KEGG   PATHWAY: pyu04210
Entry
pyu04210                    Pathway                                
Name
Apoptosis - Herpailurus yagouaroundi (jaguarundi)
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
pyu04210  Apoptosis
pyu04210

Other DBs
GO: 0006915
Organism
Herpailurus yagouaroundi (jaguarundi) [GN:pyu]
Gene
121010280  HRK; activator of apoptosis harakiri [KO:K02512]
121010516  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
121010635  LMNB1; lamin-B1 [KO:K07611]
121010877  IL3; interleukin-3 [KO:K04736]
121011002  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121011268  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
121011444  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121012341  BCL2L1; bcl-2-like protein 1 [KO:K04570]
121012635  [KO:K10798] [EC:2.4.2.-]
121012848  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
121013412  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
121013741  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
121014135  [KO:K01365] [EC:3.4.22.15]
121014161  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
121014190  [KO:K01365] [EC:3.4.22.15]
121014191  [KO:K01365] [EC:3.4.22.15]
121014875  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
121014969  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121015025  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
121015111  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121015149  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070]
121015188  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
121015275  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
121015457  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
121015460  LMNA; lamin [KO:K12641]
121015982  TP53; cellular tumor antigen p53 [KO:K04451]
121016588  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
121017536  ACTB; actin, cytoplasmic 1 [KO:K05692]
121017987  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
121018052  ACTG1; actin, cytoplasmic 2 [KO:K05692]
121018751  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
121019218  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
121019662  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
121019697  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
121019952  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
121020261  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
121020585  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121020589  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
121020751  [KO:K16060]
121020796  [KO:K04741] [EC:3.4.22.-]
121020801  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
121020919  DFFA; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
121021049  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
121021050  CTSS; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
121021051  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
121021391  LMNB2; lamin-B2 [KO:K07611]
121021432  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
121021465  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
121021539  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
121021590  [KO:K07374]
121021909  BID; BH3-interacting domain death agonist [KO:K04726]
121021982  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
121022084  TUBA8; tubulin alpha-8 chain [KO:K07374]
121022226  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121022312  TNF; tumor necrosis factor [KO:K03156]
121022826  HRAS; GTPase HRas isoform X1 [KO:K02833]
121022828  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
121023018  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121023867  FADD; FAS-associated death domain protein [KO:K02373]
121023931  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
121023933  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
121023947  BAD; bcl2-associated agonist of cell death [KO:K02158]
121023950  [KO:K04722]
121023959  RELA; transcription factor p65 [KO:K04735]
121023963  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
121023992  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
121024295  [KO:K01365] [EC:3.4.22.15]
121024375  [KO:K10132]
121025049  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
121025478  [KO:K04725] [EC:2.3.2.27]
121025587  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
121026230  DIABLO; diablo homolog, mitochondrial [KO:K10522]
121026251  [KO:K01365] [EC:3.4.22.15]
121026350  [KO:K01365] [EC:3.4.22.15]
121026362  [KO:K01365] [EC:3.4.22.15]
121027009  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
121027050  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
121027214  JUN; transcription factor AP-1 [KO:K04448]
121027286  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
121027738  NRAS; GTPase NRas [KO:K07828]
121027749  NGF; beta-nerve growth factor [KO:K02582]
121028126  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
121028175  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
121028606  [KO:K08738]
121029283  DAXX; death domain-associated protein 6 [KO:K02308]
121029294  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
121029298  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
121030343  [KO:K08738]
121030906  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
121030907  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
121030909  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
121031081  PLA2G12A; group XIIA secretory phospholipase A2 isoform X1 [KO:K04396] [EC:3.4.22.59]
121031099  TUBA4A; tubulin alpha-4A chain [KO:K07374]
121031398  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
121031586  [KO:K01353] [EC:3.4.21.79]
121031587  [KO:K01353] [EC:3.4.21.79]
121031656  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
121031875  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
121031936  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
121032071  FOS; proto-oncogene c-Fos [KO:K04379]
121032358  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121032687  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
121032861  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
121033000  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
121033019  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
121033733  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
121033998  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
121034013  [KO:K08738]
121034018  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121034366  ENDOG; endonuclease G, mitochondrial [KO:K01173]
121034913  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
121034919  [KO:K08738]
121034931  [KO:K19901]
121035070  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
121035348  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
121036746  PRF1; perforin-1 isoform X1 [KO:K07818]
121036923  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
121037105  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
121037247  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
121038622  [KO:K07374]
121038623  [KO:K07374]
121038624  [KO:K07374]
121038795  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
121038809  KRAS; GTPase KRas isoform X1 [KO:K07827]
121039392  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
121039672  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
121040318  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
121040402  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
121040562  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
121040880  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
121041241  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121041326  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
121041863  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
121042262  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
121042273  BCL2A1; bcl-2-related protein A1 [KO:K02162]
121044434  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
121044477  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
121044717  SEPTIN4; septin-4 isoform X1 [KO:K16943]
121045129  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
121045448  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
121045449  NOL3; nucleolar protein 3 isoform X1 [KO:K28177]
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
pyu04010  MAPK signaling pathway
pyu04020  Calcium signaling pathway
pyu04064  NF-kappa B signaling pathway
pyu04115  p53 signaling pathway
pyu04141  Protein processing in endoplasmic reticulum
pyu04151  PI3K-Akt signaling pathway
pyu04650  Natural killer cell mediated cytotoxicity
pyu04668  TNF signaling pathway
KO pathway
ko04210   

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