KEGG   PATHWAY: rbb04210
Entry
rbb04210                    Pathway                                
Name
Apoptosis - Rhinopithecus bieti (black snub-nosed monkey)
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
rbb04210  Apoptosis
rbb04210

Other DBs
GO: 0006915
Organism
Rhinopithecus bieti (black snub-nosed monkey) [GN:rbb]
Gene
108512087  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
108512498  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108512689  [KO:K02187] [EC:3.4.22.56]
108512787  SPTAN1; spectrin alpha chain, non-erythrocytic 1 [KO:K06114]
108512788  ENDOG; LOW QUALITY PROTEIN: endonuclease G, mitochondrial [KO:K01173]
108513008  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
108513174  [KO:K04741] [EC:3.4.22.-]
108514076  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
108514077  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
108514229  RIPK1; LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
108514363  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
108514672  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108515190  GZMB; granzyme B isoform X1 [KO:K01353] [EC:3.4.21.79]
108515408  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
108515410  PARP4; poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.-]
108515415  [KO:K28177]
108515416  NOL3; nucleolar protein 3 [KO:K28177]
108515510  LMNA; lamin isoform X1 [KO:K12641]
108515538  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
108516255  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
108516259  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
108517380  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
108517508  [KO:K04440] [EC:2.7.11.24]
108517986  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
108518065  BCL2L11; LOW QUALITY PROTEIN: bcl-2-like protein 11 [KO:K16341]
108518420  [KO:K07374]
108518477  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
108518640  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
108518671  CTSF; LOW QUALITY PROTEIN: cathepsin F [KO:K01373] [EC:3.4.22.41]
108518784  IKBKG; NF-kappa-B essential modulator [KO:K07210]
108518882  EIF2AK3; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
108519636  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108519663  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.-]
108519685  DDIT3; DNA damage-inducible transcript 3 protein isoform X1 [KO:K04452]
108520255  TNF; tumor necrosis factor isoform X1 [KO:K03156]
108520463  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
108520611  PTPN13; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
108520941  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
108521141  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108521151  [KO:K01365] [EC:3.4.22.15]
108521156  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
108521631  SEPT4; septin-4 isoform X1 [KO:K16943]
108521880  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108521978  IL3; interleukin-3 [KO:K04736]
108522968  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
108523380  AIFM1; LOW QUALITY PROTEIN: apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
108523439  [KO:K08738]
108523458  [KO:K10132]
108523624  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
108523695  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
108523739  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
108523748  KRAS; GTPase KRas isoform X1 [KO:K07827]
108524009  [KO:K08738]
108524131  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
108524269  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
108524923  [KO:K08738]
108525461  [KO:K07374]
108525726  [KO:K07374]
108526259  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
108526400  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
108526412  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
108526609  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
108527305  PARP2; poly [ADP-ribose] polymerase 2 [KO:K28005]
108528122  NRAS; GTPase NRas [KO:K07828]
108528126  NGF; beta-nerve growth factor isoform X1 [KO:K02582]
108528248  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
108528737  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
108529021  CTSO; LOW QUALITY PROTEIN: cathepsin O [KO:K01374] [EC:3.4.22.42]
108529277  CTSV; cathepsin L2 [KO:K01375] [EC:3.4.22.43]
108529896  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
108530087  [KO:K08738]
108530336  PRF1; perforin-1 [KO:K07818]
108531312  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
108531449  LMNB2; lamin-B2 isoform X1 [KO:K07611]
108531451  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
108531686  HTRA2; serine protease HTRA2, mitochondrial isoform X1 [KO:K08669] [EC:3.4.21.108]
108532002  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
108532107  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
108532119  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
108532216  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
108532817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
108532870  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
108532915  [KO:K08738]
108532921  JUN; transcription factor AP-1 [KO:K04448]
108532960  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108533261  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
108533262  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
108533266  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
108533297  [KO:K08738]
108533712  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
108534125  ACTG1; actin, cytoplasmic 2 [KO:K05692]
108534183  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
108534276  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108534930  FOS; proto-oncogene c-Fos [KO:K04379]
108535077  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
108535521  [KO:K08738]
108535636  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108535931  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
108535981  DFFB; LOW QUALITY PROTEIN: DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
108536070  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108536259  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
108536287  [KO:K08738]
108536511  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
108536689  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
108537084  DAB2IP; LOW QUALITY PROTEIN: disabled homolog 2-interacting protein [KO:K19901]
108537107  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
108537706  LMNB1; lamin-B1 [KO:K07611]
108537794  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
108537955  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A [KO:K04722]
108538232  [KO:K05692]
108538237  ACTB; actin, cytoplasmic 1 [KO:K05692]
108538612  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
108538647  CTSH; pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
108538660  BCL2A1; bcl-2-related protein A1 isoform X1 [KO:K02162]
108538801  FADD; FAS-associated death domain protein [KO:K02373]
108538827  [KO:K08738]
108539069  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108539152  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
108539346  DFFA; DNA fragmentation factor subunit alpha isoform X1 [KO:K02310]
108539355  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108540273  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
108540415  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
108540719  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108540791  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B isoform X1 [KO:K04722]
108541015  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
108541060  DIABLO; diablo homolog, mitochondrial isoform X1 [KO:K10522]
108541175  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
108541622  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
108541711  BID; BH3-interacting domain death agonist [KO:K04726]
108541714  TUBA8; tubulin alpha-8 chain [KO:K07374]
108542466  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
108542734  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
108542901  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
108543285  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
108543421  [KO:K01365] [EC:3.4.22.15]
108543462  APAF1; LOW QUALITY PROTEIN: apoptotic protease-activating factor 1 [KO:K02084]
108543519  RELA; transcription factor p65 [KO:K04735]
108543525  HRAS; GTPase HRas isoform X1 [KO:K02833]
108544234  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
108544591  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
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
rbb04010  MAPK signaling pathway
rbb04020  Calcium signaling pathway
rbb04064  NF-kappa B signaling pathway
rbb04115  p53 signaling pathway
rbb04141  Protein processing in endoplasmic reticulum
rbb04151  PI3K-Akt signaling pathway
rbb04650  Natural killer cell mediated cytotoxicity
rbb04668  TNF signaling pathway
KO pathway
ko04210   

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