Entry
Name
Apoptosis - Xenopus laevis (African clawed frog)
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
Other DBs
Organism
Xenopus laevis (African clawed frog) [GN:
xla ]
Gene
100137626 tnfrsf1a.S; TNF receptor superfamily member 1A S homeolog precursor [KO:K03158 ]
100192362 mcl1.L; MCL1, BCL2 family apoptosis regulator L homeolog [KO:K02539 ]
101027271 gadd45b.S; growth arrest and DNA damage inducible beta S homeolog [KO:K04402 ]
108696066 tnfrsf1a.L; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
108696357 dffa.L; DNA fragmentation factor subunit alpha isoform X2 [KO:K02310 ]
108697677 dffb.S; DNA fragmentation factor subunit beta [KO:K02311 ] [EC:3.-.-.-]
108698277 aifm1.L; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727 ] [EC:1.-.-.-]
108699293 eif2s1.L; eukaryotic translation initiation factor 2 subunit 1 isoform X2 [KO:K03237 ]
108700339 mcl1.S; induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539 ]
108701211 ern1.L; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852 ] [EC:2.7.11.1 3.1.26.-]
108701437 cflar.L; CASP8 and FADD-like apoptosis regulator isoform X2 [KO:K04724 ]
108702862 ern1.S; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852 ] [EC:2.7.11.1 3.1.26.-]
108704383 bid.L; BH3-interacting domain death agonist isoform X1 [KO:K04726 ]
108706884 pik3r2.S; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
108708728 parp4.1.L; protein mono-ADP-ribosyltransferase PARP4 isoform X1 [KO:K10798 ] [EC:2.4.2.-]
108712402 gadd45b.L; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
108713027 pik3r2.L; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
108713866 pidd1.L; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130 ]
108714209 gadd45a.L; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402 ]
108714562 csf2rb.L; cytokine receptor common subunit beta isoform X1 [KO:K04738 ]
108715004 faslg.S; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
108717006 tnfsf10.L; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
108717120 pik3cb.L; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
108718090 pik3ca.S; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
108718190 pik3cb.S; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
373637 bax.S; BCL2-associated X protein L homeolog [KO:K02159 ]
373718 sptan1.L; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114 ]
373724 sptan1.S; spectrin alpha chain, non-erythrocytic 1 isoform X1 [KO:K06114 ]
373752 pik3ca.L; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
379224 gadd45a.S; growth arrest and DNA damage inducible alpha S homeolog [KO:K04402 ]
379285 gadd45g.S; uncharacterized protein LOC379285 [KO:K04402 ]
379748 tuba1cl.3.L; tubulin alpha chain 1c like, L homeolog [KO:K07374 ]
379991 map2k1.L; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368 ] [EC:2.7.12.2 ]
380444 eif2s1.S; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237 ]
394353 rela.L; putative transcription factor p65 homolog [KO:K04735 ]
394382 birc5.S; baculoviral IAP repeat-containing protein 5.1-A [KO:K08731 ]
397771 kras.L; kirsten rat sarcoma viral oncogene homolog L homeolog [KO:K07827 ]
397931 tubal3.1.L; tubulin alpha like 3, gene 1 L homeolog [KO:K07374 ]
398418 birc5.L; baculoviral IAP repeat-containing protein 5.1-B [KO:K08731 ]
398454 birc5l.L; baculoviral IAP repeat-containing protein 5.2-B [KO:K08731 ]
398615 ddit3.L; DNA damage inducible transcript 3 L homeolog [KO:K04452 ]
398804 atf4.L; activating transcription factor 4 L homeolog [KO:K04374 ]
399196 gadd45g.L; growth arrest and DNA damage inducible gamma L homeolog [KO:K04402 ]
399202 pik3r1.S; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
399254 itpr1.S; inositol 1,4,5-trisphosphate receptor type 1 S homeolog [KO:K04958 ]
399406 hras.L; Harvey rat sarcoma viral oncogene homolog L homeolog [KO:K02833 ]
403386 eif2ak3.S; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860 ] [EC:2.7.11.1 ]
404688 tnfrsf10b.L; tumor necrosis factor receptor superfamily member 10b L homeolog precursor [KO:K04722 ]
431994 tubal3.1.S; tubulin alpha like 3, gene 1 S homeolog [KO:K07374 ]
432200 ikbkb.L; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta L homeolog [KO:K07209 ] [EC:2.7.11.10 ]
443565 ptpn13.L; tyrosine-protein phosphatase non-receptor type 13 isoform X1 [KO:K02374 ]
443964 pik3r1.L; phosphoinositide-3-kinase regulatory subunit 1 L homeolog [KO:K02649 ]
444075 ern2.S; endoplasmic reticulum to nucleus signaling 2 S homeolog precursor [KO:K08852 ] [EC:2.7.11.1 3.1.26.-]
444261 apaf1.L; apoptotic peptidase activating factor 1 L homeolog [KO:K02084 ]
446279 daxx.L; death-associated protein 6 L homeolog [KO:K02308 ]
446370 parp2.S; poly(ADP-ribose) polymerase 2 S homeolog [KO:K28005 ]
446568 birc2.L; baculoviral IAP repeat containing 2 L homeolog [KO:K16060 ]
446786 pik3r3.S; phosphoinositide-3-kinase regulatory subunit 3 S homeolog [KO:K02649 ]
446833 nfkbia.L; NFKB inhibitor alpha L homeolog [KO:K04734 ]
447201 fos.S; FBJ murine osteosarcoma viral oncogene homolog S homeolog [KO:K04379 ]
447594 pik3r3.L; phosphoinositide-3-kinase regulatory subunit 3 L homeolog [KO:K02649 ]
447632 nfkb1.L; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 L homeolog [KO:K02580 ]
495479 csf2rb.S; colony stimulating factor 2 receptor beta common subunit S homeolog precursor [KO:K04738 ]
496021 tuba1l.S; tubulin alpha 1 like S homeolog [KO:K07374 ]
496154 parp3.L; poly(ADP-ribose) polymerase family member 3 L homeolog [KO:K10798 ] [EC:2.4.2.-]
496403 fadd.S; Fas associated via death domain S homeolog [KO:K02373 ]
724076 bid.S; BH3 interacting domain death agonist S homeolog [KO:K04726 ]
733418 tradd.L; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
734165 atf4.S; activating transcription factor 4 S homeolog [KO:K04374 ]
734297 nfkbia.S; uncharacterized protein LOC734297 [KO:K04734 ]
734644 bak1.S; BCL2 antagonist/killer 1 S homeolog [KO:K14021 ]
735055 birc5l.S; baculoviral IAP repeat containing 5 like S homeolog [KO:K08731 ]
735069 ikbkg.L; inhibitor of nuclear factor kappa B kinase subunit gamma L homeolog [KO:K07210 ]
780745 cflar.S; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
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 pathway
xla04141 Protein processing in endoplasmic reticulum
KO pathway