KEGG   PATHWAY: psiu04210
Entry
psiu04210                   Pathway                                
Name
Apoptosis - Phocoena sinus (vaquita)
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
psiu04210  Apoptosis
psiu04210

Other DBs
GO: 0006915
Organism
Phocoena sinus (vaquita) [GN:psiu]
Gene
116753080  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
116756118  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
116756119  tumor necrosis factor receptor superfamily member 10B-like isoform X1 [KO:K04722]
116739025  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
116741753  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
116757390  FADD; FAS-associated death domain protein [KO:K02373]
116762489  TNF; tumor necrosis factor [KO:K03156]
116760562  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
116756986  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
116757029  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
116756541  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
116754615  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
116746660  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
116742039  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
116761091  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
116744670  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
116762061  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
116739045  DIABLO; diablo homolog, mitochondrial [KO:K10522]
116745342  SEPTIN4; septin-4 isoform X1 [KO:K16943]
116764730  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
116752884  cytochrome c-like [KO:K08738]
116759632  cytochrome c [KO:K08738]
116762684  cytochrome c-like [KO:K08738]
116749491  cytochrome c-like [KO:K08738]
116756700  cytochrome c 2 [KO:K08738]
116752326  cytochrome c [KO:K08738]
116760585  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
116757481  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
116742030  PRF1; perforin-1 [KO:K07818]
116748601  LOW QUALITY PROTEIN: mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
116749064  granzyme B-like isoform X1 [KO:K01353] [EC:3.4.21.79]
116760136  TUBA8; tubulin alpha-8 chain [KO:K07374]
116760287  tubulin alpha-1B chain [KO:K07374]
116760704  TUBA1A; tubulin alpha-1A chain isoform X1 [KO:K07374]
116760705  tubulin alpha-1C chain-like [KO:K07374]
116739344  tubulin alpha-3 chain-like [KO:K07374]
116748527  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
116756906  tubulin alpha-1D chain-like isoform X1 [KO:K07374]
116757159  tubulin alpha-4A chain [KO:K07374]
116765082  tubulin alpha-3 chain [KO:K07374]
116760285  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
116739532  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
116745324  ACTG1; actin, cytoplasmic 2 [KO:K05692]
116755716  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
116757199  LMNA; lamin isoform X1 [KO:K12641]
116750548  LMNB2; lamin-B2 [KO:K07611]
116751708  LMNB1; LOW QUALITY PROTEIN: lamin-B1 [KO:K07611]
116757570  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
116762117  PARP3; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
116749776  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
116742403  DFFA; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
116741959  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
116755346  ENDOG; endonuclease G, mitochondrial [KO:K01173]
116747854  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
116745555  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
116755387  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116761601  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116760890  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
116761675  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116757708  CAPN1; LOW QUALITY PROTEIN: calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
116740338  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
116764185  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
116748072  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
116761029  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
116760113  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
116754944  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
116758007  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
116758017  CTSD; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
116758736  CTSF; LOW QUALITY PROTEIN: cathepsin F [KO:K01373] [EC:3.4.22.41]
116749231  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
116750388  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
116755825  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
116756127  CTSL; cathepsin L1 isoform X1 [KO:K01365] [EC:3.4.22.15]
116754219  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
116738968  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
116757425  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
116740042  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
116757989  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
116758079  BIRC2; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2 [KO:K16060]
116747379  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
116747138  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 5-like [KO:K08731]
116745382  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
116764419  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
116739841  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
116738931  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
116762662  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
116762851  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
116756065  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
116763459  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
116754735  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116741257  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116751302  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116758242  BAD; bcl2-associated agonist of cell death [KO:K02158]
116761115  JUN; transcription factor AP-1 [KO:K04448]
116749519  FOS; proto-oncogene c-Fos [KO:K04379]
116745739  TP53; cellular tumor antigen p53 [KO:K04451]
116739085  HRK; activator of apoptosis harakiri [KO:K02512]
116745052  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
116741676  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116746707  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
116747398  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
116749797  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
116754222  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116758150  RELA; transcription factor p65 isoform X1 [KO:K04735]
116754069  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
116756129  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
116740948  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
116752262  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
116755406  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
116747450  BCL2A1; LOW QUALITY PROTEIN: bcl-2-related protein A1 [KO:K02162]
116757857  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
116758839  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
116744488  BBC3; bcl-2-binding component 3 [KO:K10132]
116739138  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
116759648  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
116754467  NGF; beta-nerve growth factor [KO:K02582]
116756746  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
116751037  interleukin-3-like [KO:K04736]
116746994  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
116760186  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
116752953  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116752990  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
116751286  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116750604  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116742613  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
116751944  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116739722  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
116743673  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116759669  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116748950  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116757893  HRAS; GTPase HRas isoform X1 [KO:K02833]
116751649  uncharacterized protein LOC116751649 [KO:K02833]
116760326  KRAS; GTPase KRas isoform X1 [KO:K07827]
116739088  NRAS; GTPase NRas [KO:K07828]
116761625  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116747589  MAP2K1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116751189  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116738910  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116740620  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
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
Related
pathway
psiu04010  MAPK signaling pathway
psiu04020  Calcium signaling pathway
psiu04064  NF-kappa B signaling pathway
psiu04115  p53 signaling pathway
psiu04141  Protein processing in endoplasmic reticulum
psiu04151  PI3K-Akt signaling pathway
psiu04650  Natural killer cell mediated cytotoxicity
psiu04668  TNF signaling pathway
KO pathway
ko04210   
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