3.4.22.55: caspase-2
This is an abbreviated version!
For detailed information about caspase-2, go to the full flat file.
Word Map on EC 3.4.22.55
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3.4.22.55
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caspases
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bcl-2
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necrosis
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bid
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proapoptotic
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anti-apoptotic
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parp
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raidd
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apoptosis-inducing
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caspase-dependent
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z-vad-fmk
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p53-induced
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tunel
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jurkat
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polyadp-ribose
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casps
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mitochondria-mediated
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non-apoptotic
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pan-caspase
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apaf-1
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apoptosome
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caspase-mediated
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death-inducing
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cpp32
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fasl
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z-devd-fmk
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executioner
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xiap
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damage-induced
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etoposide-induced
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anti-fas
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prodomains
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p53-dependent
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trail-induced
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executor
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bh3-only
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ac-devd-cho
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apoptogenic
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trail-mediated
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procaspase
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caspase-10
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chk1
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beta-converting
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mitochondria-dependent
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medicine
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diagnostics
- 3.4.22.55
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caspases
- bcl-2
- necrosis
- bid
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proapoptotic
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anti-apoptotic
- parp
- raidd
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apoptosis-inducing
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caspase-dependent
- z-vad-fmk
-
p53-induced
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tunel
-
jurkat
-
polyadp-ribose
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casps
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mitochondria-mediated
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non-apoptotic
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pan-caspase
- apaf-1
- apoptosome
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caspase-mediated
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death-inducing
- cpp32
- fasl
- z-devd-fmk
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executioner
- xiap
-
damage-induced
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etoposide-induced
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anti-fas
- prodomains
-
p53-dependent
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trail-induced
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executor
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bh3-only
- ac-devd-cho
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apoptogenic
-
trail-mediated
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procaspase
- caspase-10
- chk1
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beta-converting
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mitochondria-dependent
- medicine
- diagnostics
Reaction
strict requirement for an Asp residue at P1, with Asp316 being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp-/- =
Synonyms
AjCASP, C14.006, CASP-2, Casp2, caspase 2, caspase-2, caspase-2L, caspase-2S, ICH-1, ICH-1 protease, ICH-1L/1S, NEDD-2
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General Information
General Information on EC 3.4.22.55 - caspase-2
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evolution
malfunction
metabolism
physiological function
additional information
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caspase-2 is an evolutionarily conserved caspase with features of both initiator and executioner caspases
evolution
caspase-2 is the most evolutionarily conserved member in the human caspase family
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Casp2-null animals develop normally, and thymocytes and neurons derived from them seem to undergo similar levels of apoptosis to those from wild-type littermates. Nevertheless, several subtle phenotypes are associated with the Casp2-knockout mice: Casp2-knockout females have a slight increase in the number of oocytes and Casp2/ oocytes show reduced apoptosis in response to treatment with doxorubicin. The neurons derived from Casp2-null mice are resistant to beta-amyloid-mediated death, which suggests a role for caspase 2 in neuronal death. Casp2-deficient mice also show signs of premature ageing, including accumulation of oxidative damage. Mouse embryonic fibroblasts from Casp2-deficient animals show a reduced or delayed apoptotic response to some cytotoxic drugs, have an aberrant DNA damage and cell cycle response and are readily transformed when they are challenged by oncogene expression.
malfunction
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caspase-2 knockout mice do not develop early spontaneous tumors, but loss of caspase-2 in mice is associated with accelerated tumorigenesis driven by transgenic c-Myc on the mu-enhancer, thus caspase-2-deficient embryonic fibroblasts are more efficiently transformed than wild-type cells. Caspase-2-deficient mice have features consistent with accelerated ageing, phenotype, overview
malfunction
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decreased caspase-2 and RAIDD expression is observed in mantle cell lymphoma tumor samples. In addition, drug resistance in childhood forms of acute lymphoblastic leukemia is correlated with decreased levels of caspase-2. In contrast, increased levels of caspase-2 in acute myelogenous leukemia and adult ALL are associated with decreased patient survival. Possibly inactivation of caspase-2 in tumors occurs through disruption of the pathway through mutation or improper regulation of a protein that regulates caspase-2 activity
malfunction
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depletion of caspase-2 prevents p21 expression and thereby reverts the gamma-IR-induced senescent phenotype of wild-type HCT116 colon carcinoma cells into apoptosis, knockdown of none of the caspase-2-interacting components RAIDD, RIP or DNA-PKcs is able to mimic these processes, but knockdown of caspase-2 specifically impairs DNA damage-induced p21 expression, and silencing of caspase-2 impairs exogenous expression of p21 constructs containing 3'-UTR sequences, whereas overexpression of a caspase-2 mutant increases p21 levels. Silencing of caspase-2 impairs exogenous expression of p21 constructs containing 3'-UTR sequences
malfunction
cells lacking caspase-2 are protected from cell death induced by Staphylococcus aureus alpha-toxin
malfunction
down-regulation or inactivation of caspase-2 blocks amyloid beta-mediated effects on primary hippocampal cultures
malfunction
down-regulation or inactivation of caspase-2 blocks amyloid beta-mediated effects on primary hippocampal cultures
malfunction
maturation, activation, and cytokine secretion are significantly impaired in Caspase-2 knockout cells infected with Brucella abortus strain RB51 or Salmonella typhimurium strain SL1344
malfunction
the loss of caspase-2 in mice results in an osteopenic phenotype associated with increased numbers of osteoclasts in vivo. Mitochondrial reactive oxygen species are significantly increased in caspase-deficient precursors after receptor activator of nuclear factor kappa-B ligand administration
malfunction
both pharmacological inhibition and shRNA-mediated knockdown of caspase-2 suppresses myogenic differentiation and dramatically impaired myotube formation
malfunction
caspase-2 deficiency leads to increased cellular stress largely because these mice fail to respond to oxidative stress by upregulating their antioxidant defense mechanism
malfunction
decreasing the levels of caspase-2 restores long-term memory in mice that have existing deficits
malfunction
loss of caspase-2 leads to an acceleration of tumor onset in the Emü-Myc mouse lymphoma model
malfunction
loss of caspase-2 leads to enhanced tumor proliferation and progression
caspase-2 is a critical mediator in the activation of the RhoA/ROCK-II signaling pathway, leading to the collapse of dendritic spines. Inactive RhoA-GDP but not active RhoA-GTP forms a complex with caspase-2
metabolism
caspase-2 is a critical mediator in the activation of the RhoA/ROCK-II signaling pathway, leading to the collapse of dendritic spines. Inactive RhoA-GDP but not active RhoA-GTP forms a complex with caspase-2
metabolism
caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, DELTAtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with Alzheimer's disease
metabolism
caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, DETAtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with Alzheimer's disease
apoptosis induced by doxorubicin and 5-fluorouracil is caspase-2-dependent
physiological function
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caspase 2 represses transcription of the survivin gene, a general regulator of cell division and cytoprotection in tumors. This pathway involves caspase 2 proteolytic cleavage of the nuclearfactor kappaB (NFkappaB) activator, RIP1. Loss of RIP1 abolishes transcription of NFkappaB target genes, including survivin, resulting in deregulated mitotic transitions, enhanced apoptosis and suppression of tumorigenicityin vivo. Caspase 2 functions as an endogenous inhibitor of NFkappaB-dependent cell survival.
physiological function
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caspase-2 activation is commonly associated with induction of IFN-beta-induced apoptosis in IFN-beta-sensitive melanoma cells
physiological function
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caspases-2 and -8 are involved in the presenilin1/gamma-secretase-dependent cleavage of amyloid precursor protein after the induction of apoptosis
physiological function
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critical role of caspase-2 in mediating rough Brucella abortus induced macrophage cell death
physiological function
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discussion of the role of caspase-2 and potential contribution of the enzyme to the pathology of human diseases
physiological function
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overview on the function of caspase-2 in cell death signaling
physiological function
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The increased expression of PIDD (p53-induced protein with a death domain) induced by p53 forms a complex with RAIDD and caspase-2 (termed a PIDDosome), which activates the protease. The processed caspase-2 acts as a canonical caspase in the mitochondrial-mediated pathway triggering cytochrome c release. Once released to the cytoplasm, cytochrome c binds to APAF-1 to form a wheel-like complex, the apoptosome, resulting in the activation of caspase-9 and subsequent cleavage of downstream caspases including caspase-3.
physiological function
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caspase-2 is commonly required for DNA damage-induced p21 expression. Caspase-2 regulates p21 expression at the translational level, independently of its enzymatic activity but also not requiring known caspase-2-activating platforms
physiological function
caspase-2 plays important roles in stress-induced apoptosis, cell cycle regulation, and tumor suppression
physiological function
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role of caspase-2 in apoptosis, and caspase-2 may act as a tumor suppressor, mechanisms through which caspase-2 signals, e.g. involving PIDD, also known as LRDD or leucine-rich repeat and death domain-containing protein, caspase-2 pathways to apoptosis and cell cycle arrest, detailed overview. PIDD activation and more importantly caspase-2 activation is not always synonymous with induction of apoptosis, a threshold of caspase-2 activation must be reached before caspase-2-dependent apoptosis is engaged. Cleavage of Mdm2 is not the sole way caspase-2 can induce growth arrest
physiological function
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role of caspase-2 in apoptosis, and caspase-2 may act as a tumor suppressor, mechanisms through which caspase-2 signals, e.g. involving PIDD, also known as LRDD or leucine-rich repeat and death domain-containing protein, caspase-2 pathways to apoptosis and cell cycle arrest, detailed overview. PIDD activation and more importantly caspase-2 activation is not always synonymous with induction of apoptosis, a threshold of caspase-2 activation must be reached before caspase-2-dependent apoptosis is engaged. Cleavage of Mdm2 is not the sole way caspase-2 can induce growth arrest
physiological function
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upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a positive feedback loop that inhibits Mdm2, a key negative regulator of p53, and reinforces p53 stability and activity, contributing to cell survival and drug resistance, mechanism of Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress, overview
physiological function
Brucella abortus strain RB51- and S2308-induced BMDC cell death is regulated by caspase-2. The enzyme is required for naive T-lymphocyte proliferation following stimulation with RB51-infected bone marrow-derived dendritic cells
physiological function
caspase-2 is implicated in the regulation of cell death that is induced by metabolic imbalance, DNA damage, endoplasmic reticulum (ER) stress, mitotic catastrophe and others. Caspase-2 is implicated in the induction of cell death by pathogenic bacteria, such as Brucella, Staphylococcus aureus and Salmonella. Caspase-2 is controlling aging and cell death in response to DNA damage. The enzyme is also linked to cell death that is induced by aberrant mitosis in cancer cells that transiently arrest in prometaphase after cell fusion. Caspase 2 is crucial for oocyte apoptosis
physiological function
caspase-2 is involved in apoptosis, nuclear factor-kappaB regulation, and tumor suppression. Caspase-2 catalytic site Cys-320 and Ser-139 residues are required for caspase-2 to suppress tumorigenesis in nude mice
physiological function
caspase-2 modulates osteoclastogenesis through down-regulating oxidative stress
physiological function
caspase-2 plays a critical role in mediating the synaptic changes and memory alteration induced by amyloid beta in Alzheimer's disease
physiological function
caspase-2 plays a critical role in mediating the synaptic changes and memory alteration induced by amyloid beta in Alzheimer's disease
physiological function
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caspase-2 plays a role in lipoapoptosis and is required for cell death
physiological function
in epithelial cells, caspase-2 is activated as an initiator caspase in a PIDDosome-independent manner to regulate pore-forming toxin-mediated cell death
physiological function
the enzyme is essential for c-Jun transcriptional activation and Bim induction in in neurons subjected to apoptotic stimuli
physiological function
the enzyme is implicated in tumor suppression and plays a role in regulating the cellular response towards oxidative stress. Key cellular processes such as proliferation, aging, maintenance of genome surveillance and the redox system are affected by caspase-2 function
physiological function
the long isoform, casp-2L, promotes apoptosis, whereas the short isoform, casp-2S, inhibits apoptosis. Isoform casp-2S is responsible for inhibiting DNA damage-induced cytoplasmic fodrin cleavage independent of cellular p53 status, and prevents cisplatin-induced membrane blebbing thereby affecting cellular apoptosis
physiological function
caspase-2 acts as a tumor suppressor. Loss of caspase-2 leads to an acceleration of tumor onset in the EMy-Myc mouse lymphoma model
physiological function
caspase-2 functions as a tumor suppressor in Kras-driven lung cancer in vivo. Caspase-2 cleaves and inhibits Mdm2 and thereby promotes the stability of the tumor-suppressor p53
physiological function
caspase-2 is required for skeletal muscle differentiation and myogenesis. The role of caspase-2 is to regulate p21 induction at the onset of differentiation, which may regulate the myogenic program
physiological function
the enzyme is essential for mitochondrial oxidative stress-induced apoptosis
physiological function
the enzyme may be involved in invertebrate immune response, especially in eliminating and degrading invading pathogens
physiological function
the enzyme mediates site-specific retinal ganglion cell death after blunt ocular injury
physiological function
the enzyme protects against oxidative stress in vivo
caspase-2 is synthesized as an inactive zymogen. The zymogen sequence includes a long prodomain containing a CARD followed by a large domain, a linker, and a small domain. Caspase-2 undergoes autocatalytic activation to remove the prodomain and linker region to generate a stable dimer consisting of the large subunit p19 and the small subunit p12. This p19/p12 dimer self-associates to form the active caspase-2
additional information
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caspase-2 is synthesized as an inactive zymogen. The zymogen sequence includes a long prodomain containing a CARD followed by a large domain, a linker, and a small domain. Caspase-2 undergoes autocatalytic activation to remove the prodomain and linker region to generate a stable dimer consisting of the large subunit p19 and the small subunit p12. This p19/p12 dimer self-associates to form the active caspase-2