KEGG   PATHWAY: mlk04210
Entry
mlk04210                    Pathway                                
Name
Apoptosis - Mustela lutreola (European mink)
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
mlk04210  Apoptosis
mlk04210

Other DBs
GO: 0006915
Organism
Mustela lutreola (European mink) [GN:mlk]
Gene
131824863  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
131817431  tumor necrosis factor receptor superfamily member 1A-like [KO:K04722]
131814928  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
131830067  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
131817074  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
131834372  TNF; tumor necrosis factor isoform X1 [KO:K03156]
131838434  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
131817910  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
131827577  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
131827572  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
131827576  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
131829380  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
131820467  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
131830675  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
131838342  BID; BH3-interacting domain death agonist [KO:K04726]
131817775  BAX; apoptosis regulator BAX [KO:K02159]
131834235  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
131811910  DIABLO; diablo IAP-binding mitochondrial protein isoform X1 [KO:K10522]
131815596  SEPTIN4; septin-4 isoform X1 [KO:K16943]
131815618  uncharacterized protein LOC131815618 [KO:K16943]
131840338  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
131833963  cytochrome c-like [KO:K08738]
131834139  cytochrome c [KO:K08738]
131829521  cytochrome c [KO:K08738]
131839300  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
131809520  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
131828867  PRF1; perforin-1 isoform X1 [KO:K07818]
131836421  granzyme B-like [KO:K01353] [EC:3.4.21.79]
131838055  TUBAL3; LOW QUALITY PROTEIN: tubulin alpha chain-like 3 [KO:K07374]
131838335  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
131838804  tubulin alpha-1B chain isoform X1 [KO:K07374]
131838805  tubulin alpha-1A chain [KO:K07374]
131838806  tubulin alpha-1C chain isoform X1 [KO:K07374]
131811241  tubulin alpha-3 chain-like [KO:K07374]
131819705  tubulin alpha-1B chain-like [KO:K07374]
131827429  tubulin alpha-4A chain [KO:K07374]
131814751  tubulin alpha-8 chain isoform X1 [KO:K07374]
131824412  tubulin alpha-1A chain-like [KO:K07374]
131810812  tubulin alpha-3 chain [KO:K07374]
131809984  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
131820100  ACTB; actin, cytoplasmic 1 [KO:K05692]
131816144  ACTG1; actin, cytoplasmic 2 [KO:K05692]
131812911  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
131815267  LMNA; lamin [KO:K12641]
131823248  LMNB2; lamin-B2 isoform X1 [KO:K07611]
131831983  LMNB1; lamin-B1 [KO:K07611]
131814492  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
131836040  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
131813709  PARP4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.30]
131823987  PARP3; protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
131809654  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
131810298  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
131813022  ENDOG; endonuclease G, mitochondrial [KO:K01173]
131821391  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
131816957  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
131812685  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
131824160  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
131838936  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
131834230  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
131815210  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
131814739  CAPN2; calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
131834806  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
131840420  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
131836705  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
131839499  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
131818296  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
131838557  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
131833738  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
131839471  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
131817810  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
131816073  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
131835486  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
131810361  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
131812148  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
131812454  procathepsin L-like isoform X1 [KO:K01365] [EC:3.4.22.15]
131812673  procathepsin L-like isoform X1 [KO:K01365] [EC:3.4.22.15]
131812746  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
131812843  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
131831685  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
131809393  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
131815706  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
131807378  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
131834540  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
131834551  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
131822235  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
131816466  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
131840447  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
131807889  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
131811845  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
131834240  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
131834461  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
131812908  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
131833762  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
131828723  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
131831160  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
131832665  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
131814653  BAD; bcl2-associated agonist of cell death [KO:K02158]
131809019  JUN; transcription factor Jun [KO:K04448]
131836857  FOS; protein c-Fos [KO:K04379]
131815809  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
131811633  HRK; activator of apoptosis harakiri [KO:K02512]
131817097  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
131828549  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
131820342  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
131822182  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
131836470  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
131829855  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
131815578  RELA; transcription factor p65 [KO:K04735]
131831003  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
131812894  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
131823251  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
131809793  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
131812230  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
131835497  BCL2A1; bcl-2-related protein A1 [KO:K02162]
131835390  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
131817952  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
131818362  BBC3; bcl-2-binding component 3 [KO:K10132]
131811605  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
131829885  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
131810037  NGF; beta-nerve growth factor [KO:K02582]
131814908  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
131831140  interleukin-3-like [KO:K04736]
131821315  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
131839429  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
131809015  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824589  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824847  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
131823754  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
131832309  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
131810162  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
131819765  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
131837056  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
131815063  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131817507  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131818337  HRAS; GTPase HRas isoform X1 [KO:K02833]
131838926  KRAS; GTPase KRas isoform X1 [KO:K07827]
131810307  NRAS; GTPase NRas isoform X1 [KO:K07828]
131810524  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
131824239  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
131835957  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
131823312  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
131811758  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
131820131  MAPK3; 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
mlk04010  MAPK signaling pathway
mlk04020  Calcium signaling pathway
mlk04064  NF-kappa B signaling pathway
mlk04115  p53 signaling pathway
mlk04141  Protein processing in endoplasmic reticulum
mlk04151  PI3K-Akt signaling pathway
mlk04650  Natural killer cell mediated cytotoxicity
mlk04668  TNF signaling pathway
KO pathway
ko04210   
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