KEGG   PATHWAY: mpah04210
Entry
mpah04210                   Pathway                                
Name
Apoptosis - Mus pahari (shrew mouse)
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
mpah04210  Apoptosis
mpah04210

Other DBs
GO: 0006915
Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110320972  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
110325978  Tnfrsf10b; tumor necrosis factor receptor superfamily member 10B [KO:K04722]
110322215  Faslg; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
110332797  Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
110333124  Fadd; FAS-associated death domain protein [KO:K02373]
110335791  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
110316225  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110337608  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
110321922  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
110321675  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
110320419  Casp6; caspase-6 [KO:K04396] [EC:3.4.22.59]
110336608  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110328167  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
110316901  Bid; BH3-interacting domain death agonist [KO:K04726]
110320030  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
110338169  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
110312863  Diablo; diablo homolog, mitochondrial isoform X1 [KO:K10522]
110332612  Sept4; septin-4 isoform X1 [KO:K16943]
110317283  Htra2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
110332378  cytochrome c-like [KO:K08738]
110316223  cytochrome c, somatic [KO:K08738]
110317786  cytochrome c, testis-specific [KO:K08738]
110326877  Apaf1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
110323338  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
110327029  Prf1; perforin-1 [KO:K07818]
110325862  mast cell protease 8 [KO:K01353] [EC:3.4.21.79]
110325528  granzyme B(G,H) [KO:K01353] [EC:3.4.21.79]
110325544  granzyme C [KO:K01353] [EC:3.4.21.79]
110316306  tubulin alpha-3 chain isoform X1 [KO:K07374]
110321284  Tuba4a; tubulin alpha-4A chain isoform X1 [KO:K07374]
110334563  tubulin alpha-1C chain-like [KO:K07374]
110316395  Tuba8; tubulin alpha-8 chain isoform X1 [KO:K07374]
110316417  tubulin alpha-3 chain isoform X1 [KO:K07374]
110334627  tubulin alpha-1A chain-like [KO:K07374]
110325235  tubulin alpha chain-like [KO:K07374]
110334021  Tubal3; tubulin alpha chain-like 3 [KO:K07374]
110320476  Mcl1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
110331106  Actg1; actin, cytoplasmic 2 [KO:K05692]
110313074  Actb; actin, cytoplasmic 1 [KO:K05692]
110317561  Sptan1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
110319753  Lmna; lamin isoform X1 [KO:K12641]
110333134  Lmnb1; lamin-B1 [KO:K07611]
110326353  Lmnb2; lamin-B2 isoform X1 [KO:K07611]
110322074  Parp1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
110328524  Parp3; poly [ADP-ribose] polymerase 3 isoform X1 [KO:K10798] [EC:2.4.2.30]
110325085  Parp4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
110325405  Parp2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
110323519  Dffa; DNA fragmentation factor subunit alpha [KO:K02310]
110323551  Dffb; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
110337018  DNA fragmentation factor subunit beta-like [KO:K02311] [EC:3.-.-.-]
110318100  Endog; endonuclease G, mitochondrial [KO:K01173]
110313484  Aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
110331346  Ern1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
110318405  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110317210  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110317251  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110338229  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110316020  Capn1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
110321506  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
110327565  caspase-12-like [KO:K04741] [EC:3.4.22.-]
110324429  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
110334651  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110326609  Ddit3; DNA damage-inducible transcript 3 protein [KO:K04452]
110325177  Ctsb; cathepsin B [KO:K01363] [EC:3.4.22.1]
110326827  Ctsc; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
110330411  Ctsd; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
110325287  Ctsf; cathepsin F [KO:K01373] [EC:3.4.22.41]
110327865  Ctsh; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
110320301  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
110333669  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
110315092  cathepsin Q-like [KO:K01365] [EC:3.4.22.15]
110333923  cathepsin 7 [KO:K01365] [EC:3.4.22.15]
110333924  cathepsin 7-like [KO:K01365] [EC:3.4.22.15]
110333975  cathepsin M-like isoform X1 [KO:K01365] [EC:3.4.22.15]
110320655  Ctso; cathepsin O [KO:K01374] [EC:3.4.22.42]
110320470  Ctss; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
110317861  Ctsw; cathepsin W [KO:K08569] [EC:3.4.22.-]
110318622  Ctsz; cathepsin Z [KO:K08568] [EC:3.4.18.1]
110321877  baculoviral IAP repeat-containing protein 2 [KO:K16060]
110327576  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
110328081  baculoviral IAP repeat-containing protein 3 [KO:K16060]
110313538  Xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
110332414  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
110318278  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
110318630  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
110321591  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110335556  Daxx; death domain-associated protein 6 isoform X1 [KO:K02308]
110333762  Ripk1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
110319269  Dab2ip; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
110337870  Map3k5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110326250  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110323252  Jun; transcription factor AP-1 [KO:K04448]
110324365  Fos; proto-oncogene c-Fos isoform X1 [KO:K04379]
110331731  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110339069  Hrk; activator of apoptosis harakiri [KO:K02512]
110332218  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
110334538  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110336182  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110313464  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
110324484  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110319789  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110317041  Rela; transcription factor p65 [KO:K04735]
110330242  Ptpn13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
110316550  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
110326839  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110333844  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110319363  Traf1; TNF receptor-associated factor 1 [KO:K03172]
110327456  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
110323236  Pidd1; p53-induced death domain-containing protein 1 [KO:K10130]
110336584  Bbc3; bcl-2-binding component 3 [KO:K10132]
110333558  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
110316173  Casp2; caspase-2 [KO:K02186] [EC:3.4.22.55]
110320585  Ngf; beta-nerve growth factor [KO:K02582]
110319787  Ntrk1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
110332758  LOW QUALITY PROTEIN: interleukin-3-like [KO:K04736]
110325021  interleukin-3 receptor subunit alpha-like [KO:K04737]
110334519  cytokine receptor common subunit beta-like [KO:K04738]
110334939  cytokine receptor common subunit beta isoform X1 [KO:K04738]
110323448  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110319750  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110327251  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110328811  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110336420  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110322865  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110337888  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
110317258  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110324386  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110322284  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110318967  GTPase HRas-like isoform X1 [KO:K02833]
110319567  Hras; GTPase HRas [KO:K02833]
110338480  GTPase HRas-like [KO:K02833]
110333346  GTPase HRas-like [KO:K02833]
110316221  Kras; GTPase KRas isoform X1 [KO:K07827]
110320340  Nras; GTPase NRas [KO:K07828]
110314893  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110327244  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110326321  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [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
mpah04010  MAPK signaling pathway
mpah04020  Calcium signaling pathway
mpah04064  NF-kappa B signaling pathway
mpah04115  p53 signaling pathway
mpah04141  Protein processing in endoplasmic reticulum
mpah04151  PI3K-Akt signaling pathway
mpah04650  Natural killer cell mediated cytotoxicity
mpah04668  TNF signaling pathway
KO pathway
ko04210   
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