KEGG   PATHWAY: afz04210
Entry
afz04210                    Pathway                                
Name
Apoptosis - Antechinus flavipes (yellow-footed antechinus)
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
afz04210  Apoptosis
afz04210

Other DBs
GO: 0006915
Organism
Antechinus flavipes (yellow-footed antechinus) [GN:afz]
Gene
127552879  tumor necrosis factor ligand superfamily member 10 [KO:K04721]
127562897  tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
127552171  LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 6 [KO:K04390]
127540264  FAS-associated death domain protein [KO:K02373]
127559172  tumor necrosis factor [KO:K03156]
127538963  tumor necrosis factor receptor superfamily member 1A [KO:K03158]
127547929  tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
127553230  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
127553228  caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
127553229  caspase-10 [KO:K04400] [EC:3.4.22.63]
127541990  caspase-6-like isoform X1 [KO:K04396] [EC:3.4.22.59]
127542048  caspase-3 [KO:K02187] [EC:3.4.22.56]
127551594  caspase-7 [KO:K04397] [EC:3.4.22.60]
127538163  BH3-interacting domain death agonist isoform X1 [KO:K04726]
127556582  apoptosis regulator BAX [KO:K02159]
127561143  bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
127545428  diablo IAP-binding mitochondrial protein [KO:K10522]
127541189  serine protease HTRA2, mitochondrial [KO:K08669] [EC:3.4.21.108]
127564362  cytochrome c, somatic [KO:K08738]
127538855  cytochrome c-like [KO:K08738]
127554527  cytochrome c 2-like [KO:K08738]
127564838  apoptotic protease-activating factor 1 [KO:K02084]
127555841  caspase-9 [KO:K04399] [EC:3.4.22.62]
127552079  perforin-1 [KO:K07818]
127549370  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
127549371  granzyme-like protein 1 [KO:K01353] [EC:3.4.21.79]
127564084  tubulin alpha-1C chain [KO:K07374]
127564152  tubulin alpha-8 chain [KO:K07374]
127562711  tubulin alpha-8 chain [KO:K07374]
127538419  tubulin alpha-8 chain-like [KO:K07374]
127538906  tubulin alpha-1A chain [KO:K07374]
127538907  tubulin alpha-1B chain isoform X1 [KO:K07374]
127545775  tubulin alpha-3 chain [KO:K07374]
127545800  tubulin alpha-3 chain [KO:K07374]
127553080  tubulin alpha-1D chain isoform X1 [KO:K07374]
127553081  tubulin alpha-4A chain [KO:K07374]
127559106  induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
127563434  actin, cytoplasmic 1 isoform X1 [KO:K05692]
127542395  actin, cytoplasmic 1-like [KO:K05692]
127551984  actin, cytoplasmic type 5 [KO:K05692]
127560651  actin, cytoplasmic 2 [KO:K05692]
127547611  actin, cytoskeletal 4-like [KO:K05692]
127550857  spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114]
127559791  lamin [KO:K12641]
127545138  lamin-B2 [KO:K07611]
127560193  lamin-B1 isoform X1 [KO:K07611]
127559548  poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
127549147  poly [ADP-ribose] polymerase 2 isoform X1 [KO:K10798] [EC:2.4.2.30]
127554154  protein mono-ADP-ribosyltransferase PARP3 [KO:K10798] [EC:2.4.2.30]
127554770  protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798] [EC:2.4.2.30]
127555888  DNA fragmentation factor subunit alpha [KO:K02310]
127555951  DNA fragmentation factor subunit beta isoform X1 [KO:K02311] [EC:3.-.-.-]
127550867  endonuclease G, mitochondrial [KO:K01173]
127542416  apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
127560415  serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
127549124  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
127551451  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
127539174  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
127561144  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
127541787  calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
127559523  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
127554934  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
127547478  eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
127549650  eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
127538329  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
127538074  DNA damage-inducible transcript 3 protein [KO:K04452]
127543788  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
127548524  cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
127555164  dipeptidyl peptidase 1 [KO:K01275] [EC:3.4.14.1]
127541930  cathepsin D [KO:K01379] [EC:3.4.23.5]
127540320  cathepsin F [KO:K01373] [EC:3.4.22.41]
127551417  pro-cathepsin H isoform X1 [KO:K01366] [EC:3.4.22.16]
127559104  cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
127546809  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
127561750  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
127561737  procathepsin L-like [KO:K01365] [EC:3.4.22.15]
127539995  cathepsin O [KO:K01374] [EC:3.4.22.42]
127559107  cathepsin S [KO:K01368] [EC:3.4.22.27]
127541795  cathepsin W isoform X1 [KO:K08569] [EC:3.4.22.-]
127548966  cathepsin Z [KO:K08568] [EC:3.4.18.1]
127554917  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
127554918  baculoviral IAP repeat-containing protein 3-like isoform X1 [KO:K16060]
127543223  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
127560698  baculoviral IAP repeat-containing protein 5 [KO:K08731]
127548399  bcl-2-like protein 11 isoform X1 [KO:K16341]
127550456  bcl-2-like protein 1 isoform X1 [KO:K04570]
127543678  apoptosis regulator Bcl-2 [KO:K02161]
127561120  death domain-associated protein 6 [KO:K02308]
127544228  receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
127550541  disabled homolog 2-interacting protein isoform X1 [KO:K19901]
127562250  mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
127542137  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
127550306  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
127551815  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
127540994  bcl2-associated agonist of cell death [KO:K02158]
127563247  transcription factor Jun [KO:K04448]
127549484  protein c-Fos [KO:K04379]
127560870  cellular tumor antigen p53 isoform X1 [KO:K04451]
127545519  activator of apoptosis harakiri [KO:K02512]
127560369  mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
127548272  inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
127542289  NF-kappa-B essential modulator isoform X1 [KO:K07210]
127549751  NF-kappa-B inhibitor alpha [KO:K04734]
127541094  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
127540746  transcription factor p65 isoform X1 [KO:K04735]
127541095  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 13 [KO:K02374]
127563174  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
127545137  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
127552133  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
127550532  TNF receptor-associated factor 1 [KO:K03172]
127547132  bcl-2-related protein A1 [KO:K02162]
127554958  serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
127541737  p53-induced death domain-containing protein 1 [KO:K10130]
127556256  bcl-2-binding component 3 isoform X1 [KO:K10132]
127538416  LOW QUALITY PROTEIN: caspase-2 [KO:K02186] [EC:3.4.22.55]
127559262  beta-nerve growth factor [KO:K02582]
127559757  high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
127553686  interleukin-3 receptor subunit alpha-like isoform X1 [KO:K04737]
127553694  interleukin-3 receptor subunit alpha-like [KO:K04737]
127538147  cytokine receptor common subunit beta isoform X1 [KO:K04738]
127555896  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
127552891  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
127554245  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
127563398  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
127558297  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
127545225  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
127563028  LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1-like [KO:K06276] [EC:2.7.11.1]
127542756  3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
127549861  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127556193  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127559596  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127540068  GTPase HRas [KO:K02833]
127564364  ras-like protein [KO:K07827]
127564665  ras-like protein [KO:K07827]
127564806  GTPase KRas isoform X1 [KO:K07827]
127564858  GTPase KRas-like [KO:K07827]
127564890  ras-like protein [KO:K07827]
127564892  GTPase NRas-like [KO:K07827]
127541495  ras-like protein [KO:K07827]
127537819  GTPase NRas-like [KO:K07827]
127537860  GTPase NRas-like [KO:K07827]
127538037  ras-like protein [KO:K07827]
127538119  ras-like protein [KO:K07827]
127538128  LOW QUALITY PROTEIN: ras-like protein [KO:K07827]
127538787  ras-like protein [KO:K07827]
127538953  ras-like protein [KO:K07827]
127539191  ras-like protein [KO:K07827]
127539349  GTPase NRas-like [KO:K07827]
127539435  ras-like protein [KO:K07827]
127539441  ras protein let-60-like [KO:K07827]
127541494  ras-like protein [KO:K07828]
127559280  GTPase NRas [KO:K07828]
127538788  GTPase NRas-like [KO:K07828]
127538790  GTPase NRas-like [KO:K07828]
127538791  GTPase NRas-like [KO:K07828]
127538792  GTPase NRas-like [KO:K07828]
127538794  GTPase NRas-like [KO:K07828]
127552087  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
127551242  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
127544950  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
127556083  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
127545795  mitogen-activated protein kinase 1 isoform X1 [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
afz04010  MAPK signaling pathway
afz04020  Calcium signaling pathway
afz04064  NF-kappa B signaling pathway
afz04115  p53 signaling pathway
afz04141  Protein processing in endoplasmic reticulum
afz04151  PI3K-Akt signaling pathway
afz04650  Natural killer cell mediated cytotoxicity
afz04668  TNF signaling pathway
KO pathway
ko04210   
LinkDB

DBGET integrated database retrieval system