KEGG   PATHWAY: anu04210
Entry
anu04210                    Pathway                                
Name
Apoptosis - Arvicanthis niloticus (African grass rat)
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
anu04210  Apoptosis
anu04210

Other DBs
GO: 0006915
Organism
Arvicanthis niloticus (African grass rat) [GN:anu]
Gene
117693421  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117693439  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117693444  Bcl2a1; bcl-2-related protein A1 [KO:K02162]
117693491  Parp3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
117693554  Ctsw; cathepsin W [KO:K08569] [EC:3.4.22.-]
117693791  Ctsh; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
117694154  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
117694841  Aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
117695513  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
117696104  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
117696143  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
117696275  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
117696384  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
117696618  Lmnb2; lamin-B2 [KO:K07611]
117696642  Ddit3; DNA damage-inducible transcript 3 protein [KO:K04452]
117697169  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
117697448  Fos; proto-oncogene c-Fos [KO:K04379]
117697536  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117697774  Hrk; activator of apoptosis harakiri [KO:K02512]
117697924  Actb; actin, cytoplasmic 1 [KO:K05692]
117698251  Diablo; diablo homolog, mitochondrial [KO:K10522]
117699009  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117699494  Atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
117699648  [KO:K04741] [EC:3.4.22.-]
117699737  Ptpn13; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
117699887  [KO:K16060]
117699964  [KO:K16060]
117700217  [KO:K08738]
117700355  Bbc3; bcl-2-binding component 3 isoform X1 [KO:K10132]
117700780  Fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
117701010  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
117701548  [KO:K08738]
117701914  [KO:K04467] [EC:2.7.11.10]
117702594  Sptan1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
117702752  Endog; endonuclease G, mitochondrial [KO:K01173]
117703388  Dab2ip; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
117703456  Ctsz; cathepsin Z [KO:K08568] [EC:3.4.18.1]
117703605  Traf1; TNF receptor-associated factor 1 [KO:K03172]
117703673  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
117703834  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
117704117  [KO:K08738]
117704975  [KO:K04722]
117704983  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
117705037  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
117705316  Ctsb; cathepsin B [KO:K01363] [EC:3.4.22.1]
117705322  Tuba4a; tubulin alpha-4A chain isoform X1 [KO:K07374]
117705784  [KO:K01353] [EC:3.4.21.79]
117705809  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
117705880  [KO:K01353] [EC:3.4.21.79]
117706054  Parp4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
117706123  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
117706352  Parp2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
117706557  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
117706566  Ngf; beta-nerve growth factor [KO:K02582]
117706623  Lmna; lamin [KO:K12641]
117706636  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117706649  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
117706664  Hras; GTPase HRas isoform X1 [KO:K02833]
117706908  Mcl1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
117706966  Nras; GTPase NRas [KO:K07828]
117707042  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
117707211  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
117707235  Ntrk1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
117707492  Ctss; cathepsin S [KO:K01368] [EC:3.4.22.27]
117707493  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
117707831  Ctso; cathepsin O [KO:K01374] [EC:3.4.22.42]
117707901  Casp6; caspase-6 [KO:K04396] [EC:3.4.22.59]
117708552  Capn1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
117708916  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
117708961  [KO:K02649]
117708986  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
117709048  Pidd1; p53-induced death domain-containing protein 1 [KO:K10130]
117709069  Jun; transcription factor AP-1 [KO:K04448]
117709255  Dffa; DNA fragmentation factor subunit alpha [KO:K02310]
117709591  Dffb; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
117709966  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
117710000  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
117710030  Fadd; FAS-associated death domain protein [KO:K02373]
117710315  [KO:K04736]
117710574  Tp53; cellular tumor antigen p53 [KO:K04451]
117710587  Septin4; septin-4 isoform X1 [KO:K16943]
117710754  Ern1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
117710865  Actg1; actin, cytoplasmic 2 [KO:K05692]
117710914  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
117711130  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
117711275  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
117712095  [KO:K07374]
117712831  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
117713452  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
117713706  Ripk1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
117713897  Ctsv; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
117714111  Tubal3; tubulin alpha chain-like 3 [KO:K07374]
117714720  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
117714743  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
117714897  [KO:K07374]
117714902  Kras; GTPase KRas isoform X1 [KO:K07827]
117714946  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
117714960  [KO:K07374]
117715120  Tuba8; tubulin alpha-8 chain [KO:K07374]
117715167  Bid; BH3-interacting domain death agonist [KO:K04726]
117715254  Eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
117715331  Htra2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
117715476  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
117715599  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
117716348  Bcl2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
117716367  Faslg; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
117716491  [KO:K04737]
117716580  Ctsc; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
117717119  [KO:K08738]
117717335  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
117717711  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117718493  Tuba1a; tubulin alpha-1A chain [KO:K07374]
117718494  Tuba1b; tubulin alpha-1B chain [KO:K07374]
117718519  [KO:K07374]
117718898  [KO:K04738]
117719059  [KO:K04738]
117719125  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117719540  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
117719592  Lmnb1; lamin-B1 [KO:K07611]
117720836  [KO:K08738]
117720880  Casp2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
117721391  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
117721481  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117721518  Parp1; poly [ADP-ribose] polymerase 1 [KO:K24070]
117721547  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
117721973  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
117721984  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
117722249  Bax; apoptosis regulator BAX isoform X1 [KO:K02159]
117722582  Rela; transcription factor p65 [KO:K04735]
117722978  Ctsf; cathepsin F [KO:K01373] [EC:3.4.22.41]
117723297  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
117723299  Nol3; nucleolar protein 3 isoform X1 [KO:K28177]
117723761  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117724336  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
117724473  Daxx; death domain-associated protein 6 isoform X1 [KO:K02308]
117724492  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
117724681  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
117724847  Prf1; perforin-1 [KO:K07818]
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
anu04010  MAPK signaling pathway
anu04020  Calcium signaling pathway
anu04064  NF-kappa B signaling pathway
anu04115  p53 signaling pathway
anu04141  Protein processing in endoplasmic reticulum
anu04151  PI3K-Akt signaling pathway
anu04650  Natural killer cell mediated cytotoxicity
anu04668  TNF signaling pathway
KO pathway
ko04210   

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