KEGG   PATHWAY: hsa04210Help
Entry
hsa04210                    Pathway                                

Name
Apoptosis - Homo sapiens (human)
Description
Apoptosis is a genetically controlled mechanisms of cell death involved in the regulation of tissue homeostasis. The 2 major pathways of apoptosis are the extrinsic (Fas and other TNFR superfamily members and ligands) and the intrinsic (mitochondria-associated) pathways, both of which are found in the cytoplasm. The extrinsic pathway is triggered by death receptor engagement, which initiates a signaling cascade mediated by caspase-8 activation. Caspase-8 both feeds directly into caspase-3 activation and stimulates the release of cytochrome c by the mitochondria. Caspase-3 activation leads to the degradation of cellular proteins necessary to maintain cell survival and integrity. The intrinsic pathway occurs when various apoptotic stimuli trigger the release of cytochrome c from the mitochondria (independently of caspase-8 activation). Cytochrome c interacts with Apaf-1 and caspase-9 to promote the activation of caspase-3. Recent studies point to the ER as a third subcellular compartment implicated in apoptotic execution. Alterations in Ca2+ homeostasis and accumulation of misfolded proteins in the ER cause ER stress. Prolonged ER stress can result in the activation of BAD and/or caspase-12, and execute apoptosis.
Class
Cellular Processes; Cell growth and death
BRITE hierarchy
Pathway map
Apoptosis
hsa04210

All organismsOrtholog table
Disease
H00108  
Autoimmune lymphoproliferative syndromes (ALPS)
H00265  
Hereditary sensory and autonomic neuropathy (HSAN)
H00539  
PTEN hamartoma tumor syndrome (PHTS)
H00540  
Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00645  
Incontinentia pigmenti
H00721  
Pyogenic bacterial infections, recurrent, due to MYD88 deficiency
H00848  
Ataxia with ocular apraxia (AOA)
H00881  
Li-Fraumeni syndrome
H00882  
Cocoon syndrome
H00912  
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
H01007  
Choroid plexus papilloma
H01102  
Pituitary adenomas
Drug
D00742  
Etanercept (genetical recombination) (JAN)
D02597  
Adalimumab (genetical recombination) (JAN)
D02598  
Infliximab (genetical recombination) (JAN)
D02934  
Anakinra (USAN/INN)
D03441  
Certolizumab pegol (genetical recombination) (JAN)
D03645  
Daniplestim (USAN/INN)
D04695  
Leridistim (USAN/INN)
D04858  
Mapatumumab (USAN/INN)
D05090  
Muplestim (genetical recombination) (JAN)
D05146  
Nerelimomab (USAN/INN)
D05216  
Oblimersen sodium (USAN)
D06611  
Lexatumumab (USAN/INN)
D06635  
Rilonacept (USAN/INN)
D07436  
Afelimomab (INN)
D08290  
Oblimersen (INN)
D08954  
Obatoclax mesylate (USAN)
D09329  
Conatumumab (USAN/INN)
D09387  
Tanezumab (USAN/INN)
D09888  
Drozitumab (USAN/INN)
D09907  
Fulranumab (USAN/INN)
D10381  
Afuresertib (USAN)
D10382  
Afuresertib hydrochloride (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
356  
FASLG; Fas ligand (TNF superfamily, member 6) [KO:K04389]
355  
FAS; Fas cell surface death receptor [KO:K04390]
8743  
TNFSF10; tumor necrosis factor (ligand) superfamily, member 10 [KO:K04721]
8797  
TNFRSF10A; tumor necrosis factor receptor superfamily, member 10a [KO:K04722]
8795  
TNFRSF10B; tumor necrosis factor receptor superfamily, member 10b [KO:K04722]
8794  
TNFRSF10C; tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain [KO:K04722]
8793  
TNFRSF10D; tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain [KO:K04722]
7124  
TNF; tumor necrosis factor [KO:K03156]
7132  
TNFRSF1A; tumor necrosis factor receptor superfamily, member 1A [KO:K03158]
3552  
IL1A; interleukin 1, alpha [KO:K04383]
3553  
IL1B; interleukin 1, beta [KO:K04519]
3554  
IL1R1; interleukin 1 receptor, type I [KO:K04386]
3556  
IL1RAP; interleukin 1 receptor accessory protein [KO:K04723]
8772  
FADD; Fas (TNFRSF6)-associated via death domain [KO:K02373]
8717  
TRADD; TNFRSF1A-associated via death domain [KO:K03171]
8837  
CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
843  
CASP10; caspase 10, apoptosis-related cysteine peptidase [KO:K04400] [EC:3.4.22.63]
841  
CASP8; caspase 8, apoptosis-related cysteine peptidase [KO:K04398] [EC:3.4.22.61]
836  
CASP3; caspase 3, apoptosis-related cysteine peptidase [KO:K02187] [EC:3.4.22.56]
840  
CASP7; caspase 7, apoptosis-related cysteine peptidase [KO:K04397] [EC:3.4.22.60]
839  
CASP6; caspase 6, apoptosis-related cysteine peptidase [KO:K04396] [EC:3.4.22.59]
329  
BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
330  
BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
331  
XIAP; X-linked inhibitor of apoptosis [KO:K04725]
79444  
BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]
112401  
BIRC8; baculoviral IAP repeat containing 8 [KO:K16061]
637  
BID; BH3 interacting domain death agonist [KO:K04726]
596  
BCL2; B-cell CLL/lymphoma 2 [KO:K02161]
598  
BCL2L1; BCL2-like 1 [KO:K04570]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
317  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  
CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
1676  
DFFA; DNA fragmentation factor, 45kDa, alpha polypeptide [KO:K02310]
1677  
DFFB; DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase) [KO:K02311] [EC:3.-.-.-]
9131  
AIFM1; apoptosis-inducing factor, mitochondrion-associated, 1 [KO:K04727] [EC:1.-.-.-]
2021  
ENDOG; endonuclease G [KO:K01173]
472  
ATM; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
7157  
TP53; tumor protein p53 [KO:K04451]
8737  
RIPK1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
7186  
TRAF2; TNF receptor-associated factor 2 [KO:K03173]
4615  
MYD88; myeloid differentiation primary response 88 [KO:K04729]
3654  
IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
3656  
IRAK2; interleukin-1 receptor-associated kinase 2 [KO:K04731] [EC:2.7.11.1]
11213  
IRAK3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
51135  
IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
9020  
MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4792  
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
4803  
NGF; nerve growth factor (beta polypeptide) [KO:K02582]
4914  
NTRK1; neurotrophic tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
3562  
IL3; interleukin 3 [KO:K04736]
3563  
IL3RA; interleukin 3 receptor, alpha (low affinity) [KO:K04737]
1439  
CSF2RB; colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) [KO:K04738]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
5573  
PRKAR1A; protein kinase, cAMP-dependent, regulatory, type I, alpha [KO:K04739]
5576  
PRKAR2A; protein kinase, cAMP-dependent, regulatory, type II, alpha [KO:K04739]
5577  
PRKAR2B; protein kinase, cAMP-dependent, regulatory, type II, beta [KO:K04739]
5575  
PRKAR1B; protein kinase, cAMP-dependent, regulatory, type I, beta [KO:K04739]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
572  
BAD; BCL2-associated agonist of cell death [KO:K02158]
581  
BAX; BCL2-associated X protein [KO:K02159]
5530  
PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
823  
CAPN1; calpain 1, (mu/I) large subunit [KO:K01367] [EC:3.4.22.52]
824  
CAPN2; calpain 2, (m/II) large subunit [KO:K03853] [EC:3.4.22.53]
CASP12; caspase 12 (gene/pseudogene) [KO:K04741] [EC:3.4.22.-]
Reference
(Japanese)
  Authors
Murakawa M, Yonehara S.
  Title
[Apoptosis induced by death receptors.] (In Japanese)
  Journal
Experimental Medicine 19(13):1690-1694 (2001)
Reference
  Authors
Kucharczak J, Simmons MJ, Fan Y, Gelinas C.
  Title
To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.
  Journal
Oncogene 22:8961-82 (2003)
Reference
  Authors
Donovan M, Cotter TG.
  Title
Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death.
  Journal
Biochim Biophys Acta 1644:133-47 (2004)
Reference
  Authors
Sprick MR, Walczak H.
  Title
The interplay between the Bcl-2 family and death receptor-mediated apoptosis.
  Journal
Biochim Biophys Acta 1644:125-32 (2004)
Reference
  Authors
Nagata S.
  Title
Fas ligand-induced apoptosis.
  Journal
Annu Rev Genet 33:29-55 (1999)
Reference
(Japanese)
  Authors
Suda T.
  Title
[The apoptosis is Kin to the inflammation.] (In Japanese)
  Journal
Experimental Medicine 19(13):1790-1797 (2001)
Reference
  Authors
Yuan J, Yankner BA.
  Title
Apoptosis in the nervous system.
  Journal
Nature 407:802-9 (2000)
Reference
  Authors
Yuan J, Lipinski M, Degterev A.
  Title
Diversity in the mechanisms of neuronal cell death.
  Journal
Neuron 40:401-13 (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
  Authors
Martinon F, Holler N, Richard C, Tschopp J.
  Title
Activation of a pro-apoptotic amplification loop through inhibition of NF-kappaB-dependent survival signals by caspase-mediated inactivation of RIP.
  Journal
FEBS Lett 468:134-6 (2000)
Reference
  Authors
Goyal L.
  Title
Cell death inhibition: keeping caspases in check.
  Journal
Cell 104:805-8 (2001)
Reference
  Authors
Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC.
  Title
Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD.
  Journal
Science 284:339-43 (1999)
Reference
  Authors
Remillard CV, Yuan JX.
  Title
Activation of K+ channels: an essential pathway in programmed cell death.
  Journal
Am J Physiol Lung Cell Mol Physiol 286:L49-67 (2004)
Reference
PMID:9670005
  Authors
Gross A, Jockel J, Wei MC, Korsmeyer SJ.
  Title
Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis.
  Journal
EMBO J 17:3878-85 (1998)
KO pathway
 

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