KEGG   PATHWAY: ppad04210
Entry
ppad04210                   Pathway                                
Name
Apoptosis - Panthera pardus (leopard)
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
ppad04210  Apoptosis
ppad04210

Other DBs
GO: 0006915
Organism
Panthera pardus (leopard) [GN:ppad]
Gene
109245932  TP53; cellular tumor antigen p53 [KO:K04451]
109246663  BAD; bcl2-associated agonist of cell death [KO:K02158]
109246719  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
109246747  RELA; transcription factor p65 isoform X1 [KO:K04735]
109246765  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
109246807  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
109246925  [KO:K04722]
109246999  FADD; FAS-associated death domain protein [KO:K02373]
109247194  CUNH17orf47; uncharacterized protein C17orf47 homolog [KO:K16943]
109247199  SEPT4; septin-4 isoform X1 [KO:K16943]
109247385  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109247606  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109247882  PARP3; poly [ADP-ribose] polymerase 3 isoform X1 [KO:K10798] [EC:2.4.2.-]
109248009  PLA2G12A; group XIIA secretory phospholipase A2 isoform X1 [KO:K04396] [EC:3.4.22.59]
109249063  TUBA1B; tubulin alpha-1B chain [KO:K07374]
109249064  [KO:K07374]
109249287  [KO:K07374]
109249466  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
109249879  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
109250060  ENDOG; endonuclease G, mitochondrial [KO:K01173]
109250065  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
109250200  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
109250719  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
109250815  IL3; interleukin-3 [KO:K04736]
109250941  LMNB1; lamin-B1 isoform X1 [KO:K07611]
109251018  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
109251167  ACTB; actin, cytoplasmic 1 [KO:K05692]
109251379  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109251630  [KO:K01365] [EC:3.4.22.15]
109251669  [KO:K01365] [EC:3.4.22.15]
109251670  [KO:K01365] [EC:3.4.22.15]
109251671  [KO:K01365] [EC:3.4.22.15]
109251673  [KO:K01365] [EC:3.4.22.15]
109251674  [KO:K01365] [EC:3.4.22.15]
109251680  [KO:K01365] [EC:3.4.22.15]
109251681  [KO:K01365] [EC:3.4.22.15]
109252525  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
109252887  BBC3; bcl-2-binding component 3 [KO:K10132]
109253092  [KO:K02159]
109253093  [KO:K02159]
109253096  [KO:K02159]
109253320  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109253464  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
109253759  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
109253856  FOS; proto-oncogene c-Fos [KO:K04379]
109253878  [KO:K07374]
109254652  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
109254955  [KO:K01353] [EC:3.4.21.79]
109254957  [KO:K01353] [EC:3.4.21.79]
109255367  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
109255747  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
109255967  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
109256147  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
109256198  LMNA; lamin [KO:K12641]
109256209  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
109256498  [KO:K07374]
109256570  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109256986  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
109257023  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
109257065  CTSS; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
109257492  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109257521  [KO:K16060]
109257526  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
109257673  LMNB2; lamin-B2 isoform X1 [KO:K07611]
109257746  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109257810  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109258173  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
109258466  [KO:K04741] [EC:3.4.22.-]
109258604  [KO:K07374]
109258781  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
109258888  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
109259106  PARP4; poly [ADP-ribose] polymerase 4 isoform X1 [KO:K10798] [EC:2.4.2.-]
109259409  CTSD; LOW QUALITY PROTEIN: cathepsin D [KO:K01379] [EC:3.4.23.5]
109259699  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109259759  [KO:K02833]
109259786  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
109259912  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109260532  TNF; tumor necrosis factor [KO:K03156]
109260755  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
109260756  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
109260762  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
109260771  [KO:K01365] [EC:3.4.22.15]
109261148  IKBKG; NF-kappa-B essential modulator [KO:K07210]
109261343  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109261661  [KO:K07374]
109261721  [KO:K07210]
109262264  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
109262395  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
109262485  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
109262816  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109263345  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
109264370  PRF1; perforin-1 isoform X1 [KO:K07818]
109264550  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109264822  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
109265033  [KO:K07374]
109265383  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
109265519  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
109265586  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109266705  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109266785  JUN; transcription factor AP-1 [KO:K04448]
109266953  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109267324  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
109268294  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
109268745  KRAS; GTPase KRas isoform X1 [KO:K07827]
109268756  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
109269169  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
109269619  [KO:K08738]
109269863  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
109269887  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
109270377  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
109270786  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
109270789  NOL3; nucleolar protein 3 isoform X1 [KO:K28177]
109271430  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
109271451  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
109271454  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
109272105  NRAS; GTPase NRas [KO:K07828]
109272115  NGF; beta-nerve growth factor [KO:K02582]
109272592  BCL2L1; bcl-2-like protein 1 [KO:K04570]
109272766  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109272923  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
109273563  BCL2A1; bcl-2-related protein A1 [KO:K02162]
109273576  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
109273788  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
109274003  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
109274075  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109274096  DFFA; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
109274153  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
109275060  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109275136  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
109275159  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109275530  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109275625  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
109275651  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
109276143  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
109276279  BID; BH3-interacting domain death agonist [KO:K04726]
109276285  TUBA8; tubulin alpha-8 chain [KO:K07374]
109276310  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
109276314  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
109276785  ACTG1; actin, cytoplasmic 2 [KO:K05692]
109276862  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
109277087  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
109277583  HRK; activator of apoptosis harakiri [KO:K02512]
109277707  DIABLO; diablo homolog, mitochondrial [KO:K10522]
109278175  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
109278700  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
109278973  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [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
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
ppad04010  MAPK signaling pathway
ppad04020  Calcium signaling pathway
ppad04064  NF-kappa B signaling pathway
ppad04115  p53 signaling pathway
ppad04141  Protein processing in endoplasmic reticulum
ppad04151  PI3K-Akt signaling pathway
ppad04650  Natural killer cell mediated cytotoxicity
ppad04668  TNF signaling pathway
KO pathway
ko04210   

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