KEGG   PATHWAY: llv04210
Entry
llv04210                    Pathway                                
Name
Apoptosis - Lutra lutra (Eurasian river otter)
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
llv04210  Apoptosis
llv04210

Other DBs
GO: 0006915
Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125100439  tumor necrosis factor ligand superfamily member 10-like [KO:K04721]
125086282  tumor necrosis factor ligand superfamily member 6 [KO:K04389]
125084890  tumor necrosis factor receptor superfamily member 6-like [KO:K04390]
125079328  FAS-associated death domain protein-like [KO:K02373]
125103142  tumor necrosis factor isoform X1 [KO:K03156]
125107758  tumor necrosis factor receptor superfamily member 1A-like isoform X1 [KO:K03158]
125088780  tumor necrosis factor receptor type 1-associated DEATH domain protein-like [KO:K03171]
125095000  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
125094998  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
125094997  LOW QUALITY PROTEIN: caspase-10-like [KO:K04400] [EC:3.4.22.63]
125093276  caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
125091274  caspase-3 [KO:K02187] [EC:3.4.22.56]
125084583  caspase-7 [KO:K04397] [EC:3.4.22.60]
125106056  BH3-interacting domain death agonist-like [KO:K04726]
125086017  apoptosis regulator BAX-like [KO:K02159]
125089829  apoptosis regulator BAX [KO:K02159]
125102734  bcl-2 homologous antagonist/killer [KO:K14021]
125082204  diablo IAP-binding mitochondrial protein isoform X1 [KO:K10522]
125087042  uncharacterized protein LOC125087042 isoform X1 [KO:K16943]
125108306  serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
125109865  LOW QUALITY PROTEIN: cytochrome c homolog [KO:K08738]
125080891  cytochrome c [KO:K08738]
125082666  cytochrome c-like [KO:K08738]
125106261  apoptotic protease-activating factor 1 [KO:K02084]
125098709  caspase-9-like isoform X1 [KO:K04399] [EC:3.4.22.62]
125084642  perforin-1-like isoform X1 [KO:K07818]
125104493  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
125104667  granzyme B-like [KO:K01353] [EC:3.4.21.79]
125085593  LOW QUALITY PROTEIN: tubulin alpha chain-like [KO:K07374]
125086043  tubulin alpha-8 chain-like [KO:K07374]
125094690  tubulin alpha-1C chain-like [KO:K07374]
125095116  tubulin alpha-4A chain-like [KO:K07374]
125095140  tubulin alpha-4A chain [KO:K07374]
125096476  tubulin alpha-1C chain-like [KO:K07374]
125088530  tubulin alpha chain-like [KO:K07374]
125097294  tubulin alpha-8 chain-like [KO:K07374]
125106192  tubulin alpha-1A chain [KO:K07374]
125106193  tubulin alpha-1C chain [KO:K07374]
125081884  tubulin alpha-3 chain [KO:K07374]
125081976  tubulin alpha-3 chain-like isoform X1 [KO:K07374]
125106546  LOW QUALITY PROTEIN: tubulin alpha chain-like 3 [KO:K07374]
125106792  tubulin alpha-8 chain isoform X1 [KO:K07374]
125107228  tubulin alpha-1B chain [KO:K07374]
125097752  induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
125092924  actin, cytoplasmic 2-like [KO:K05692]
125093566  actin, cytoplasmic 2-like [KO:K05692]
125102727  actin, cytoplasmic 2-like [KO:K05692]
125087003  actin, cytoplasmic 2 [KO:K05692]
125090635  actin, cytoplasmic 1 [KO:K05692]
125084102  spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
125086167  prelamin-A/C [KO:K12641]
125100263  lamin-B1 [KO:K07611]
125087180  lamin-B2 [KO:K07611]
125085856  poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
125079322  protein mono-ADP-ribosyltransferase PARP3-like [KO:K10798] [EC:2.4.2.30]
125095928  LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 2-like [KO:K10798] [EC:2.4.2.30]
125096140  protein mono-ADP-ribosyltransferase PARP4-like isoform X1 [KO:K10798] [EC:2.4.2.30]
125105383  poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
125096813  DNA fragmentation factor subunit alpha-like [KO:K02310]
125096988  DNA fragmentation factor subunit beta-like [KO:K02311] [EC:3.-.-.-]
125082840  endonuclease G, mitochondrial isoform X1 [KO:K01173]
125091848  apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
125086988  serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
125083298  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
125109360  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125107116  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125103123  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
125083453  LOW QUALITY PROTEIN: calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
125078527  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
125085781  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
125078536  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
125108962  eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
125105209  eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
125106338  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125106097  DNA damage-inducible transcript 3 protein [KO:K04452]
125092926  cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
125078452  dipeptidyl peptidase 1-like isoform X1 [KO:K01275] [EC:3.4.14.1]
125078652  cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
125079566  cathepsin F-like isoform X1 [KO:K01373] [EC:3.4.22.41]
125103910  pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
125096877  cathepsin K [KO:K01371] [EC:3.4.22.38]
125083577  LOW QUALITY PROTEIN: procathepsin L-like [KO:K01365] [EC:3.4.22.15]
125083642  procathepsin L-like isoform X1 [KO:K01365] [EC:3.4.22.15]
125083644  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
125083645  procathepsin L-like isoform X1 [KO:K01365] [EC:3.4.22.15]
125083647  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
125093107  cathepsin O-like [KO:K01374] [EC:3.4.22.42]
125096876  cathepsin S [KO:K01368] [EC:3.4.22.27]
125078997  cathepsin W-like isoform X1 [KO:K08569] [EC:3.4.22.-]
125108691  cathepsin Z [KO:K08568] [EC:3.4.18.1]
125079331  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2-like [KO:K16060]
125079332  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
125091577  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
125086892  baculoviral IAP repeat-containing protein 5 [KO:K08731]
125108514  bcl-2-like protein 11 isoform X1 [KO:K16341]
125108270  bcl-2-like protein 1 [KO:K04570]
125081686  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
125102313  death domain-associated protein 6 isoform X1 [KO:K02308]
125103136  receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
125083234  disabled homolog 2-interacting protein isoform X1 [KO:K19901]
125103005  mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
125099732  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125084526  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125093137  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125079150  bcl2-associated agonist of cell death-like isoform X1 [KO:K02158]
125098159  transcription factor Jun [KO:K04448]
125105343  protein c-Fos [KO:K04379]
125087037  cellular tumor antigen p53 isoform X1 [KO:K04451]
125082168  activator of apoptosis harakiri [KO:K02512]
125086838  mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
125084339  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
125094028  inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
125091312  NF-kappa-B essential modulator isoform X1 [KO:K07210]
125105211  NF-kappa-B inhibitor alpha [KO:K04734]
125093224  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
125078405  transcription factor p65 isoform X1 [KO:K04735]
125093135  tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
125084011  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
125087160  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
125098822  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
125083470  TNF receptor-associated factor 1 [KO:K03172]
125105668  bcl-2-related protein A1-like [KO:K02162]
125078433  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
125078241  p53-induced death domain-containing protein 1-like isoform X1 [KO:K10130]
125089753  bcl-2-binding component 3, isoforms 1/2 isoform X1 [KO:K10132]
125082638  phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
125080608  caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
125099036  beta-nerve growth factor [KO:K02582]
125085737  high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
125091940  interleukin-3 receptor subunit alpha-like isoform X1 [KO:K04737]
125106754  LOW QUALITY PROTEIN: cytokine receptor common subunit beta-like [KO:K04738]
125100627  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125103868  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
125096824  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125099801  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125082268  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125097558  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
125090410  3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
125086439  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125104283  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125089561  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125078621  GTPase HRas isoform X1 [KO:K02833]
125106241  GTPase KRas isoform X1 [KO:K07827]
125098043  GTPase NRas [KO:K07828]
125108469  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125105594  dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125086704  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125081690  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125090203  mitogen-activated protein kinase 3 [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
llv04010  MAPK signaling pathway
llv04020  Calcium signaling pathway
llv04064  NF-kappa B signaling pathway
llv04115  p53 signaling pathway
llv04141  Protein processing in endoplasmic reticulum
llv04151  PI3K-Akt signaling pathway
llv04650  Natural killer cell mediated cytotoxicity
llv04668  TNF signaling pathway
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system