KEGG   PATHWAY: sund04210
Entry
sund04210                   Pathway                                
Name
Apoptosis - Sceloporus undulatus (fence lizard)
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
sund04210  Apoptosis
sund04210

Other DBs
GO: 0006915
Organism
Sceloporus undulatus (fence lizard) [GN:sund]
Gene
121925445  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
121935055  tumor necrosis factor receptor superfamily member 10B-like isoform X1 [KO:K04722]
121927998  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
121926093  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
121922683  tumor necrosis factor-like [KO:K03156]
121922772  tumor necrosis factor-like [KO:K03156]
121922349  tumor necrosis factor receptor superfamily member 1A-like [KO:K03158]
121934733  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
121934703  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
121931437  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
121930895  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
121934729  caspase-3-like [KO:K04397] [EC:3.4.22.60]
121925218  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
121932277  BID; BH3-interacting domain death agonist [KO:K04726]
121934264  apoptosis regulator BAX-like isoform X1 [KO:K02159]
121934534  apoptosis regulator BAX-like [KO:K02159]
121929548  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
121916729  DIABLO; diablo homolog, mitochondrial [KO:K10522]
121916909  SEPTIN4; septin-4 isoform X1 [KO:K16943]
121931747  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
121918998  cytochrome c [KO:K08738]
121935403  cytochrome c [KO:K08738]
121931976  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
121936186  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
121933317  perforin-1-like [KO:K07818]
121935633  perforin-1-like isoform X1 [KO:K07818]
121927316  tubulin alpha-3 chain isoform X1 [KO:K07374]
121927819  tubulin alpha-4A chain [KO:K07374]
121928225  tubulin alpha-8 chain isoform X1 [KO:K07374]
121918283  tubulin alpha-1D chain-like [KO:K07374]
121930483  tubulin alpha-8 chain [KO:K07374]
121931532  tubulin alpha-4 chain-like [KO:K07374]
121931788  tubulin alpha-3 chain [KO:K07374]
121931792  tubulin alpha-3 chain-like [KO:K07374]
121922225  tubulin alpha-1C chain [KO:K07374]
121922314  TUBA1A; tubulin alpha-1A chain [KO:K07374]
121922335  tubulin alpha-1B chain [KO:K07374]
121915732  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
121937536  ACTB; actin, cytoplasmic 1 [KO:K05692]
121933087  actin, cytoplasmic type 5 [KO:K05692]
121934890  actin, clone 302-like [KO:K05692]
121935651  actin, cytoplasmic type 5-like [KO:K05692]
121935652  actin, clone 302-like [KO:K05692]
121921336  ACTG1; actin, cytoplasmic 2 [KO:K05692]
121937196  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
121915219  LMNA; lamin [KO:K12641]
121923370  LMNB1; lamin-B1 [KO:K07611]
121934036  lamin-L(III)-like [KO:K07611]
121937173  LMNB2; lamin-B2 isoform X1 [KO:K07611]
121915803  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
121923401  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.30]
121935026  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
121936379  DFFA; LOW QUALITY PROTEIN: DNA fragmentation factor subunit alpha [KO:K02310]
121936861  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
121936604  ENDOG; endonuclease G, mitochondrial [KO:K01173]
121936296  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
121922368  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
121914353  ERN2; LOW QUALITY PROTEIN: serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
121936587  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
121921093  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
121932190  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
121928090  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
121934501  CAPN11; LOW QUALITY PROTEIN: calpain-11 [KO:K01367] [EC:3.4.22.52]
121915106  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
121919237  CAPN2; calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
121934276  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
121928239  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
121918233  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
121931934  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
121921330  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
121931257  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
121925165  CTSC; LOW QUALITY PROTEIN: dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
121934257  cathepsin D-like [KO:K01379] [EC:3.4.23.5]
121936820  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
121915910  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
121933119  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
121916255  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
121922902  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
121935981  procathepsin L-like isoform X1 [KO:K01365] [EC:3.4.22.15]
121936543  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
121931527  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
121916254  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
121917809  LOW QUALITY PROTEIN: cathepsin W-like [KO:K08569] [EC:3.4.22.-]
121915537  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
121928250  cathepsin Z-like [KO:K08568] [EC:3.4.18.1]
121928643  cathepsin Z-like [KO:K08568] [EC:3.4.18.1]
121928644  cathepsin Z-like [KO:K08568] [EC:3.4.18.1]
121928645  cathepsin Z-like [KO:K08568] [EC:3.4.18.1]
121928915  cathepsin Z-like [KO:K08568] [EC:3.4.18.1]
121930087  cathepsin Z-like isoform X1 [KO:K08568] [EC:3.4.18.1]
121927176  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
121936807  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
121922797  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
121919573  baculoviral IAP repeat-containing protein 5.1-like [KO:K08731]
121922327  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
121929893  BCL2L1; bcl-2-like protein 1 [KO:K04570]
121929439  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
121921230  DAXX; death domain-associated protein 6 [KO:K02308]
121929823  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
121936844  disabled homolog 2-interacting protein isoform X1 [KO:K19901]
121932476  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
121923830  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
121931541  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
121928905  JUN; transcription factor AP-1 [KO:K04448]
121918920  FOS; proto-oncogene c-Fos [KO:K04379]
121932555  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
121935260  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
121925441  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
121933447  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
121922695  IKBKG; NF-kappa-B essential modulator [KO:K07210]
121919325  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
121931415  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
121915610  RELA; transcription factor p65 isoform X1 [KO:K04735]
121931115  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
121924073  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
121929554  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
121937212  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
121936031  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
121935158  BCL2A1; bcl-2-related protein A1 isoform X1 [KO:K02162]
121926777  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
121926345  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
121923468  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
121920580  CASP2; LOW QUALITY PROTEIN: caspase-2 [KO:K02186] [EC:3.4.22.55]
121928752  NGF; beta-nerve growth factor isoform X1 [KO:K02582]
121916146  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
121930315  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
121932579  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
121925257  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121925596  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121937300  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
121928626  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
121923252  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121914625  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
121934110  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121919908  AKT3; LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121915323  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121926328  HRAS; GTPase HRas [KO:K02833]
121935008  GTPase HRas [KO:K07827]
121931822  KRAS; GTPase KRas isoform X1 [KO:K07827]
121929449  NRAS; GTPase NRas [KO:K07828]
121921146  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121934449  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
121921221  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
121936502  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
121932739  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121916521  MAPK1; mitogen-activated protein kinase 1 [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
sund04010  MAPK signaling pathway
sund04020  Calcium signaling pathway
sund04115  p53 signaling pathway
sund04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system