KEGG   PATHWAY: zca04210
Entry
zca04210                    Pathway                                
Name
Apoptosis - Zalophus californianus (California sea lion)
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
zca04210  Apoptosis
zca04210

Other DBs
GO: 0006915
Organism
Zalophus californianus (California sea lion) [GN:zca]
Gene
113907841  SEPTIN4; septin-4 isoform X1 [KO:K16943]
113908303  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
113908730  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
113908979  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
113909121  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
113909272  [KO:K01353] [EC:3.4.21.79]
113909565  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
113909591  CASP9; LOW QUALITY PROTEIN: caspase-9 [KO:K04399] [EC:3.4.22.62]
113909627  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
113909653  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
113910017  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113910204  [KO:K01353] [EC:3.4.21.79]
113910226  NFKBIA; NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
113910278  FOS; proto-oncogene c-Fos [KO:K04379]
113910480  BCL2A1; bcl-2-related protein A1 [KO:K02162]
113911261  [KO:K08738]
113911688  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113911860  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
113912320  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
113912489  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
113912631  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
113912803  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
113912971  HRK; activator of apoptosis harakiri [KO:K02512]
113913342  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
113913870  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
113914226  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
113914287  [KO:K16060]
113914288  [KO:K16060]
113914388  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
113914539  BAD; bcl2-associated agonist of cell death [KO:K02158]
113914624  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
113914747  FADD; FAS-associated death domain protein [KO:K02373]
113914802  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
113914876  HRAS; GTPase HRas isoform X1 [KO:K02833]
113914885  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
113914948  RELA; transcription factor p65 [KO:K04735]
113914979  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
113915259  CTSF; LOW QUALITY PROTEIN: cathepsin F [KO:K01373] [EC:3.4.22.41]
113915274  [KO:K04722]
113915477  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
113916244  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
113916366  LMNB2; lamin-B2 isoform X1 [KO:K07611]
113916383  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
113916957  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
113917006  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
113917022  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113917179  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113918169  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
113918633  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
113918898  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113919512  PARP4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
113919983  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
113920559  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
113920561  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
113920876  [KO:K07374]
113921409  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
113921668  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
113921679  PRF1; perforin-1 [KO:K07818]
113921728  TUBAL3; tubulin alpha chain-like 3 isoform X1 [KO:K07374]
113921771  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
113921792  KRAS; GTPase KRas isoform X1 [KO:K07827]
113921804  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
113921922  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
113921928  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
113922015  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
113922091  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
113922330  [KO:K07374]
113922331  [KO:K07374]
113922602  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
113922975  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
113923411  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
113923463  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
113924180  IKBKB; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
113924266  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
113924413  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
113924509  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
113924761  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113924775  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
113925298  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
113925861  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
113925863  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
113926974  [KO:K08738]
113927035  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
113927116  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
113927218  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
113927365  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
113927704  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
113927740  TNF; tumor necrosis factor [KO:K03156]
113928606  [KO:K04736]
113928769  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
113928897  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113929651  LMNB1; lamin-B1 [KO:K07611]
113930311  [KO:K04725] [EC:2.3.2.27]
113930597  [KO:K07210]
113930605  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
113930612  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
113931143  [KO:K07374]
113931151  [KO:K02373]
113931469  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
113931754  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
113931774  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
113931879  NRAS; GTPase NRas [KO:K07828]
113932035  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113932174  LMNA; lamin [KO:K12641]
113932475  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
113932555  [KO:K02539]
113932722  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
113932788  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
113932833  ACTB; actin, cytoplasmic 1 [KO:K05692]
113932864  [KO:K07374]
113933258  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
113933750  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
113934058  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
113934370  [KO:K19901]
113934507  [KO:K01365] [EC:3.4.22.15]
113934602  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
113934717  [KO:K01365] [EC:3.4.22.15]
113934731  [KO:K01365] [EC:3.4.22.15]
113934736  [KO:K01365] [EC:3.4.22.15]
113934914  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
113934934  ENDOG; endonuclease G, mitochondrial [KO:K01173]
113935024  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
113935122  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
113935276  [KO:K07374]
113935537  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113935677  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
113935781  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
113936070  BBC3; bcl-2-binding component 3 [KO:K10132]
113936078  NGF; beta-nerve growth factor [KO:K02582]
113936678  NOL3; nucleolar protein 3 [KO:K28177]
113936867  [KO:K07374]
113936941  HTRA2; LOW QUALITY PROTEIN: serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
113936987  BCL2L1; bcl-2-like protein 1 [KO:K04570]
113937311  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
113937568  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
113937908  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
113938488  [KO:K07374]
113939180  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
113939264  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
113939569  JUN; transcription factor AP-1 [KO:K04448]
113939587  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
113939792  ACTG1; actin, cytoplasmic 2 [KO:K05692]
118355935  [KO:K04741] [EC:3.4.22.-]
118356016  [KO:K02539]
118356158  [KO:K07374]
118356237  [KO:K07374]
118356266  [KO:K07374]
118356554  [KO:K07210]
118357304  [KO:K07374]
118357322  [KO:K07374]
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
zca04010  MAPK signaling pathway
zca04020  Calcium signaling pathway
zca04064  NF-kappa B signaling pathway
zca04115  p53 signaling pathway
zca04141  Protein processing in endoplasmic reticulum
zca04151  PI3K-Akt signaling pathway
zca04650  Natural killer cell mediated cytotoxicity
zca04668  TNF signaling pathway
KO pathway
ko04210   

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