Entry
Name
Apoptosis - Hippoglossus stenolepis (Pacific halibut)
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
Ortholog table
Other DBs
Organism
Hippoglossus stenolepis (Pacific halibut) [GN:
hsp ]
Gene
118098522 tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
118116455 tumor necrosis factor ligand superfamily member 10-like [KO:K04721 ]
118125828 tnfrsfa; tumor necrosis factor receptor superfamily, member a [KO:K04722 ]
118121152 faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
118119490 fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
118113213 tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
118109955 tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
118120504 prkra; interferon-inducible double-stranded RNA-dependent protein kinase activator A homolog isoform X1 [KO:K04398 ] [EC:3.4.22.61 ]
118113980 mcl1b; induced myeloid leukemia cell differentiation protein Mcl-1b [KO:K02539 ]
118125441 sptan1; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114 ]
118111089 dffb; DNA fragmentation factor subunit beta [KO:K02311 ] [EC:3.-.-.-]
118122630 aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727 ] [EC:1.-.-.-]
118104834 itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
118105042 inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
118109898 itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959 ]
118099915 eif2s1b; eukaryotic translation initiation factor 2 subunit 1b [KO:K03237 ]
118116537 atf4a; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
118122602 birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060 ]
118125425 june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
118116236 nfkbiab; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha b [KO:K04734 ]
118125641 ptpn13; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374 ]
118098216 gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402 ]
118098217 growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
118115579 gadd45ga; growth arrest and DNA-damage-inducible, gamma a [KO:K04402 ]
118115882 growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
118118323 gadd45aa; growth arrest and DNA-damage-inducible, alpha, a [KO:K04402 ]
118121000 gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402 ]
118121018 growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
118106261 pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
118111369 pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
118114686 phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649 ]
118117905 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
118117936 pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
118120979 pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649 ]
118125392 pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
118120902 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
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
Related pathway
hsp04141 Protein processing in endoplasmic reticulum
KO pathway
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