KEGG   PATHWAY: hcg04210
Entry
hcg04210                    Pathway                                
Name
Apoptosis - Hemicordylus capensis (graceful crag lizard)
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
hcg04210  Apoptosis
hcg04210

Other DBs
GO: 0006915
Organism
Hemicordylus capensis (graceful crag lizard) [GN:hcg]
Gene
128321963  NGF; beta-nerve growth factor isoform X1 [KO:K02582]
128323350  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
128323552  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
128323821  [KO:K08568] [EC:3.4.18.1]
128323870  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
128323970  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
128324175  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
128324344  BCL2L1; bcl-2-like protein 1 [KO:K04570]
128324386  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
128324461  NRAS; GTPase NRas [KO:K07828]
128324617  JUN; transcription factor Jun [KO:K04448]
128324835  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
128325022  [KO:K07374]
128325425  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
128325639  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
128325732  KRAS; GTPase KRas isoform X1 [KO:K07827]
128325832  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
128326075  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
128326288  [KO:K07374]
128326332  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
128326333  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
128326349  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
128326359  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
128326507  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
128326605  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
128327371  CTSO; cathepsin O isoform X1 [KO:K01374] [EC:3.4.22.42]
128327531  CASP6; caspase-6 isoform X1 [KO:K04396] [EC:3.4.22.59]
128327542  PTPN13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374]
128327580  [KO:K07374]
128328158  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
128328423  TUBAL3; tubulin alpha chain-like 3 [KO:K07374]
128328865  PARP2; poly [ADP-ribose] polymerase 2 isoform X1 [KO:K28005]
128328866  [KO:K07818]
128329384  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
128329391  [KO:K02159]
128329805  [KO:K02162]
128329864  [KO:K07818]
128329865  [KO:K07818]
128330005  [KO:K08738]
128330371  [KO:K07827]
128330757  [KO:K00922] [EC:2.7.1.153]
128330948  [KO:K01379] [EC:3.4.23.5]
128331404  [KO:K04451]
128331417  [KO:K04451]
128331435  [KO:K02159]
128331496  [KO:K07818]
128331536  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
128332006  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
128332565  CAPN12; calpain-12 isoform X1 [KO:K03853] [EC:3.4.22.53]
128332580  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
128333259  [KO:K08738]
128333513  [KO:K04722]
128333575  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
128333822  [KO:K04397] [EC:3.4.22.60]
128334239  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
128334753  [KO:K05692]
128334754  [KO:K05692]
128334762  [KO:K07611]
128334788  [KO:K08738]
128334828  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
128334904  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
128334943  [KO:K05692]
128335037  [KO:K05692]
128335041  [KO:K05692]
128335052  [KO:K05692]
128335063  [KO:K05692]
128335127  BCL2A1; bcl-2-related protein A1 [KO:K02162]
128335348  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
128335667  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
128336040  [KO:K16943]
128336558  ERN2; serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
128336671  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
128336777  ACTB; actin, cytoplasmic 1 [KO:K05692]
128336905  [KO:K01368] [EC:3.4.22.27]
128336952  [KO:K01368] [EC:3.4.22.27]
128337066  BAD; bcl2-associated agonist of cell death [KO:K02158]
128337178  RELA; transcription factor p65 isoform X1 [KO:K04735]
128337383  CTSW; cathepsin W [KO:K08569] [EC:3.4.22.-]
128337445  LMNA; lamin [KO:K12641]
128337469  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
128337507  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
128337580  CTSF; cathepsin F [KO:K01373] [EC:3.4.22.41]
128337698  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
128337719  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
128337905  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
128337913  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
128337955  DIABLO; diablo IAP-binding mitochondrial protein isoform X1 [KO:K10522]
128337970  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128338397  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
128338448  DFFB; DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
128338453  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
128338505  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128338746  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
128338791  ENDOG; endonuclease G, mitochondrial [KO:K01173]
128338826  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
128338845  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
128339109  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
128339275  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
128340069  [KO:K01363] [EC:3.4.22.1]
128340461  HRAS; GTPase HRas isoform X1 [KO:K02833]
128340467  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
128340731  [KO:K04722]
128340943  FOS; protein c-Fos [KO:K04379]
128340986  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
128341008  [KO:K02162]
128341723  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
128341897  [KO:K03173] [EC:2.3.2.27]
128341908  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
128341991  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
128342805  ACTG1; actin, cytoplasmic 2 [KO:K05692]
128343150  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 isoform X1 [KO:K03237]
128343333  LMNB1; lamin-B1 isoform X1 [KO:K07611]
128343472  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
128344367  [KO:K07374]
128344420  [KO:K07374]
128344520  TUBA1B; tubulin alpha-1B chain isoform X1 [KO:K07374]
128344613  DDIT3; DNA damage-inducible transcript 3 protein isoform X1 [KO:K04452]
128344722  TUBA1A; tubulin alpha-1A chain [KO:K07374]
128344776  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
128344980  PARP3; protein mono-ADP-ribosyltransferase PARP3 isoform X1 [KO:K10798] [EC:2.4.2.-]
128345171  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
128345197  [KO:K01365] [EC:3.4.22.15]
128345244  DAXX; death domain-associated protein 6 isoform X1 [KO:K02308]
128345248  LMNB2; lamin-B2 [KO:K07611]
128345274  [KO:K07374]
128345404  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
128345427  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
128345541  [KO:K01365] [EC:3.4.22.15]
128345543  [KO:K01365] [EC:3.4.22.15]
128346024  [KO:K03156]
128346030  [KO:K03158]
128346136  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
128346522  CTSL; procathepsin L [KO:K01365] [EC:3.4.22.15]
128346633  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
128346700  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128346770  CASP2; caspase-2 isoform X1 [KO:K02186] [EC:3.4.22.55]
128346907  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
128347003  [KO:K01365] [EC:3.4.22.15]
128347113  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
128347210  [KO:K01365] [EC:3.4.22.15]
128347312  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
128347397  [KO:K01365] [EC:3.4.22.15]
128347964  [KO:K01365] [EC:3.4.22.15]
128347980  [KO:K01365] [EC:3.4.22.15]
128348734  CAPN11; calpain-11 isoform X1 [KO:K01367] [EC:3.4.22.52]
128349435  [KO:K07374]
128349526  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128349908  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
128350078  PARP4; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.-]
128350175  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
128350261  [KO:K03853] [EC:3.4.22.53]
128350445  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
128350811  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128350831  [KO:K07374]
128350941  FADD; FAS-associated death domain protein [KO:K02373]
128351224  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
128351259  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
128351429  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
128351621  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128352210  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
128352295  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
128352903  [KO:K08568] [EC:3.4.18.1]
128352953  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
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
hcg04010  MAPK signaling pathway
hcg04020  Calcium signaling pathway
hcg04115  p53 signaling pathway
hcg04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   

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