KEGG   PATHWAY: rtp04210
Entry
rtp04210                    Pathway                                
Name
Apoptosis - Rhincodon typus (whale shark)
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
rtp04210  Apoptosis
rtp04210

Other DBs
GO: 0006915
Organism
Rhincodon typus (whale shark) [GN:rtp]
Gene
109938453  tumor necrosis factor ligand superfamily member 10-like isoform X1 [KO:K04721]
109930946  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
109930951  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
109929457  tumor necrosis factor receptor superfamily member 6-like isoform X1 [KO:K04390]
109916874  fadd; protein FADD [KO:K02373]
109910851  tumor necrosis factor-like [KO:K03156]
109910853  tumor necrosis factor-like [KO:K03156]
109916901  lymphotoxin-alpha-like [KO:K03156]
125488288  tumor necrosis factor-like [KO:K03156]
109910852  tumor necrosis factor-like [KO:K03156]
109929742  CASP8 and FADD-like apoptosis regulator [KO:K04724]
109929740  caspase-8-like [KO:K04398] [EC:3.4.22.61]
109921991  caspase-6-like isoform X1 [KO:K04396] [EC:3.4.22.59]
109923449  caspase-3-like isoform X1 [KO:K04397] [EC:3.4.22.60]
109929106  casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
109918844  zgc:153993; apoptosis regulator BAX [KO:K02159]
109917897  bcl-2 homologous antagonist/killer-like [KO:K14021]
109911651  bcl-2 homologous antagonist/killer isoform X3 [KO:K14021]
109931609  diablo IAP-binding mitochondrial protein isoform X1 [KO:K10522]
109910711  cytochrome c [KO:K08738]
109932546  cytochrome c, somatic [KO:K08738]
109932240  apaf1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
109927787  casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
109924013  LOW QUALITY PROTEIN: perforin-1 [KO:K07818]
125488105  perforin-1-like [KO:K07818]
125482422  LOW QUALITY PROTEIN: perforin-1-like [KO:K07818]
109936906  tubulin alpha chain-like [KO:K07374]
109936908  tubulin alpha-1D chain [KO:K07374]
109924346  tubulin alpha-1C chain isoform X1 [KO:K07374]
109925445  tubulin alpha chain [KO:K07374]
109921125  tubulin alpha-1B chain-like [KO:K07374]
125480938  tubulin alpha-1D chain-like [KO:K07374]
109936907  tubulin alpha-4A chain-like [KO:K07374]
109924431  tubulin alpha chain-like [KO:K07374]
109919235  tubulin alpha-1B chain-like isoform X1 [KO:K07374]
109938200  tubulin alpha-3 chain-like [KO:K07374]
109938199  tubulin alpha-3 chain-like [KO:K07374]
109924282  induced myeloid leukemia cell differentiation protein Mcl-1-like [KO:K02539]
109911698  actin, cytoplasmic type 5 [KO:K05692]
109920530  actin, cytoplasmic 1 [KO:K05692]
109925500  actin-3-like [KO:K05692]
109915807  actin, cytoplasmic type 5-like [KO:K05692]
109933704  sptan1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
109913313  lamin-L(III)-like [KO:K12641]
109927362  lamin-B1-like [KO:K07611]
109915312  lmnb2; lamin-B2 [KO:K07611]
109920100  parp3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
109936796  dffa; DNA fragmentation factor subunit alpha [KO:K02310]
109927312  dffb; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
125486391  endonuclease G, mitochondrial-like [KO:K01173]
109931829  aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
109910482  ern2; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
109922055  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
109916783  traf2b; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
109936083  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
109914380  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
109928820  eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
109933548  eif2s1b; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
109919490  atf4a; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109925170  cathepsin B [KO:K01363] [EC:3.4.22.1]
109925695  cathepsin D-like [KO:K01379] [EC:3.4.23.5]
109913218  ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
109934550  ctsh; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
109919200  procathepsin L-like [KO:K01371] [EC:3.4.22.38]
109926453  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
109919201  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
109921459  ctsl.1; cathepsin L.1 [KO:K01365] [EC:3.4.22.15]
109923998  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
109927260  ctsla; cathepsin La isoform X1 [KO:K01365] [EC:3.4.22.15]
109930144  procathepsin L-like isoform X3 [KO:K01365] [EC:3.4.22.15]
109930146  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
109923996  cathepsin Z-like isoform X1 [KO:K08568] [EC:3.4.18.1]
109937610  LOW QUALITY PROTEIN: cathepsin Z-like [KO:K08568] [EC:3.4.18.1]
125481585  inhibitor of apoptosis protein-like [KO:K16060]
109919537  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
109938723  birc5a; baculoviral IAP repeat-containing protein 5a [KO:K08731]
109930204  apoptosis regulator Bcl-2-like isoform X2 [KO:K02161]
109938698  death domain-associated protein 6-like isoform X1 [KO:K02308]
109931682  ripk1l; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
109932198  dab2ipb; DAB2 interacting protein b isoform X1 [KO:K19901]
109927876  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109917844  mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
109917855  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109925743  jun; transcription factor AP-1 [KO:K04448]
109925076  protein c-Fos-like [KO:K04379]
109910938  map3k14a; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
109918795  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
109927975  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
109916828  NF-kappa-B inhibitor alpha-like [KO:K04734]
109913166  nfkbiab; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha b [KO:K04734]
109918515  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109933624  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109926854  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109912678  growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402]
109912223  traf1; TNF receptor-associated factor 1 [KO:K03172]
109921963  bcl-2-related protein A1-like [KO:K02162]
109934178  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
109912098  pidd1; p53-induced death domain-containing protein 1 [KO:K10130]
109934101  neurotrophin-7-like [KO:K02582]
109915990  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109916739  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
109917303  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X3 [KO:K02649]
109931632  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109916533  akt3a; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109915744  GTPase HRas [KO:K02833]
109919287  GTPase HRas [KO:K07827]
109931543  GTPase KRas isoform X1 [KO:K07827]
109917328  nras; GTPase NRas [KO:K07828]
109911534  raf1b; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
109922810  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
109918415  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
rtp04010  MAPK signaling pathway
rtp04020  Calcium signaling pathway
rtp04115  p53 signaling pathway
rtp04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   
LinkDB

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