KEGG   PATHWAY: dsp04210
Entry
dsp04210                    Pathway                                
Name
Apoptosis - Dipodomys spectabilis (banner-tailed kangaroo 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
dsp04210  Apoptosis
dsp04210

Other DBs
GO: 0006915
Organism
Dipodomys spectabilis (banner-tailed kangaroo rat) [GN:dsp]
Gene
122095011  Hras; GTPase HRas isoform X1 [KO:K02833]
122095294  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122095844  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122095975  [KO:K07374]
122095976  [KO:K07374]
122096287  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122096420  Cflar; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
122096450  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
122096602  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
122097005  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
122097416  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122097796  Ptpn13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
122097824  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122097825  Ctso; cathepsin O [KO:K01374] [EC:3.4.22.42]
122097907  [KO:K08731]
122098053  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
122098513  Diablo; diablo homolog, mitochondrial isoform X1 [KO:K10522]
122098841  Kras; GTPase KRas isoform X1 [KO:K07827]
122098998  Hrk; activator of apoptosis harakiri [KO:K02512]
122099125  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
122099292  Lmnb2; lamin-B2 [KO:K07611]
122099301  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122099331  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122099409  Actg1; actin, cytoplasmic 2 [KO:K05692]
122099715  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
122099877  Fadd; FAS-associated death domain protein [KO:K02373]
122100440  Tp53; cellular tumor antigen p53 [KO:K04451]
122100872  Pik3r2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122100994  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
122101263  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122101664  Bid; BH3-interacting domain death agonist isoform X1 [KO:K04726]
122101672  Tuba8; LOW QUALITY PROTEIN: tubulin alpha-8 chain [KO:K07374]
122102049  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
122102541  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
122102575  Pidd1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
122103419  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
122103807  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
122103907  Lmnb1; lamin-B1 [KO:K07611]
122104319  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122104746  Ctsf; cathepsin F [KO:K01373] [EC:3.4.22.41]
122104935  Capn1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
122105036  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
122105094  Rela; transcription factor p65 isoform X1 [KO:K04735]
122105345  Ctsw; cathepsin W [KO:K08569] [EC:3.4.22.-]
122105905  Casp2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
122106151  Tuba1b; tubulin alpha-1B chain [KO:K07374]
122106173  [KO:K07374]
122106264  Tuba1c; tubulin alpha-1C chain [KO:K07374]
122106511  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
122107048  [KO:K19901]
122107096  Traf1; TNF receptor-associated factor 1 [KO:K03172]
122107232  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122107277  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
122107361  [KO:K07374]
122107474  Tuba4a; tubulin alpha-4A chain [KO:K07374]
122107663  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
122107826  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122108047  [KO:K02649]
122108136  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
122108407  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
122108925  Endog; endonuclease G, mitochondrial [KO:K01173]
122108926  Sptan1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
122108943  Jun; transcription factor AP-1 [KO:K04448]
122109350  Lmna; lamin [KO:K12641]
122109365  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
122109432  Ctss; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
122109658  Ntrk1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
122109719  Mcl1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
122109759  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
122109926  [KO:K04725] [EC:2.3.2.27]
122109936  Aifm1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
122110260  Atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
122110391  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
122110854  [KO:K08738]
122111128  Bak1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
122111281  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
122111402  Daxx; death domain-associated protein 6 isoform X1 [KO:K02308]
122111510  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
122112157  [KO:K01365] [EC:3.4.22.15]
122112201  [KO:K08738]
122112600  Parp4; protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.-]
122113137  [KO:K07374]
122113471  [KO:K01353] [EC:3.4.21.79]
122113474  [KO:K01353] [EC:3.4.21.79]
122113601  Actb; actin, cytoplasmic 1 [KO:K05692]
122113644  [KO:K01365] [EC:3.4.22.15]
122113654  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122113659  [KO:K01365] [EC:3.4.22.15]
122113774  [KO:K01365] [EC:3.4.22.15]
122113775  [KO:K01365] [EC:3.4.22.15]
122113776  [KO:K01365] [EC:3.4.22.15]
122113777  [KO:K01365] [EC:3.4.22.15]
122113778  [KO:K01365] [EC:3.4.22.15]
122113780  [KO:K01365] [EC:3.4.22.15]
122114391  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122114582  Ctsc; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
122114887  [KO:K01365] [EC:3.4.22.15]
122115021  [KO:K08738]
122115378  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122115398  Il3; interleukin-3 [KO:K04736]
122115917  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
122115995  Casp7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
122116005  Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
122116492  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122116859  Eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
122116980  [KO:K08738]
122117286  [KO:K08738]
122117343  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122117971  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
122118367  Nras; GTPase NRas [KO:K07828]
122118375  Ngf; beta-nerve growth factor [KO:K02582]
122118881  Fos; proto-oncogene c-Fos [KO:K04379]
122118920  Septin4; septin-4 isoform X1 [KO:K16943]
122119240  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
122119299  Csf2rb; cytokine receptor common subunit beta isoform X1 [KO:K04738]
122119434  Bcl2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
122120267  Bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
122121284  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
122121487  Dffa; DNA fragmentation factor subunit alpha [KO:K02310]
122121501  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122122303  Prf1; perforin-1 [KO:K07818]
122123339  [KO:K00922] [EC:2.7.1.153]
122123374  Bcl2a1; bcl-2-related protein A1 [KO:K02162]
122123430  Ctsh; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
122123517  [KO:K04722]
122123666  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
122123899  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
122124058  Ddit3; DNA damage-inducible transcript 3 protein [KO:K04452]
122124195  [KO:K08738]
122124613  Ctsz; cathepsin Z [KO:K08568] [EC:3.4.18.1]
122125215  Htra2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
122125257  Ctsb; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
122125754  Bbc3; bcl-2-binding component 3 isoform X1 [KO:K10132]
122125840  Bax; apoptosis regulator BAX [KO:K02159]
122126104  Casp3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
122126135  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
122126138  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
122126229  Nol3; nucleolar protein 3 [KO:K28177]
122126604  Parp2; poly [ADP-ribose] polymerase 2 [KO:K28005]
122126696  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122126737  Parp1; poly [ADP-ribose] polymerase 1 [KO:K24070]
122127154  Casp6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
122127164  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
122127393  Dffb; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
122128373  Ern1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
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
dsp04010  MAPK signaling pathway
dsp04020  Calcium signaling pathway
dsp04064  NF-kappa B signaling pathway
dsp04115  p53 signaling pathway
dsp04141  Protein processing in endoplasmic reticulum
dsp04151  PI3K-Akt signaling pathway
dsp04650  Natural killer cell mediated cytotoxicity
dsp04668  TNF signaling pathway
KO pathway
ko04210   

DBGET integrated database retrieval system