KEGG   PATHWAY: mcoc04210
Entry
mcoc04210                   Pathway                                
Name
Apoptosis - Mastomys coucha (southern multimammate 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
mcoc04210  Apoptosis
mcoc04210

Other DBs
GO: 0006915
Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116067982  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116067986  Ptpn13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
116068107  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
116068295  Hrk; activator of apoptosis harakiri [KO:K02512]
116068395  Diablo; diablo homolog, mitochondrial isoform X1 [KO:K10522]
116068700  Actb; actin, cytoplasmic 1 [KO:K05692]
116069014  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
116069240  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
116069491  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116070032  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
116070043  Nol3; nucleolar protein 3 isoform X1 [KO:K28177]
116070785  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
116072202  Bcl2a1; bcl-2-related protein A1 [KO:K02162]
116072766  [KO:K16060]
116072810  [KO:K16060]
116072927  Ctsh; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
116072972  Parp3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
116073222  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
116073421  [KO:K04741] [EC:3.4.22.-]
116073648  Mapk6; mitogen-activated protein kinase 6 [KO:K04371] [EC:2.7.11.24]
116073764  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116073929  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116074547  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
116074683  Prf1; perforin-1 [KO:K07818]
116075029  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
116075120  Daxx; death domain-associated protein 6 [KO:K02308]
116075536  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116075741  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
116075788  Lmnb2; lamin-B2 isoform X1 [KO:K07611]
116075868  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
116076013  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
116076129  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
116076417  Ddit3; DNA damage-inducible transcript 3 protein [KO:K04452]
116076765  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116076830  Ern1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
116077116  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
116078189  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
116078335  [KO:K04737]
116078576  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
116078664  [KO:K04736]
116078777  Actg1; actin, cytoplasmic 2 [KO:K05692]
116078954  Septin4; septin-4 isoform X1 [KO:K16943]
116079101  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
116079161  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
116079779  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116080060  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
116080318  Aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
116080443  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
116080518  Fos; proto-oncogene c-Fos [KO:K04379]
116081743  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
116081960  [KO:K01365] [EC:3.4.22.15]
116082097  [KO:K01365] [EC:3.4.22.15]
116082227  [KO:K01365] [EC:3.4.22.15]
116082509  Csf2rb; cytokine receptor common subunit beta [KO:K04738]
116082569  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
116082583  Tubal3; tubulin alpha chain-like 3 [KO:K07374]
116083721  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116084385  [KO:K01353] [EC:3.4.21.79]
116084470  [KO:K01353] [EC:3.4.21.79]
116084677  [KO:K01353] [EC:3.4.21.79]
116084931  [KO:K04722]
116085061  Parp2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
116085105  Parp4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
116085336  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116085396  Ctsb; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
116085641  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116086280  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
116087182  Lmnb1; lamin-B1 isoform X1 [KO:K07611]
116087283  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
116088466  Cflar; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
116088467  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
116088942  [KO:K07374]
116089826  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116089929  Sptan1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
116089938  Endog; endonuclease G, mitochondrial [KO:K01173]
116090053  Traf1; TNF receptor-associated factor 1 [KO:K03172]
116090069  Dab2ip; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
116090342  [KO:K08738]
116090896  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
116091179  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
116091501  Ctsz; cathepsin Z [KO:K08568] [EC:3.4.18.1]
116093027  Ctso; cathepsin O [KO:K01374] [EC:3.4.22.42]
116093096  [KO:K03176] [EC:2.7.10.1]
116093130  Lmna; lamin isoform X1 [KO:K12641]
116093414  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
116093415  Ctss; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
116093420  Mcl1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
116093520  Ngf; beta-nerve growth factor isoform X1 [KO:K02582]
116093530  Nras; GTPase NRas [KO:K07828]
116093781  Casp6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
116093825  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116094433  [KO:K03176] [EC:2.7.10.1]
116095017  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
116095058  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116096245  Jun; transcription factor AP-1 [KO:K04448]
116096465  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
116096967  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
116097025  Dffa; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
116097037  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116097105  Dffb; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
116097315  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
116097922  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
116098456  [KO:K07374]
116098811  Casp2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
116098897  [KO:K08738]
116099018  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116099053  Eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
116099123  Htra2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
116099290  [KO:K05692]
116099362  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116099433  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116099518  Bid; BH3-interacting domain death agonist isoform X1 [KO:K04726]
116099526  Tuba8; tubulin alpha-8 chain [KO:K07374]
116099610  [KO:K07374]
116099614  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
116099791  Kras; GTPase KRas isoform X1 [KO:K07827]
116099794  [KO:K07374]
116099798  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116101682  Bbc3; bcl-2-binding component 3 isoform X1 [KO:K10132]
116101889  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116102201  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
116102536  Ctsc; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
116102969  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116103221  Pidd1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
116103240  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
116103283  Fadd; FAS-associated death domain protein [KO:K02373]
116103352  Ctsf; cathepsin F [KO:K01373] [EC:3.4.22.41]
116103390  Ctsw; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
116103403  Rela; transcription factor p65 isoform X1 [KO:K04735]
116103425  Capn1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
116103467  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
116103761  Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
116103881  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116104023  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
116104026  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116104574  [KO:K04397] [EC:3.4.22.60]
116104693  Parp1; poly [ADP-ribose] polymerase 1 [KO:K24070]
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
Reference
PMID:36652128
  Authors
Liu K, Lan D, Li C, Liu S, Dai X, Song T, Wang X, Kong Q, He Z, Tan J, Zhang J
  Title
A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.
  Journal
Apoptosis 28:313-325 (2023)
DOI:10.1007/s10495-022-01802-4
Related
pathway
mcoc04010  MAPK signaling pathway
mcoc04020  Calcium signaling pathway
mcoc04064  NF-kappa B signaling pathway
mcoc04115  p53 signaling pathway
mcoc04141  Protein processing in endoplasmic reticulum
mcoc04151  PI3K-Akt signaling pathway
mcoc04650  Natural killer cell mediated cytotoxicity
mcoc04668  TNF signaling pathway
KO pathway
ko04210   

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