KEGG   PATHWAY: aml04210
Entry
aml04210                    Pathway                                
Name
Apoptosis - Ailuropoda melanoleuca (giant panda)
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
aml04210  Apoptosis
aml04210

Other DBs
GO: 0006915
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100463573  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
105235183  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
100468235  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
100473767  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
100468003  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
100471563  TNF; tumor necrosis factor [KO:K03156]
100479926  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100483589  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
100474872  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X4 [KO:K04724]
100472842  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
100475128  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
100476854  caspase-6 isoform X2 [KO:K04396] [EC:3.4.22.59]
117795025  caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
100469056  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
100471992  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
100465439  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
100471095  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100472241  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
100468220  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
100470052  SEPTIN4; septin-4 isoform X1 [KO:K16943]
100471770  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
100472074  cytochrome c [KO:K08738]
105241648  cytochrome c-like [KO:K08738]
100464163  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
100483760  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
100473675  PRF1; perforin-1 [KO:K07818]
100464420  granzyme B [KO:K01353] [EC:3.4.21.79]
100480515  tubulin alpha-8 chain [KO:K07374]
100468269  TUBA4B; LOW QUALITY PROTEIN: putative tubulin-like protein alpha-4B [KO:K07374]
100470688  LOW QUALITY PROTEIN: tubulin alpha-3 chain [KO:K07374]
100463766  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
100464995  TUBAL3; tubulin alpha chain-like 3 isoform X1 [KO:K07374]
100475162  LOW QUALITY PROTEIN: tubulin alpha-1C chain [KO:K07374]
100466505  tubulin alpha-4A chain isoform X2 [KO:K07374]
100484433  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
100466132  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100481739  actin [KO:K05692]
117800125  actin, cytoplasmic 1 [KO:K05692]
117800181  actin, cytoplasmic type 5 isoform X1 [KO:K05692]
117800361  actin, cytoplasmic 1-like [KO:K05692]
117800408  actin, cytoplasmic 1 [KO:K05692]
100483165  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
100469629  LMNA; lamin [KO:K12641]
100475957  LMNB1; lamin-B1 [KO:K07611]
100466430  LMNB2; lamin-B2 [KO:K07611]
100478353  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
100483143  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
100479913  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.30]
100483457  PARP4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.30]
100480275  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
100479584  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
100472161  ENDOG; endonuclease G, mitochondrial [KO:K01173]
100471854  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
100474476  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
100474087  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100467161  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
100477888  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100471747  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100468407  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
100476150  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100465168  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
100479743  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
100470706  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
100476284  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100479063  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
100476830  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
100464355  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
100464994  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
100483888  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
100481013  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
100483004  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
100484313  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
100476216  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
105238104  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
100476469  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
100482864  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
100483259  CTSS; cathepsin S isoform X1 [KO:K01368] [EC:3.4.22.27]
100479650  CTSW; cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
100473166  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
100477152  baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100477406  baculoviral IAP repeat-containing protein 2 [KO:K16060]
100471203  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100475314  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
100477763  BCL2L11; bcl-2-like protein 11 isoform X2 [KO:K16341]
100469922  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100484344  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
100484332  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
100469872  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
100463723  DAB2IP; LOW QUALITY PROTEIN: disabled homolog 2-interacting protein [KO:K19901]
100475304  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
100477951  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100482196  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100477600  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
100473937  BAD; bcl2-associated agonist of cell death [KO:K02158]
100483834  JUN; transcription factor AP-1 [KO:K04448]
100474867  FOS; proto-oncogene c-Fos [KO:K04379]
100468516  TP53; cellular tumor antigen p53 [KO:K04451]
100472260  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
100464675  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100471679  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100470223  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100466997  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100467906  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100480158  RELA; transcription factor p65 isoform X1 [KO:K04735]
100477379  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X11 [KO:K02374]
100477654  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
100482871  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100470600  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100464979  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
100468997  BCL2A1; bcl-2-related protein A1 [KO:K02162]
100480638  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
100463959  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
100474559  bcl-2-binding component 3, isoforms 1/2 [KO:K10132]
100474991  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
100474060  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
100469695  NGF; beta-nerve growth factor [KO:K02582]
100473242  interleukin-3 [KO:K04736]
105238362  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
100477536  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100473305  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100473836  HRAS; GTPase HRas isoform X1 [KO:K02833]
100483919  KRAS; GTPase KRas isoform X1 [KO:K07827]
100464196  NRAS; GTPase NRas [KO:K07828]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C00319  Sphingosine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Savitskaya MA, Onishchenko GE
  Title
Mechanisms of Apoptosis.
  Journal
Biochemistry (Mosc) 80:1393-417 (2015)
DOI:10.1134/S0006297915110012
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Safa AR
  Title
c-FLIP, a master anti-apoptotic regulator.
  Journal
Exp Oncol 34:176-84 (2012)
Reference
  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
  Authors
Parsons MJ, Green DR
  Title
Mitochondria in cell death.
  Journal
Essays Biochem 47:99-114 (2010)
DOI:10.1042/bse0470099
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Logue SE, Martin SJ
  Title
Caspase activation cascades in apoptosis.
  Journal
Biochem Soc Trans 36:1-9 (2008)
DOI:10.1042/BST0360001
Reference
  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
  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
aml04010  MAPK signaling pathway
aml04020  Calcium signaling pathway
aml04064  NF-kappa B signaling pathway
aml04115  p53 signaling pathway
aml04141  Protein processing in endoplasmic reticulum
aml04151  PI3K-Akt signaling pathway
aml04650  Natural killer cell mediated cytotoxicity
aml04668  TNF signaling pathway
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system