
KO pathway

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