KEGG   PATHWAY: aju04210
Entry
aju04210                    Pathway                                
Name
Apoptosis - Acinonyx jubatus (cheetah)
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
aju04210  Apoptosis
aju04210

Other DBs
GO: 0006915
Organism
Acinonyx jubatus (cheetah) [GN:aju]
Gene
106990055  tumor necrosis factor ligand superfamily member 10 [KO:K04721]
106982854  tumor necrosis factor receptor superfamily member 10B-like isoform X1 [KO:K04722]
106979842  tumor necrosis factor ligand superfamily member 6 [KO:K04389]
106980953  tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
106982870  FAS-associated death domain protein [KO:K02373]
106983958  tumor necrosis factor [KO:K03156]
106965450  tumor necrosis factor receptor superfamily member 1A [KO:K03158]
106971422  tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
106987988  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
106987995  caspase-8 [KO:K04398] [EC:3.4.22.61]
106987987  caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
106983648  caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
106979326  caspase-3 isoform X3 [KO:K02187] [EC:3.4.22.56]
106974123  caspase-7 [KO:K04397] [EC:3.4.22.60]
106968455  BH3-interacting domain death agonist [KO:K04726]
106988699  apoptosis regulator BAX isoform X1 [KO:K02159]
106976101  bcl-2 homologous antagonist/killer [KO:K14021]
106967598  diablo IAP-binding mitochondrial protein [KO:K10522]
106989946  SEPTIN4; septin-4 isoform X1 [KO:K16943]
113592650  serine/arginine repetitive matrix protein 1 isoform X1 [KO:K16943]
106988577  serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
106973875  cytochrome c-like [KO:K08738]
128316364  cytochrome c-like [KO:K08738]
106982840  cytochrome c [KO:K08738]
106986613  cytochrome c-like [KO:K08738]
106973746  apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
106975594  caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
106967198  perforin-1 [KO:K07818]
106987873  mast cell protease 1A-like isoform X1 [KO:K01353] [EC:3.4.21.79]
106987852  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
128313779  tubulin alpha-3 chain [KO:K07374]
106969282  tubulin alpha-1B chain [KO:K07374]
106969285  tubulin alpha-1C chain isoform X1 [KO:K07374]
106968459  tubulin alpha-8 chain [KO:K07374]
106972801  LOW QUALITY PROTEIN: tubulin alpha-8 chain [KO:K07374]
106983635  tubulin alpha-3 chain [KO:K07374]
106988132  tubulin alpha chain-like 3 isoform X2 [KO:K07374]
106970047  tubulin alpha-4A chain [KO:K07374]
106969284  tubulin alpha-1A chain [KO:K07374]
106986653  induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
106987399  actin, cytoplasmic 2 [KO:K05692]
106984514  actin, cytoplasmic 1 [KO:K05692]
106966268  spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
106981532  lamin [KO:K12641]
106989696  LOW QUALITY PROTEIN: lamin-B2 [KO:K07611]
106970739  lamin-B1 [KO:K07611]
106968624  poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070] [EC:2.4.2.30]
106971396  poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
106979809  protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.30]
106987012  protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
106984923  DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
106975297  DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
106966261  endonuclease G, mitochondrial [KO:K01173]
106981569  apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
106978670  serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
106989490  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
106978946  inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
106968786  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
106976077  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
106971147  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
106983173  calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
106976502  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
106978143  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
106971552  eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
106979942  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
106975861  DNA damage-inducible transcript 3 protein [KO:K04452]
106975817  cathepsin B isoform X3 [KO:K01363] [EC:3.4.22.1]
106967745  dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
106971074  cathepsin D [KO:K01379] [EC:3.4.23.5]
106971117  cathepsin F [KO:K01373] [EC:3.4.22.41]
106988474  pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
106979872  cathepsin K [KO:K01371] [EC:3.4.22.38]
106971460  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
106971464  procathepsin L-like isoform X1 [KO:K01365] [EC:3.4.22.15]
106971491  procathepsin L [KO:K01365] [EC:3.4.22.15]
106971473  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
113596115  procathepsin L-like isoform X2 [KO:K01365] [EC:3.4.22.15]
106971463  procathepsin L [KO:K01365] [EC:3.4.22.15]
113596116  LOW QUALITY PROTEIN: procathepsin L-like [KO:K01365] [EC:3.4.22.15]
106971474  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
106971459  LOW QUALITY PROTEIN: procathepsin L-like [KO:K01365] [EC:3.4.22.15]
106982439  cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
106979853  cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
106971131  cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
106969919  cathepsin Z [KO:K08568] [EC:3.4.18.1]
106976507  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
106976508  baculoviral IAP repeat-containing protein 2 [KO:K16060]
106972832  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
106981916  baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
106976034  bcl-2-like protein 11 isoform X6 [KO:K16341]
106986010  bcl-2-like protein 1 [KO:K04570]
106985187  apoptosis regulator Bcl-2 [KO:K02161]
106976080  death domain-associated protein 6 [KO:K02308]
106976163  receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
106986610  disabled homolog 2-interacting protein isoform X4 [KO:K19901]
106983673  mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
106969894  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
106970668  mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
106989581  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
106981699  bcl2-associated agonist of cell death [KO:K02158]
106974986  transcription factor Jun [KO:K04448]
106974355  protein c-Fos [KO:K04379]
106972437  cellular tumor antigen p53 [KO:K04451]
113595095  activator of apoptosis harakiri [KO:K02512]
106988147  mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
106966935  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
106990012  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
106988817  NF-kappa-B essential modulator isoform X1 [KO:K07210]
106965509  NF-kappa-B inhibitor alpha [KO:K04734]
106984704  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
106971136  transcription factor p65 [KO:K04735]
106970662  tyrosine-protein phosphatase non-receptor type 13 isoform X2 [KO:K02374]
106989693  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
106985200  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
113594268  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
106986638  TNF receptor-associated factor 1 isoform X1 [KO:K03172]
106988491  bcl-2-related protein A1 [KO:K02162]
106983963  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
106988898  p53-induced death domain-containing protein 1 isoform X2 [KO:K10130]
106973568  bcl-2-binding component 3 [KO:K10132]
106978896  phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
106980767  caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
106969645  beta-nerve growth factor isoform X2 [KO:K02582]
106988854  high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
113604567  interleukin-3 [KO:K04736]
113597168  LOW QUALITY PROTEIN: interleukin-3 receptor subunit alpha [KO:K04737]
106981032  cytokine receptor common subunit beta [KO:K04738]
106984896  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106984265  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106973880  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106976917  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
106973297  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
106969150  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
106978772  3-phosphoinositide-dependent protein kinase 1 isoform X5 [KO:K06276] [EC:2.7.11.1]
106979622  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
106975558  RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
106985046  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106987957  GTPase HRas isoform X1 [KO:K02833]
106968778  GTPase KRas isoform X1 [KO:K07827]
106969596  GTPase NRas [KO:K07828]
106977129  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106980282  dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
106975474  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106969232  mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
106990008  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
aju04010  MAPK signaling pathway
aju04020  Calcium signaling pathway
aju04064  NF-kappa B signaling pathway
aju04115  p53 signaling pathway
aju04141  Protein processing in endoplasmic reticulum
aju04151  PI3K-Akt signaling pathway
aju04650  Natural killer cell mediated cytotoxicity
aju04668  TNF signaling pathway
KO pathway
ko04210   
LinkDB

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