KEGG   PATHWAY: padl04210
Entry
padl04210                   Pathway                                
Name
Apoptosis - Pygoscelis adeliae (Adelie penguin)
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
padl04210  Apoptosis
padl04210

Other DBs
GO: 0006915
Organism
Pygoscelis adeliae (Adelie penguin) [GN:padl]
Gene
103924981  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
103914004  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
103913942  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
103925771  FADD; FAS-associated death domain protein [KO:K02373]
103922177  tumor necrosis factor receptor superfamily member 1A-like [KO:K03158]
103914203  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
103923407  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
103924262  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
103923440  caspase-8-like [KO:K04398] [EC:3.4.22.61]
103923449  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
103919543  CASP6; caspase-6 [KO:K04396] [EC:3.4.22.59]
103922530  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
103918570  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
103926227  caspase-3-like [KO:K04397] [EC:3.4.22.60]
103924359  BID; BH3-interacting domain death agonist [KO:K04726]
103919822  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
103914569  DIABLO; diablo homolog, mitochondrial [KO:K10522]
103912889  septin-4-like [KO:K16943]
103922175  HTRA2; serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
103918416  cytochrome c [KO:K08738]
103923966  LOW QUALITY PROTEIN: cytochrome c, somatic-like [KO:K08738]
103914625  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
103918063  CASP9; LOW QUALITY PROTEIN: caspase-9 [KO:K04399] [EC:3.4.22.62]
103913812  tubulin alpha-8 chain [KO:K07374]
103920502  TUBA4A; tubulin alpha-4A chain [KO:K07374]
103917691  tubulin alpha chain [KO:K07374]
103925283  tubulin alpha-3 chain [KO:K07374]
103924356  TUBA8; tubulin alpha-8 chain [KO:K07374]
103924357  tubulin alpha-4 chain-like [KO:K07374]
103920837  tubulin alpha-3 chain [KO:K07374]
103922812  TUBAL3; tubulin alpha chain-like 3 isoform X1 [KO:K07374]
103913345  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
103913542  ACTB; actin, cytoplasmic 1 [KO:K05692]
103915307  SPTAN1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
103913899  lamin-A-like [KO:K12641]
103913203  LMNB1; lamin-B1 [KO:K07611]
103916054  LMNB2; lamin-B2 isoform X1 [KO:K07611]
103922724  lamin-L(III)-like [KO:K07611]
103925012  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
103915050  PARP3; poly [ADP-ribose] polymerase 3 [KO:K10798] [EC:2.4.2.30]
103926395  PARP4; LOW QUALITY PROTEIN: poly [ADP-ribose] polymerase 4 [KO:K10798] [EC:2.4.2.30]
103918038  DFFA; DNA fragmentation factor subunit alpha [KO:K02310]
103913967  DFFB; DNA fragmentation factor subunit beta [KO:K02311] [EC:3.-.-.-]
103915382  ENDOG; endonuclease G, mitochondrial [KO:K01173]
103925908  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
103913928  ERN2; LOW QUALITY PROTEIN: serine/threonine-protein kinase/endoribonuclease IRE2 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
103916657  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
103921138  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
103922482  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103924320  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103919873  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103922858  CAPN11; LOW QUALITY PROTEIN: calpain-11 [KO:K01367] [EC:3.4.22.52]
103925056  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
103923526  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
103914348  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
103915003  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103913274  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
103914925  CTSC; dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
103920685  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
103914793  CTSH; pro-cathepsin H [KO:K01366] [EC:3.4.22.16]
103920403  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
103921821  CTSO; cathepsin O [KO:K01374] [EC:3.4.22.42]
103919476  cathepsin S-like [KO:K01368] [EC:3.4.22.27]
103919480  cathepsin S-like [KO:K01368] [EC:3.4.22.27]
103919374  CTSZ; cathepsin Z [KO:K08568] [EC:3.4.18.1]
103918923  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
103922595  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
103922195  BCL2L1; bcl-2-like protein 1 [KO:K04570]
103919231  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
103919013  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
103915321  DAB2IP; disabled homolog 2-interacting protein [KO:K19901]
103912745  MAP3K5; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
103915758  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103913739  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103918603  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103913320  JUN; transcription factor AP-1 [KO:K04448]
103921921  MAP3K14; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
103924297  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103920554  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103912947  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103919520  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
103918684  PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
103921611  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103915325  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
103922712  BCL2A1; bcl-2-related protein A1 [KO:K02162]
103926402  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
103916447  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
103912216  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
103920778  CASP2; caspase-2 [KO:K02186] [EC:3.4.22.55]
103923574  NGF; beta-nerve growth factor [KO:K02582]
103924143  LOW QUALITY PROTEIN: cytokine receptor common subunit beta-like [KO:K04738]
103924175  LOW QUALITY PROTEIN: cytokine receptor common subunit beta-like [KO:K04738]
103914966  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103917840  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103917969  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103926435  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103919717  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103919124  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103913922  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
103914586  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103919989  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103916212  LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
103916453  HRAS; GTPase HRas [KO:K02833]
103924322  KRAS; GTPase KRas isoform X1 [KO:K07827]
103923578  NRAS; GTPase NRas [KO:K07828]
103915210  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103914812  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103916484  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103922585  MAPK1; LOW QUALITY PROTEIN: 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
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
padl04010  MAPK signaling pathway
padl04020  Calcium signaling pathway
padl04115  p53 signaling pathway
padl04141  Protein processing in endoplasmic reticulum
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system