KEGG   PATHWAY: mbez04210
Entry
mbez04210                   Pathway                                
Name
Apoptosis - Moschus berezovskii (Chinese forest musk deer)
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
mbez04210  Apoptosis
mbez04210

Other DBs
GO: 0006915
Organism
Moschus berezovskii (Chinese forest musk deer) [GN:mbez]
Gene
129535684  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
129535887  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
129536224  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
129536239  [KO:K08738]
129536409  TUBA8; tubulin alpha-8 chain [KO:K07374]
129536648  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
129536687  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129536741  [KO:K07374]
129536760  [KO:K07374]
129536761  [KO:K07374]
129536762  [KO:K07374]
129537143  [KO:K02310]
129537164  KRAS; GTPase KRas isoform X1 [KO:K07827]
129537221  DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452]
129537261  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
129537598  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
129537982  [KO:K07374]
129538041  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
129538092  [KO:K07374]
129538389  [KO:K08738]
129538419  [KO:K04570]
129538551  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
129538979  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
129539173  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
129539188  [KO:K16943]
129539222  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
129539258  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
129539421  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
129539739  ENDOG; endonuclease G, mitochondrial [KO:K01173]
129539970  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
129540299  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
129540547  [KO:K04374]
129540610  JUN; transcription factor Jun [KO:K04448]
129540725  LMNA; lamin [KO:K12641]
129540753  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
129540801  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129540962  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
129541318  NGF; beta-nerve growth factor isoform X1 [KO:K02582]
129541406  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
129541549  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
129541604  [KO:K01374] [EC:3.4.22.42]
129541808  NRAS; GTPase NRas [KO:K07828]
129542259  DIABLO; diablo IAP-binding mitochondrial protein [KO:K10522]
129542485  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129542669  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
129543141  TP53; cellular tumor antigen p53 [KO:K04451]
129543262  TNF; tumor necrosis factor isoform X1 [KO:K03156]
129543626  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
129543652  DAXX; death domain-associated protein 6 [KO:K02308]
129543713  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
129543844  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
129544511  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
129544549  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
129544620  ACTG1; actin, cytoplasmic 2 [KO:K05692]
129544663  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
129545284  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
129545501  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129545548  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
129545772  ACTB; actin, cytoplasmic 1 [KO:K05692]
129546572  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
129546622  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
129546814  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129547022  NOL3; nucleolar protein 3 isoform X1 [KO:K28177]
129547027  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
129547146  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129547721  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129547888  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
129548039  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
129548597  HRAS; GTPase HRas isoform X1 [KO:K02833]
129548608  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
129548627  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
129548659  FADD; FAS-associated death domain protein [KO:K02373]
129548723  CTSF; cathepsin F isoform X1 [KO:K01373] [EC:3.4.22.41]
129548748  [KO:K08569] [EC:3.4.22.-]
129548753  [KO:K08569] [EC:3.4.22.-]
129548767  RELA; transcription factor p65 [KO:K04735]
129548783  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
129548816  BAD; bcl2-associated agonist of cell death [KO:K02158]
129549076  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
129549305  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
129549430  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
129549902  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129550080  [KO:K01353] [EC:3.4.21.79]
129550130  [KO:K01353] [EC:3.4.21.79]
129550131  [KO:K01353] [EC:3.4.21.79]
129550345  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
129550351  BCL2A1; bcl-2-related protein A1 [KO:K02162]
129550478  [KO:K01353] [EC:3.4.21.79]
129550480  [KO:K01353] [EC:3.4.21.79]
129550521  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129550706  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129551094  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
129551377  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
129551459  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
129551508  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129551521  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
129551602  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129551629  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
129551654  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
129552526  [KO:K08738]
129552733  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
129553207  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
129554248  [KO:K16060]
129554250  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
129554297  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
129554739  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
129555080  PRF1; perforin-1 [KO:K07818]
129555337  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
129555451  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
129555563  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
129555633  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
129556409  PARP4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
129556896  [KO:K04722]
129556985  [KO:K01365] [EC:3.4.22.15]
129556994  [KO:K01365] [EC:3.4.22.15]
129557215  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
129557483  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
129558359  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
129558523  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129558732  [KO:K04736]
129559060  LMNB2; lamin-B2 [KO:K07611]
129559156  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129559467  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
129559478  LMNB1; lamin-B1 [KO:K07611]
129560696  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
129561494  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
129561624  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
129561625  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
129562040  BCL2L1; bcl-2-like protein 1 [KO:K04570]
129562101  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
129562372  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
129562548  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
129562722  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 isoform X1 [KO:K03237]
129563123  FOS; protein c-Fos [KO:K04379]
129564146  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
129564296  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
129564389  [KO:K16060]
129564539  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
129564549  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
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
mbez04010  MAPK signaling pathway
mbez04020  Calcium signaling pathway
mbez04064  NF-kappa B signaling pathway
mbez04115  p53 signaling pathway
mbez04141  Protein processing in endoplasmic reticulum
mbez04151  PI3K-Akt signaling pathway
mbez04650  Natural killer cell mediated cytotoxicity
mbez04668  TNF signaling pathway
KO pathway
ko04210   

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