KEGG   PATHWAY: biu04210
Entry
biu04210                    Pathway                                

Name
Apoptosis - Bos indicus (zebu cattle)
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
biu04210  Apoptosis
biu04210

Other DBs
GO: 0006915
Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109558018  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
109563119  tumor necrosis factor receptor superfamily member 10B-like isoform X1 [KO:K04722]
109570480  tumor necrosis factor ligand superfamily member 6 [KO:K04389]
109570785  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
109579171  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
109554562  FADD; FAS-associated death domain protein [KO:K02373]
109577428  TNF; tumor necrosis factor [KO:K03156]
109559729  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
109572519  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
109569493  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
109569521  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
109560257  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
109553316  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
109553157  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
109559782  BH3-interacting domain death agonist-like isoform X1 [KO:K04726]
109559783  BH3-interacting domain death agonist-like isoform X1 [KO:K04726]
109571977  apoptosis regulator BAX [KO:K02159]
109571778  BAX; apoptosis regulator BAX [KO:K02159]
109577301  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
109571379  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
109574217  SEPT4; septin-4 isoform X1 [KO:K16943]
109565903  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
109566483  cytochrome c [KO:K08738]
109566484  cytochrome c [KO:K08738]
109557512  cytochrome c [KO:K08738]
109559418  APAF1; LOW QUALITY PROTEIN: apoptotic protease-activating factor 1 [KO:K02084]
109570433  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
109553933  PRF1; perforin-1 [KO:K07818]
109575715  duodenase-1 isoform X1 [KO:K01353] [EC:3.4.21.79]
109575716  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
109575719  duodenase-1-like [KO:K01353] [EC:3.4.21.79]
109575720  duodenase-1-like [KO:K01353] [EC:3.4.21.79]
109575204  LOW QUALITY PROTEIN: mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
109575773  duodenase-1 [KO:K01353] [EC:3.4.21.79]
109575279  granzyme B-like [KO:K01353] [EC:3.4.21.79]
109571179  tubulin alpha-3 chain [KO:K07374]
109559138  tubulin alpha-1A chain isoform X1 [KO:K07374]
109559139  tubulin alpha-1C chain [KO:K07374]
109559140  tubulin alpha-1C chain-like [KO:K07374]
109559142  tubulin alpha-1B chain [KO:K07374]
109563249  tubulin alpha-1A chain-like [KO:K07374]
109559787  TUBA8; tubulin alpha-8 chain [KO:K07374]
109568071  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
109570981  tubulin alpha-3 chain-like [KO:K07374]
109572490  tubulin alpha-1C chain-like [KO:K07374]
109571050  TUBA4A; tubulin alpha-4A chain [KO:K07374]
109571090  tubulin alpha-1D chain [KO:K07374]
109555382  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
109564155  induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
109573916  ACTG1; actin, cytoplasmic 2 [KO:K05692]
109566517  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
109578943  SPTA1; spectrin alpha chain, erythrocytic 1 [KO:K06114]
109553357  LMNA; lamin [KO:K12641]
109561789  LMNB2; lamin-B2 [KO:K07611]
109561846  LMNB1; lamin-B1 [KO:K07611]
109570525  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070] [EC:2.4.2.30]
109564883  PARP2; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 2 [KO:K10798] [EC:2.4.2.30]
109575871  PARP3; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
109567055  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
109570543  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
109570366  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
109566525  ENDOG; endonuclease G, mitochondrial [KO:K01173]
109555268  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
109574052  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
109566626  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
109576135  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
109558547  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
109576552  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
109554508  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
109570370  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
109566145  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
109565265  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 isoform X1 [KO:K03237]
109559832  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109559326  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
109562776  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
109554360  CTSC; dipeptidyl peptidase 1 isoform X1 [KO:K01275] [EC:3.4.14.1]
109554428  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
109554136  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
109575407  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
109555331  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
109563231  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
109571466  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
109555340  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
109554432  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
109567290  CTSZ; cathepsin Z isoform X1 [KO:K08568] [EC:3.4.18.1]
109555878  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
109568764  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
109569840  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
109574440  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
109565710  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
109567345  BCL2L1; bcl-2-like protein 1 [KO:K04570]
109565507  bcl-2-like protein 1 [KO:K04570]
109577782  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
109576585  DAXX; death domain-associated protein 6 [KO:K02308]
109577264  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
109566418  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
109563980  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
109561331  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
109560650  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
109553773  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109554386  BAD; bcl2-associated agonist of cell death [KO:K02158]
109556235  JUN; transcription factor AP-1 [KO:K04448]
109565363  FOS; proto-oncogene c-Fos [KO:K04379]
109574238  TP53; cellular tumor antigen p53 [KO:K04451]
109574056  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
109553086  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109553353  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
109575581  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109560296  NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
109554392  RELA; transcription factor p65 [KO:K04735]
109560653  PTPN13; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
109561788  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109556176  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109563283  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109563408  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
109575747  BCL2A1; bcl-2-related protein A1 [KO:K02162]
109569718  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
109571765  BBC3; bcl-2-binding component 3 [KO:K10132]
109577992  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
109557747  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
109555882  NGF; beta-nerve growth factor [KO:K02582]
109556725  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
109561219  interleukin-3 [KO:K04736]
109559524  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109578066  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
109572496  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109570286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109560940  GTPase HRas-like [KO:K02833]
109559581  KRAS; GTPase KRas isoform X1 [KO:K07827]
109555890  NRAS; GTPase NRas [KO:K07828]
109576053  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
109564697  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109561751  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109578667  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109570973  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
  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
biu04010  MAPK signaling pathway
biu04020  Calcium signaling pathway
biu04064  NF-kappa B signaling pathway
biu04115  p53 signaling pathway
biu04141  Protein processing in endoplasmic reticulum
biu04151  PI3K-Akt signaling pathway
biu04650  Natural killer cell mediated cytotoxicity
biu04668  TNF signaling pathway
KO pathway
ko04210   

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