KEGG   PATHWAY: mmu04210Help
Entry
mmu04210                    Pathway                                

Name
Apoptosis - Mus musculus (mouse)
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
BRITE hierarchy
Pathway map
Apoptosis
mmu04210

All organismsOrtholog table
Module
Apoptotic machinery [PATH:mmu04210]
Other DBs
BSID: 
GO: 
Organism
Mus musculus (mouse) [GN:mmu]
Gene
22035  
Tnfsf10; tumor necrosis factor (ligand) superfamily, member 10 [KO:K04721]
21933  
Tnfrsf10b; tumor necrosis factor receptor superfamily, member 10b [KO:K04722]
14103  
Fasl; Fas ligand (TNF superfamily, member 6) [KO:K04389]
14102  
Fas; Fas (TNF receptor superfamily member 6) [KO:K04390]
14082  
Fadd; Fas (TNFRSF6)-associated via death domain [KO:K02373]
21926  
Tnf; tumor necrosis factor [KO:K03156]
21937  
Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158]
71609  
Tradd; TNFRSF1A-associated via death domain [KO:K03171]
tumor necrosis factor receptor type 1-associated DEATH domain protein; K03171 tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
12633  
Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
12370  
Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
12368  
Casp6; caspase 6 [KO:K04396] [EC:3.4.22.59]
12367  
Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
12369  
Casp7; caspase 7 [KO:K04397] [EC:3.4.22.60]
12122  
Bid; BH3 interacting domain death agonist [KO:K04726]
12028  
Bax; BCL2-associated X protein [KO:K02159]
12018  
Bak1; BCL2-antagonist/killer 1 [KO:K14021]
66593  
Diablo; diablo, IAP-binding mitochondrial protein [KO:K10522]
18952  
Sept4; septin 4 [KO:K16943]
64704  
Htra2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
13063  
Cycs; cytochrome c, somatic [KO:K08738]
13067  
Cyct; cytochrome c, testis [KO:K08738]
11783  
Apaf1; apoptotic peptidase activating factor 1 [KO:K02084]
12371  
Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
18646  
Prf1; perforin 1 (pore forming protein) [KO:K07818]
14939  
Gzmb; granzyme B [KO:K01353] [EC:3.4.21.79]
22145  
Tuba4a; tubulin, alpha 4A [KO:K07374]
22144  
Tuba3a; tubulin, alpha 3A [KO:K07374]
22142  
Tuba1a; tubulin, alpha 1A [KO:K07374]
22146  
Tuba1c; tubulin, alpha 1C [KO:K07374]
22147  
Tuba3b; tubulin, alpha 3B [KO:K07374]
22143  
Tuba1b; tubulin, alpha 1B [KO:K07374]
53857  
Tuba8; tubulin, alpha 8 [KO:K07374]
238463  
Tubal3; tubulin, alpha-like 3 [KO:K07374]
17210  
Mcl1; myeloid cell leukemia sequence 1 [KO:K02539]
11461  
Actb; actin, beta [KO:K05692]
11465  
Actg1; actin, gamma, cytoplasmic 1 [KO:K05692]
20739  
Spta1; spectrin alpha, erythrocytic 1 [KO:K06114]
20740  
Sptan1; spectrin alpha, non-erythrocytic 1 [KO:K06114]
16905  
Lmna; lamin A [KO:K12641]
16906  
Lmnb1; lamin B1 [KO:K07611]
16907  
Lmnb2; lamin B2 [KO:K07611]
11546  
Parp2; poly (ADP-ribose) polymerase family, member 2 [KO:K10798] [EC:2.4.2.30]
11545  
Parp1; poly (ADP-ribose) polymerase family, member 1 [KO:K10798] [EC:2.4.2.30]
235587  
Parp3; poly (ADP-ribose) polymerase family, member 3 [KO:K10798] [EC:2.4.2.30]
328417  
Parp4; poly (ADP-ribose) polymerase family, member 4 [KO:K10798] [EC:2.4.2.30]
13347  
Dffa; DNA fragmentation factor, alpha subunit [KO:K02310]
13368  
Dffb; DNA fragmentation factor, beta subunit [KO:K02311] [EC:3.-.-.-]
13804  
Endog; endonuclease G [KO:K01173]
26926  
Aifm1; apoptosis-inducing factor, mitochondrion-associated 1 [KO:K04727] [EC:1.-.-.-]
78943  
Ern1; endoplasmic reticulum (ER) to nucleus signalling 1 [KO:K08852] [EC:3.1.26.- 2.7.11.1]
22030  
Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
16438  
Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  
Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  
Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
12333  
Capn1; calpain 1 [KO:K01367] [EC:3.4.22.52]
12334  
Capn2; calpain 2 [KO:K03853] [EC:3.4.22.53]
12364  
Casp12; caspase 12 [KO:K04741] [EC:3.4.22.-]
13666  
Eif2ak3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
13665  
Eif2s1; eukaryotic translation initiation factor 2, subunit 1 alpha [KO:K03237]
11911  
Atf4; activating transcription factor 4 [KO:K04374]
13198  
Ddit3; DNA-damage inducible transcript 3 [KO:K04452]
13030  
Ctsb; cathepsin B [KO:K01363] [EC:3.4.22.1]
13032  
Ctsc; cathepsin C [KO:K01275] [EC:3.4.14.1]
13033  
Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
56464  
Ctsf; cathepsin F [KO:K01373] [EC:3.4.22.41]
13036  
Ctsh; cathepsin H [KO:K01366] [EC:3.4.22.16]
13038  
Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
13039  
Ctsl; cathepsin L [KO:K01365] [EC:3.4.22.15]
229445  
Ctso; cathepsin O [KO:K01374] [EC:3.4.22.42]
13040  
Ctss; cathepsin S [KO:K01368] [EC:3.4.22.27]
13041  
Ctsw; cathepsin W [KO:K08569] [EC:3.4.22.-]
64138  
Ctsz; cathepsin Z [KO:K08568] [EC:3.4.18.1]
11797  
Birc2; baculoviral IAP repeat-containing 2 [KO:K16060]
11796  
Birc3; baculoviral IAP repeat-containing 3 [KO:K16060]
11798  
Xiap; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
11799  
Birc5; baculoviral IAP repeat-containing 5 [KO:K08731]
12125  
Bcl2l11; BCL2-like 11 (apoptosis facilitator) [KO:K16341]
12048  
Bcl2l1; BCL2-like 1 [KO:K04570]
12043  
Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]
13163  
Daxx; Fas death domain-associated protein [KO:K02308]
19766  
Ripk1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
69601  
Dab2ip; disabled 2 interacting protein [KO:K19901]
26408  
Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
26419  
Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  
Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  
Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
12015  
Bad; BCL2-associated agonist of cell death [KO:K02158]
16476  
Jun; jun proto-oncogene [KO:K04448]
14281  
Fos; FBJ osteosarcoma oncogene [KO:K04379]
22059  
Trp53; transformation related protein 53 [KO:K04451]
12123  
Hrk; harakiri, BCL2 interacting protein (contains only BH3 domain) [KO:K02512]
53859  
Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
12675  
Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  
Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
16151  
Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
18035  
Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  
Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  
Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
19249  
Ptpn13; protein tyrosine phosphatase, non-receptor type 13 [KO:K02374]
13197  
Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402]
17873  
Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402]
23882  
Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402]
22029  
Traf1; TNF receptor-associated factor 1 [KO:K03172]
12047  
Bcl2a1d; B cell leukemia/lymphoma 2 related protein A1d [KO:K02162]
12044  
Bcl2a1a; B cell leukemia/lymphoma 2 related protein A1a [KO:K02162]
12045  
Bcl2a1b; B cell leukemia/lymphoma 2 related protein A1b [KO:K02162]
12046  
Bcl2a1c; B cell leukemia/lymphoma 2 related protein A1c [KO:K02162]
11920  
Atm; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
57913  
Pidd1; p53 induced death domain protein 1 [KO:K10130]
170770  
Bbc3; BCL2 binding component 3 [KO:K10132]
58801  
Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
12366  
Casp2; caspase 2 [KO:K02186] [EC:3.4.22.55]
18049  
Ngf; nerve growth factor [KO:K02582]
18211  
Ntrk1; neurotrophic tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
16187  
Il3; interleukin 3 [KO:K04736]
16188  
Il3ra; interleukin 3 receptor, alpha chain [KO:K04737]
12984  
Csf2rb2; colony stimulating factor 2 receptor, beta 2, low-affinity (granulocyte-macrophage) [KO:K04738]
12983  
Csf2rb; colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) [KO:K04738]
30955  
Pik3cg; phosphoinositide-3-kinase, catalytic, gamma polypeptide [KO:K00922] [EC:2.7.1.153]
18706  
Pik3ca; phosphatidylinositol 3-kinase, catalytic, alpha polypeptide [KO:K00922] [EC:2.7.1.153]
18707  
Pik3cd; phosphatidylinositol 3-kinase catalytic delta polypeptide [KO:K00922] [EC:2.7.1.153]
74769  
Pik3cb; phosphatidylinositol 3-kinase, catalytic, beta polypeptide [KO:K00922] [EC:2.7.1.153]
18709  
Pik3r2; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 (p85 beta) [KO:K02649]
18708  
Pik3r1; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) [KO:K02649]
320207  
Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5, p101 [KO:K02649]
18710  
Pik3r3; phosphatidylinositol 3 kinase, regulatory subunit, polypeptide 3 (p55) [KO:K02649]
18607  
Pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
11651  
Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  
Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  
Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
15461  
Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  
Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  
Nras; neuroblastoma ras oncogene [KO:K07828]
110157  
Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  
Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  
Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  
Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  
Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
Compound
C00027  
Hydrogen peroxide
C00076  
Calcium cation
C00319  
Sphingosine
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Savitskaya MA, Onishchenko GE
  Title
Mechanisms of Apoptosis.
  Journal
Biochemistry (Mosc) 80:1393-417 (2015)
Reference
  Authors
Schleich K, Lavrik IN
  Title
Mathematical modeling of apoptosis.
  Journal
Cell Commun Signal 11:44 (2013)
Reference
  Authors
Lavrik I, Golks A, Krammer PH
  Title
Death receptor signaling.
  Journal
J Cell Sci 118:265-7 (2005)
Reference
  Authors
Jin Z, El-Deiry WS
  Title
Overview of cell death signaling pathways.
  Journal
Cancer Biol Ther 4:139-63 (2005)
Reference
  Authors
Benn SC, Woolf CJ
  Title
Adult neuron survival strategies--slamming on the brakes.
  Journal
Nat Rev Neurosci 5:686-700 (2004)
Reference
  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)
Reference
  Authors
Clarke P, Tyler KL
  Title
Apoptosis in animal models of virus-induced disease.
  Journal
Nat Rev Microbiol 7:144-55 (2009)
Reference
  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)
Reference
  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)
Reference
  Authors
Philchenkov A
  Title
Caspases: potential targets for regulating cell death.
  Journal
J Cell Mol Med 8:432-44 (2004)
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)
Reference
  Authors
Safa AR
  Title
c-FLIP, a master anti-apoptotic regulator.
  Journal
Exp Oncol 34:176-84 (2012)
Reference
  Authors
Jeong SY, Seol DW
  Title
The role of mitochondria in apoptosis.
  Journal
BMB Rep 41:11-22 (2008)
Reference
  Authors
Parsons MJ, Green DR
  Title
Mitochondria in cell death.
  Journal
Essays Biochem 47:99-114 (2010)
Reference
  Authors
Strasser A
  Title
The role of BH3-only proteins in the immune system.
  Journal
Nat Rev Immunol 5:189-200 (2005)
Reference
  Authors
Schonthal AH
  Title
Endoplasmic reticulum stress: its role in disease and novel prospects for therapy.
  Journal
Scientifica (Cairo) 2012:857516 (2012)
Reference
  Authors
Malhi H, Kaufman RJ
  Title
Endoplasmic reticulum stress in liver disease.
  Journal
J Hepatol 54:795-809 (2011)
Reference
  Authors
Malhotra JD, Kaufman RJ
  Title
The endoplasmic reticulum and the unfolded protein response.
  Journal
Semin Cell Dev Biol 18:716-31 (2007)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Dashzeveg N, Yoshida K
  Title
Cell death decision by p53 via control of the mitochondrial membrane.
  Journal
Cancer Lett 367:108-12 (2015)
Reference
  Authors
Bouchier-Hayes L, Green DR
  Title
Caspase-2: the orphan caspase.
  Journal
Cell Death Differ 19:51-7 (2012)
Reference
  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)
Reference
  Authors
Aggarwal BB
  Title
Signalling pathways of the TNF superfamily: a double-edged sword.
  Journal
Nat Rev Immunol 3:745-56 (2003)
Reference
  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)
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)
Reference
  Authors
Sofroniew MV, Howe CL, Mobley WC
  Title
Nerve growth factor signaling, neuroprotection, and neural repair.
  Journal
Annu Rev Neurosci 24:1217-81 (2001)
Reference
  Authors
Kristiansen M, Ham J
  Title
Programmed cell death during neuronal development: the sympathetic neuron model.
  Journal
Cell Death Differ 21:1025-35 (2014)
Reference
  Authors
Logue SE, Martin SJ
  Title
Caspase activation cascades in apoptosis.
  Journal
Biochem Soc Trans 36:1-9 (2008)
Reference
  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)
Reference
  Authors
Cullen SP, Brunet M, Martin SJ
  Title
Granzymes in cancer and immunity.
  Journal
Cell Death Differ 17:616-23 (2010)
KO pathway
 

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