KEGG   PATHWAY: mjv04210
Entry
mjv04210                    Pathway                                
Name
Apoptosis - Manis javanica (Malayan pangolin)
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
mjv04210  Apoptosis
mjv04210

Other DBs
GO: 0006915
Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108383338  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
108383372  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
108383375  [KO:K07374]
108383561  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108383873  [KO:K07374]
108384433  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
108384893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108385046  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X3 [KO:K04369] [EC:2.7.12.2]
108385222  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
108385599  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
108385635  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
108386081  NGF; beta-nerve growth factor [KO:K02582]
108386605  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
108386817  JUN; transcription factor Jun [KO:K04448]
108386996  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
108387124  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
108387612  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
108388244  [KO:K07611]
108388261  [KO:K01365] [EC:3.4.22.15]
108389002  IL3RA; interleukin-3 receptor subunit alpha isoform X4 [KO:K04737]
108389053  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
108389075  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
108389250  [KO:K07374]
108389793  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
108390232  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 isoform X2 [KO:K10131]
108390322  NOL3; nucleolar protein 3 [KO:K28177]
108390345  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
108390365  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108390389  DIABLO; diablo IAP-binding mitochondrial protein isoform X1 [KO:K10522]
108390475  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
108390484  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108391115  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
108391145  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
108391321  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
108391706  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
108392479  TUBA4B; LOW QUALITY PROTEIN: putative tubulin-like protein alpha-4B [KO:K07374]
108392608  [KO:K01353] [EC:3.4.21.79]
108392655  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
108393012  [KO:K07374]
108393091  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
108393107  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
108393208  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A [KO:K04722]
108393239  LMNB2; lamin-B2 isoform X1 [KO:K07611]
108393260  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
108393592  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
108393746  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
108393837  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
108394341  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
108394726  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
108394828  BCL2L11; bcl-2-like protein 11 isoform X7 [KO:K16341]
108394955  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
108395345  TUBA4A; tubulin alpha-4A chain isoform X1 [KO:K07374]
108395422  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
108395771  ENDOG; endonuclease G, mitochondrial isoform X1 [KO:K01173]
108395842  KRAS; GTPase KRas isoform X1 [KO:K07827]
108395952  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 [KO:K04958]
108395975  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
108396077  CYCS; cytochrome c [KO:K08738]
108396152  DAXX; death domain-associated protein 6 [KO:K02308]
108396850  TUBA8; tubulin alpha-8 chain isoform X2 [KO:K07374]
108396943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
108397005  RELA; transcription factor p65 isoform X1 [KO:K04735]
108397369  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
108397433  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108397533  CASP6; caspase-6 isoform X3 [KO:K04396] [EC:3.4.22.59]
108397877  TNF; tumor necrosis factor [KO:K03156]
108398002  PRF1; perforin-1 isoform X2 [KO:K07818]
108398047  NRAS; GTPase NRas [KO:K07828]
108398454  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108398556  [KO:K01365] [EC:3.4.22.15]
108398862  BBC3; bcl-2-binding component 3 [KO:K10132]
108399216  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
108399769  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
108399795  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108399811  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X4 [KO:K06276] [EC:2.7.11.1]
108400192  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
108400315  BAX; apoptosis regulator BAX isoform X2 [KO:K02159]
108400663  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
108400727  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
108400819  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
108400975  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
108401094  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
108401155  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
108401337  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
108401438  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
108401442  FADD; FAS-associated death domain protein [KO:K02373]
108401585  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
108402276  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
108402523  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108402534  FOS; protein c-Fos [KO:K04379]
108402938  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X2 [KO:K04960]
108402940  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
108403236  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
108403274  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
108403293  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform X1 [KO:K04959]
108403692  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
108404026  CTSS; cathepsin S isoform X2 [KO:K01368] [EC:3.4.22.27]
108404249  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070]
108404266  TP53; cellular tumor antigen p53 [KO:K04451]
108404750  CASP8; caspase-8 isoform X5 [KO:K04400] [EC:3.4.22.63]
108404831  [KO:K01365] [EC:3.4.22.15]
108404832  [KO:K01365] [EC:3.4.22.15]
108404892  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
108405074  LMNA; lamin [KO:K12641]
108405156  DAB2IP; disabled homolog 2-interacting protein isoform X10 [KO:K19901]
108406748  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
108406827  TRAF2; TNF receptor-associated factor 2 isoform X4 [KO:K03173] [EC:2.3.2.27]
108407571  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
108407801  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
108408263  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
108408627  HRAS; GTPase HRas isoform X1 [KO:K02833]
108408650  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
108408777  BCL2A1; bcl-2-related protein A1 [KO:K02162]
108409586  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
108410297  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
108410344  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
118967667  [KO:K02833]
118972008  [KO:K07611]
140842979  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
140842982  [KO:K02833]
140843067  [KO:K02833]
140845628  TUBAL3; LOW QUALITY PROTEIN: tubulin alpha chain-like 3 [KO:K07374]
140848090  [KO:K07374]
140848621  [KO:K16943]
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
mjv04010  MAPK signaling pathway
mjv04020  Calcium signaling pathway
mjv04064  NF-kappa B signaling pathway
mjv04115  p53 signaling pathway
mjv04141  Protein processing in endoplasmic reticulum
mjv04151  PI3K-Akt signaling pathway
mjv04650  Natural killer cell mediated cytotoxicity
mjv04668  TNF signaling pathway
KO pathway
ko04210   

DBGET integrated database retrieval system