KEGG   PATHWAY: ko04210Help
Entry
ko04210                     Pathway                                

Name
Apoptosis
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
ko04210

All organismsOrtholog table
Module
M00685  
Apoptotic machinery [PATH:ko04210]
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
Other DBs
BSID: 
GO: 
Orthology
K04389  
tumor necrosis factor ligand superfamily member 6
K04390  
tumor necrosis factor receptor superfamily member 6
K04721  
tumor necrosis factor ligand superfamily member 10
K04722  
tumor necrosis factor receptor superfamily member 10
K03156  
tumor necrosis factor superfamily, member 2
K03158  
tumor necrosis factor receptor superfamily member 1A
K04383  
interleukin 1 alpha
K04519  
interleukin 1 beta
K04386  
interleukin 1 receptor type I
K04723  
interleukin 1 receptor accessory protein
K02373  
FAS-associated death domain protein
K03171  
tumor necrosis factor receptor type 1-associated DEATH domain protein
K04724  
CASP8 and FADD-like apoptosis regulator
K04400  
caspase 10 [EC:3.4.22.63]
K04398  
caspase 8 [EC:3.4.22.61]
K02187  
caspase 3 [EC:3.4.22.56]
K04397  
caspase 7 [EC:3.4.22.60]
K04396  
caspase 6 [EC:3.4.22.59]
K16060  
baculoviral IAP repeat-containing protein 2/3
K04725  
E3 ubiquitin-protein ligase XIAP
K16061  
baculoviral IAP repeat-containing protein 7/8
K04726  
BH3 interacting domain death agonist
K02161  
apoptosis regulator BCL-2
K04570  
BCL2-like 1 (apoptosis regulator Bcl-X)
K08738  
cytochrome c
K02084  
apoptotic protease-activating factor
K04399  
caspase 9 [EC:3.4.22.62]
K02310  
DNA fragmentation factor, 45 kD, alpha subunit
K02311  
DNA fragmentation factor, 40 kD, beta subunit [EC:3.-.-.-]
K04727  
programmed cell death 8 (apoptosis-inducing factor) [EC:1.-.-.-]
K01173  
endonuclease G, mitochondrial
K04728  
ataxia telangiectasia mutated family protein [EC:2.7.11.1]
K04451  
tumor protein p53
K02861  
receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]
K03173  
TNF receptor-associated factor 2
K04729  
myeloid differentiation primary response protein MyD88
K04730  
interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K04731  
interleukin-1 receptor-associated kinase 2 [EC:2.7.11.1]
K04732  
interleukin-1 receptor-associated kinase 3 [EC:2.7.11.1]
K04733  
interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K04466  
mitogen-activated protein kinase kinase kinase 14 [EC:2.7.11.25]
K04467  
inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  
inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  
inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734  
NF-kappa-B inhibitor alpha
K02580  
nuclear factor NF-kappa-B p105 subunit
K04735  
transcription factor p65
K02582  
nerve growth factor, beta
K03176  
neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]
K04736  
interleukin 3
K04737  
interleukin 3 receptor alpha
K04738  
cytokine receptor common subunit beta
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153]
K02649  
phosphoinositide-3-kinase, regulatory subunit
K04456  
RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04739  
cAMP-dependent protein kinase regulator
K04345  
protein kinase A [EC:2.7.11.11]
K02158  
BCL2-antagonist of cell death
K02159  
apoptosis regulator BAX
K04348  
serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  
serine/threonine-protein phosphatase 2B regulatory subunit
K01367  
calpain-1 [EC:3.4.22.52]
K03853  
calpain-2 [EC:3.4.22.53]
K04741  
caspase 12 [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)

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