Apoptosis - Homo sapiens (human)

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.

Cellular Processes; Cell growth and death

Homo sapiens (human) [GN:hsa]

(Japanese)

Murakawa M, Yonehara S.

[Apoptosis induced by death receptors.] (In Japanese)

Experimental Medicine 19(13):1690-1694 (2001)

PMID:14663476

Kucharczak J, Simmons MJ, Fan Y, Gelinas C.

To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.

Oncogene 22:8961-82 (2003)

PMID:14996498

Donovan M, Cotter TG.

Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death.

Biochim Biophys Acta 1644:133-47 (2004)

PMID:14996497

Sprick MR, Walczak H.

The interplay between the Bcl-2 family and death receptor-mediated apoptosis.

Biochim Biophys Acta 1644:125-32 (2004)

PMID:10690403

Nagata S.

Fas ligand-induced apoptosis.

Annu Rev Genet 33:29-55 (1999)

(Japanese)

Suda T.

[The apoptosis is Kin to the inflammation.] (In Japanese)

Experimental Medicine 19(13):1790-1797 (2001)

PMID:11048732

Yuan J, Yankner BA.

Apoptosis in the nervous system.

Nature 407:802-9 (2000)

PMID:14556717

Yuan J, Lipinski M, Degterev A.

Diversity in the mechanisms of neuronal cell death.

Neuron 40:401-13 (2003)

PMID:14737178

Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA.

JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis.

Leukemia 18:189-218 (2004)

PMID:10692573

Martinon F, Holler N, Richard C, Tschopp J.

Activation of a pro-apoptotic amplification loop through inhibition of NF-kappaB-dependent survival signals by caspase-mediated inactivation of RIP.

FEBS Lett 468:134-6 (2000)

PMID:11290317

Goyal L.

Cell death inhibition: keeping caspases in check.

Cell 104:805-8 (2001)

PMID:10195903

Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC.

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD.

Science 284:339-43 (1999)

PMID:14656699

Remillard CV, Yuan JX.

Activation of K+ channels: an essential pathway in programmed cell death.

Am J Physiol Lung Cell Mol Physiol 286:L49-67 (2004)

PMID:9670005

Gross A, Jockel J, Wei MC, Korsmeyer SJ.

Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis.

EMBO J 17:3878-85 (1998)