KEGG   PATHWAY: pdic04210
Entry
pdic04210                   Pathway                                
Name
Apoptosis - Phyllostomus discolor (pale spear-nosed bat)
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
pdic04210  Apoptosis
pdic04210

Other DBs
GO: 0006915
Organism
Phyllostomus discolor (pale spear-nosed bat) [GN:pdic]
Gene
114490557  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
114503748  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
114512032  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
114497076  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
114489990  FADD; FAS-associated death domain protein [KO:K02373]
114495334  TNF; tumor necrosis factor isoform X1 [KO:K03156]
114514124  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
114488446  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
114494605  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
114494575  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
114494329  CASP10; caspase-10 isoform X2 [KO:K04400] [EC:3.4.22.63]
114492304  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
114508735  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
114497398  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
114508724  BID; BH3-interacting domain death agonist [KO:K04726]
114510992  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
114494928  BAK1; LOW QUALITY PROTEIN: bcl-2 homologous antagonist/killer [KO:K14021]
114509784  DIABLO; diablo homolog, mitochondrial [KO:K10522]
114503096  septin-4 isoform X1 [KO:K16943]
114500921  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
114499664  cytochrome c-like [KO:K08738]
114506519  cytochrome c-like [KO:K08738]
114508100  cytochrome c [KO:K08738]
114506811  cytochrome c-like [KO:K08738]
114512815  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
114497767  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
114497807  PRF1; perforin-1 [KO:K07818]
114492846  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
114492848  granzyme B(G,H)-like isoform X1 [KO:K01353] [EC:3.4.21.79]
114492886  cathepsin G-like [KO:K01353] [EC:3.4.21.79]
114492957  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
114495658  tubulin alpha-4A chain [KO:K07374]
114509275  tubulin alpha-3 chain [KO:K07374]
114510140  LOW QUALITY PROTEIN: tubulin alpha-3 chain [KO:K07374]
114512626  LOW QUALITY PROTEIN: tubulin alpha chain-like [KO:K07374]
114492318  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
114513013  tubulin alpha-1A chain [KO:K07374]
114513014  tubulin alpha-1B chain isoform X1 [KO:K07374]
114513015  TUBA1C; tubulin alpha-1C chain isoform X2 [KO:K07374]
114494211  tubulin alpha-1D chain-like isoform X1 [KO:K07374]
114508573  TUBA8; tubulin alpha-8 chain isoform X1 [KO:K07374]
114488771  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
114504029  ACTG1; actin, cytoplasmic 2 [KO:K05692]
114509151  ACTB; actin, cytoplasmic 1 [KO:K05692]
114496672  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X3 [KO:K06114]
114488783  LMNA; lamin [KO:K12641]
114502778  LMNB2; lamin-B2 [KO:K07611]
114501516  LMNB1; lamin-B1 isoform X1 [KO:K07611]
114512309  PARP1; poly [ADP-ribose] polymerase 1 isoform X2 [KO:K24070] [EC:2.4.2.30]
114490297  PARP2; poly [ADP-ribose] polymerase 2 isoform X4 [KO:K10798] [EC:2.4.2.30]
114512806  PARP4; LOW QUALITY PROTEIN: protein mono-ADP-ribosyltransferase PARP4 [KO:K10798] [EC:2.4.2.30]
114501772  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X2 [KO:K10798] [EC:2.4.2.30]
114497696  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
114497518  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
114506401  ENDOG; endonuclease G, mitochondrial [KO:K01173]
114504640  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
114503814  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
114504307  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
114501461  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
114513086  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
114493819  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
114499495  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
114512462  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
114499895  LOW QUALITY PROTEIN: inactive caspase-12-like [KO:K04741] [EC:3.4.22.-]
114496093  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
114492274  EIF2S1; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
114500522  LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2 subunit 1-like [KO:K03237]
114512782  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114512688  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
114503270  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
114499527  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
114499337  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
114499790  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
114488579  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
114489030  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
114512568  cathepsin L1-like isoform X1 [KO:K01365] [EC:3.4.22.15]
114512577  CTSV; cathepsin L2 [KO:K01365] [EC:3.4.22.15]
114503348  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
114489220  CTSS; cathepsin S isoform X2 [KO:K01368] [EC:3.4.22.27]
114500471  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
114506467  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
114498544  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
114500581  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
114504538  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
114503458  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
114490782  baculoviral IAP repeat-containing protein 5-like [KO:K08731]
114500015  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
114506927  BCL2L1; bcl-2-like protein 1 [KO:K04570]
114507071  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
114493976  DAXX; death domain-associated protein 6 [KO:K02308]
114497608  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
114493992  disabled homolog 2-interacting protein isoform X1 [KO:K19901]
114494013  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X2 [KO:K04426] [EC:2.7.11.25]
114509631  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
114496029  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
114492422  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
114499526  BAD; bcl2-associated agonist of cell death isoform X2 [KO:K02158]
114496428  JUN; transcription factor AP-1 [KO:K04448]
114493153  FOS; proto-oncogene c-Fos [KO:K04379]
114515376  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
114510136  HRK; activator of apoptosis harakiri [KO:K02512]
114502860  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
114496345  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
114508493  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
114504586  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
114492937  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
114492465  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
114499888  RELA; transcription factor p65 [KO:K04735]
114491494  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X3 [KO:K02374]
114497596  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
114504094  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
114512579  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
114507728  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
114488659  BCL2A1; bcl-2-related protein A1 [KO:K02162]
114498399  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
114499330  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
114511715  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
114507019  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
114507769  CASP2; caspase-2 isoform X4 [KO:K02186] [EC:3.4.22.55]
114488932  NGF; beta-nerve growth factor [KO:K02582]
114489015  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
114510347  IL3; interleukin-3 [KO:K04736]
114489875  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
114513933  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
114497407  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114490993  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114501452  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114496100  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114502559  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
114501063  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114495251  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
114510957  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114512350  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114492688  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114499504  HRAS; GTPase HRas isoform X2 [KO:K02833]
114512682  KRAS; GTPase KRas isoform X1 [KO:K07827]
114489186  NRAS; GTPase NRas [KO:K07828]
114501905  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
114491735  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
114503388  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114510156  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114496946  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
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
pdic04010  MAPK signaling pathway
pdic04020  Calcium signaling pathway
pdic04064  NF-kappa B signaling pathway
pdic04115  p53 signaling pathway
pdic04141  Protein processing in endoplasmic reticulum
pdic04151  PI3K-Akt signaling pathway
pdic04650  Natural killer cell mediated cytotoxicity
pdic04668  TNF signaling pathway
KO pathway
ko04210   
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