Entry Name Apoptosis - Nestor notabilis (Kea)
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 deathBRITE hierarchy
Pathway map Other DBs Organism Nestor notabilis (Kea) [GN:
nnt ]
Gene 104399557 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
104400216 EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237 ]
104400634 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
104401002 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
104403579 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
104404031 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
104404492 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
104406104 CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467 ] [EC:2.7.11.10 ]
104407157 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
104407830 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
104408103 PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131 ]
104408510 PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
104409749 DFFB; DNA fragmentation factor subunit beta [KO:K02311 ] [EC:3.-.-.-]
104410165 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
104410242 PTPN13; tyrosine-protein phosphatase non-receptor type 13 [KO:K02374 ]
104410411 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
104410866 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
104412975 ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
104413012 AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727 ] [EC:1.-.-.-]
104413443 FAS; LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Savitskaya MA, Onishchenko GE
Title Mechanisms of Apoptosis.
Journal Reference Authors Schleich K, Lavrik IN
Title Mathematical modeling of apoptosis.
Journal Reference Authors Lavrik I, Golks A, Krammer PH
Title Death receptor signaling.
Journal Reference Authors Jin Z, El-Deiry WS
Title Overview of cell death signaling pathways.
Journal Reference Authors Benn SC, Woolf CJ
Title Adult neuron survival strategies--slamming on the brakes.
Journal Reference Authors Orrenius S, Zhivotovsky B, Nicotera P
Title Regulation of cell death: the calcium-apoptosis link.
Journal Reference Authors Clarke P, Tyler KL
Title Apoptosis in animal models of virus-induced disease.
Journal Reference Authors Wen X, Lin ZQ, Liu B, Wei YQ
Title Caspase-mediated programmed cell death pathways as potential therapeutic targets in cancer.
Journal Reference Authors Shalini S, Dorstyn L, Dawar S, Kumar S
Title Old, new and emerging functions of caspases.
Journal Reference Authors Philchenkov A
Title Caspases: potential targets for regulating cell death.
Journal Reference Authors Stroh C, Schulze-Osthoff K
Title Death by a thousand cuts: an ever increasing list of caspase substrates.
Journal 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 Reference Authors Parsons MJ, Green DR
Title Mitochondria in cell death.
Journal Reference Authors Strasser A
Title The role of BH3-only proteins in the immune system.
Journal Reference Authors Schonthal AH
Title Endoplasmic reticulum stress: its role in disease and novel prospects for therapy.
Journal Reference Authors Malhi H, Kaufman RJ
Title Endoplasmic reticulum stress in liver disease.
Journal Reference Authors Malhotra JD, Kaufman RJ
Title The endoplasmic reticulum and the unfolded protein response.
Journal Reference Authors Wu J, Kaufman RJ
Title From acute ER stress to physiological roles of the Unfolded Protein Response.
Journal Reference Authors Repnik U, Stoka V, Turk V, Turk B
Title Lysosomes and lysosomal cathepsins in cell death.
Journal Reference Authors Cesen MH, Pegan K, Spes A, Turk B
Title Lysosomal pathways to cell death and their therapeutic applications.
Journal Reference Authors Dashzeveg N, Yoshida K
Title Cell death decision by p53 via control of the mitochondrial membrane.
Journal Reference Authors Bouchier-Hayes L, Green DR
Title Caspase-2: the orphan caspase.
Journal 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 Reference Authors Aggarwal BB
Title Signalling pathways of the TNF superfamily: a double-edged sword.
Journal 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 Reference Authors Dragovich T, Rudin CM, Thompson CB
Title Signal transduction pathways that regulate cell survival and cell death.
Journal Reference Authors Sofroniew MV, Howe CL, Mobley WC
Title Nerve growth factor signaling, neuroprotection, and neural repair.
Journal Reference Authors Kristiansen M, Ham J
Title Programmed cell death during neuronal development: the sympathetic neuron model.
Journal Reference Authors Logue SE, Martin SJ
Title Caspase activation cascades in apoptosis.
Journal Reference Authors Boivin WA, Cooper DM, Hiebert PR, Granville DJ
Title Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma.
Journal Reference Authors Cullen SP, Brunet M, Martin SJ
Title Granzymes in cancer and immunity.
Journal Reference Authors Liu K, Lan D, Li C, Liu S, Dai X, Song T, Wang X, Kong Q, He Z, Tan J, Zhang J
Title A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.
Journal Related nnt04141 Protein processing in endoplasmic reticulum
KO pathway
