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Information on EC 3.4.22.64 - caspase-11 and Organism(s) Mus musculus and UniProt Accession P70343
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3.4.22.64 caspase-11Specify your search results
Word Map
- 3.4.22.64
- inflammasome
-
pyroptosis
- lps
- lipopolysaccharide
-
non-canonical
-
gasdermin
- sepsis
-
gsdmd
- interleukin-1
-
lps-induced
- pyrin
-
casp11
-
apoptosis-associated
-
nod-like
- caspase-5
-
pore-forming
-
speck-like
-
guanylate-binding
-
inflammasome-mediated
- wedelolactone
- rodentium
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pyroptosis-related
-
inflammasome-dependent
-
caspase-1/11
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caspase-1-mediated
-
bmdms
-
speck
- thailandensis
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
strict requirement for Asp at the P1 position and has a preferred cleavage sequence of (Ile/Leu/Val/Phe)-Gly-His-Asp-/-
Synonyms
caspase-11, casp4, caspase 11, ich-3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C14.012
-
-
-
-
caspase-11
ICH-3 protease
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
-
-
CAS REGISTRY NUMBER
COMMENTARY
216503-96-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
acetyl-VEHD + 7-amino-4-methylcoumarin
-
-
-
-
?
cationic channel subunit transient receptor potential channel 1 + H2O
?
-
-
-
-
?
cationic channel subunit transient receptor potential channel 1 + H2O
?
-
i.e. TRPC1, plays a role in regulating innate immunity by modulating channel complexes during inflammatory responses
-
-
?
procaspase-3 + H2O
?
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3
-
-
?
additional information
?
-
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
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-
?
additional information
?
-
-
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
-
-
?
additional information
?
-
-
optimal cleavage site is IEHD, LEHD, VEHD or PEHD
-
-
?
additional information
?
-
-
phenotype of animals deficient in caspase-11: resistant to lipopolysaccharide-induced caspase-1 processing, interleukin-1alpha and interleukin-beta secretion, and endotoxic shock
-
-
?
additional information
?
-
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3. The enzyme is an upstream activator of caspase-1. Caspase-11 deficient animals have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion. The enzyme is A VERY IMPORTANT REGULATOR OF APOPTOSIS
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-
?
additional information
?
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-
pro-caspase-11 physically interacts with pro-ICE in cells, the expression of casp-11 is essential for activation of ICE. Caspase-11 is a compinent of ICE complex and is required for the activation of ICE. Important role of ICE and caspase-11 in mediating apoptosis in pathological conditions
-
-
?
additional information
?
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-
the enzyme is involved in cytokine activation
-
-
?
additional information
?
-
-
C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation
-
-
?
additional information
?
-
-
caspase-11 has a regulatory role in ethanol-induced apoptosis. Suppression of caspase-11 expression may be a mechanism by which Scutellariae radix (Chinese herbal medicine) exerts its cytoprotective effect
-
-
?
additional information
?
-
-
neurotoxic effects of lipopolysaccharide on nigral dopaminergic neurons are mediated by microglial activation, interleukin-1beta, and expression of caspase-11 in mice
-
-
?
additional information
?
-
-
neurotoxicity of 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine may be mediated via activation of the caspase-11 cascade and inflammatory cascade, as well as the mitochondrial apoptotic cascade
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-
?
additional information
?
-
-
a pathway modulating inflammatory-cell migration involve caspase-11 and actin interacting protein 1
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-
?
additional information
?
-
-
caspase-11 may be a central regulator of multiple events, including cell migration, cytokine maturation and apoptosis, during inflammation responses. Caspase-11 interacts physically and functionally with actin interacting protein 1, an activator of cofilin-mediated actin depolymerization. Caspase-11 and actin interacting protein 1 work cooperatively to promote cofilin-mediated actin depolymerization
-
-
?
additional information
?
-
-
Flightless-I regulates the subcellular distribution of caspase-11 by promoting its localization at the cell leading edge
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
cationic channel subunit transient receptor potential channel 1 + H2O
?
-
i.e. TRPC1, plays a role in regulating innate immunity by modulating channel complexes during inflammatory responses
-
-
?
procaspase-3 + H2O
?
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3
-
-
?
additional information
?
-
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
-
-
?
additional information
?
-
-
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
-
-
?
additional information
?
-
-
phenotype of animals deficient in caspase-11: resistant to lipopolysaccharide-induced caspase-1 processing, interleukin-1alpha and interleukin-beta secretion, and endotoxic shock
-
-
?
additional information
?
-
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3. The enzyme is an upstream activator of caspase-1. Caspase-11 deficient animals have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion. The enzyme is A VERY IMPORTANT REGULATOR OF APOPTOSIS
-
-
?
additional information
?
-
-
pro-caspase-11 physically interacts with pro-ICE in cells, the expression of casp-11 is essential for activation of ICE. Caspase-11 is a compinent of ICE complex and is required for the activation of ICE. Important role of ICE and caspase-11 in mediating apoptosis in pathological conditions
-
-
?
additional information
?
-
-
the enzyme is involved in cytokine activation
-
-
?
additional information
?
-
-
C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation
-
-
?
additional information
?
-
-
caspase-11 has a regulatory role in ethanol-induced apoptosis. Suppression of caspase-11 expression may be a mechanism by which Scutellariae radix (Chinese herbal medicine) exerts its cytoprotective effect
-
-
?
additional information
?
-
-
neurotoxic effects of lipopolysaccharide on nigral dopaminergic neurons are mediated by microglial activation, interleukin-1beta, and expression of caspase-11 in mice
-
-
?
additional information
?
-
-
neurotoxicity of 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine may be mediated via activation of the caspase-11 cascade and inflammatory cascade, as well as the mitochondrial apoptotic cascade
-
-
?
additional information
?
-
-
a pathway modulating inflammatory-cell migration involve caspase-11 and actin interacting protein 1
-
-
?
additional information
?
-
-
caspase-11 may be a central regulator of multiple events, including cell migration, cytokine maturation and apoptosis, during inflammation responses. Caspase-11 interacts physically and functionally with actin interacting protein 1, an activator of cofilin-mediated actin depolymerization. Caspase-11 and actin interacting protein 1 work cooperatively to promote cofilin-mediated actin depolymerization
-
-
?
additional information
?
-
-
Flightless-I regulates the subcellular distribution of caspase-11 by promoting its localization at the cell leading edge
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
benzene, increase of caspase-4 expression after 12 days of oral benzene treatment to p53KO mice
-
additional information
-
activation through dimerization. Signaling pathways involved in caspase-11 activation, overview
-
additional information
-
Bacterial infection triggers caspase-11 activation , and intracellular lipopolysaccharide triggers caspase-11 activation, Toll-like receptor 4 is dispensable for caspase-11 triggering by cytoplasmic lipopolysaccharide, mechanism, detailed overview
-
additional information
-
caspase-11 is activated by a cytosolic sensing mechanism that detects bacterial-derived signals delivered into the host cytosol through the type IV secretion apparatus. Caspase-11 activation by Legionella pneumophila has distinct kinetic and molecular parameters, overview. Caspase-11 activation requires upstream protein(s) capable of sensing a microbial or endogenous danger signal. Caspase-11 requires type I IFN production mediated by TRIF-dependent TLR signaling. And caspase-1 is dispensable for caspase-11-dependent pyroptosis induced by Legionella pneumophila
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additional information
-
the adaptor protein TRIF upregulates procaspase-11 expression, and this upregulation is required for caspase-11 processing and activation. Lipopolysaccharide treatment or type I IFN treatment alone does not cause caspase-11-dependent cell death
-
additional information
-
the cholera toxin B subunit and many different Gram-negative bacteria can trigger Caspase-11 activation in vitro. Cytosolic infection of cells with Burkholderia species and cytyosolic mutants of Salmonella typhimurium and Legionella pneumophila trigger the enzyme
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
caspase-11 is upregulated in a subpopulation of cells i brain after ischemic injury
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the highest expression levels of murine Casp11 gene are observed in spleens
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
Flightless-I regulates the subcellular distribution of caspase-11 by promoting its localization at the cell leading edge
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
caspase-11 auto-cleavage at the intersubunit linker is essential for optimal catalytic activity and subsequent proteolytic cleavage of gasdermin D. Macrophages from caspase-11-processing dead KI mice (Casp11Prc D285A/D285A) exhibit defective caspase-11 auto-processing and phenocopy Casp11-/- and caspase-11 enzymatically dead KI (Casp11Enz C254A/C254A) macrophages in attenuating responses to cytoplasmic lipopolysaccharide or Gram-negative bacteria infection. Gasdermin D D276A/D276A KI macrophages also fail to cleave gasdermin D and are hyporesponsive to inflammasome stimuli
physiological function
evolution
malfunction
metabolism
physiological function
additional information
-
caspase-11 cooperatively interacts with actin-interacting protein to activate cofilin-dependent actin depolymerization leading to increased splenocyte migration, caspase-11-mediated actin depolymerization appears to be independent of its enzymatic activity. Caspase-1, -2, -4, -9, and -11 have particularly long pro-domains that contain either death effector domains (DED) or caspase recruitment domains (CARD), which are thought to confer specificity of activation since they mediate interactions with other DED- and CARD-containing adaptor proteins. Association with these adaptor proteins likely nucleates caspases, increasing their local concentration. This nucleation can favor activation through dimerization
physiological function
Casp11-/- mice are highly susceptible to the azoxymethane dextran sulfate sodium model of colitis-associated cancer, compared to their wild-type littermates. Deficient IL-18 production occurs at initial inflammation stages of disease, and IL-1beta production is more significantly impaired in Casp11-/- colons during established colitis-associated cancer. Casp11-/- colons display defective STAT1 activation during disease progression, and IL-1beta signalling induces caspase-11 expression and STAT1 activation in primary murine macrophages and intestinal epithelial cells
physiological function
caspase-1 and caspase-11 display differential roles in response to infection with the fungal pathogen Aspergillus fumigatus. Casp11-/- mice are more susceptible to infection with Aspergillus fumigatus conidia compared with wild-type mice. Casp11-/- mice succumb to infection with a delayed kinetic compared with Casp1Null mice or Casp1-/- Casp11-/- mice. Caspase-11 has no role in the activation of the inflammasome in bone marrow-derived dendritic cells in response to A. fumigatus, but contributes to the host defense against A. fumigatus infection in vivo
physiological function
caspase-11 cleaves gasdermin D, and the resulting amino-terminal fragment promotes both pyroptosis and NLRP3-dependent activation of caspase-1 in a cell-intrinsic manner. Gasdermin D is essential for caspase-11-dependent pyroptosis and interleukin-1beta maturation. Macrophages from gasdermin-/- mice exhibit defective pyroptosis and interleukin-1beta secretion induced by cytoplasmic lipopolysaccharide or Gram-negative bacteria. Gasdermin-/- mice are protected from a lethal dose of lipopolysaccharide
physiological function
caspase-11 deficiency shows the same effect as the combined absence of both caspase-1 and caspase-11 on oviduct pathology. Caspase-11-deficient mice show reduced dilation in both the oviducts and uterus. In the caspase-11-deficient mice, increased chlamydial burdens are observed in the upper genital tract, which correlate with increased CD4 T cell recruitment. There are significantly fewer neutrophils in the oviducts of caspase-11-deficient mice
physiological function
in response to corneal infection with Aspergillus fumigatus, caspase-11-/- mice exhibit the same susceptibility phenotype as IL-1beta-/-, ASC-/-, NLRP3-7-, and caspase-1-/- mice, with impaired neutrophil recruitment to infected corneas and increased hyphal growth. Caspase-11 is required for caspase-1 activation and IL-1eta processing during infection. In vitro, caspase-11 is regulated by the common type I IFN receptor (IFNAR) through JAK-STAT signaling and caspase-11 is required for speck formation and caspase-1 activity
evolution
-
inflammatory caspases all share a similar prodomain at the N-terminus responsible for protein-protein interactions: the caspase activation and recruitment domain (CARD). The genes of the inflammatory caspases are all located adjacent to the Casp1 gene on the mammalian chromosome (chromosome 9 in mouse), forming an inflammatory gene cluster. The close proximity of these genes and the high degree of similarity in the caspase protein structures might explain that the multiple inflammatory caspases arose from amplification of the Casp1 gene locus in the early stages of mammalian evolution
malfunction
-
germline mutation of Casp11 in mouse strain 129 abolishes inflammasome activation by CTB. Strain 129 mice, like Casp11-/- mice, exhibits defects in IL-1beta production and harbours a mutation in the Casp11 locus that attenuates caspase-11 expression
malfunction
-
all Casp1-/- mice also lack caspase-11, due to the generation of the Casp1-/- line in the 129 mouse strain background, which express a mis-spliced and truncated version of the Casp11 messenger RNA
malfunction
-
all existing caspase-1 deficient mice also lack Caspase-11 due to the backcrossing of a mutant Casp11 allele from 129 into C57BL/6 mice
malfunction
-
Casp11-/- knockout mouse strains are resistant to developing lethal sepsis
malfunction
-
defects in the IFN-alpha/beta, but not IFN-gamma, pathways render macrophages severely impaired in processing of caspase-11 following infection with Salmonella typhimurium, EHEC or Citrobacter rodentium, while exogenous IFN-beta rescues caspase-11 processing in Trif-/- macrophages. The absence of the TRIF-IFNAR pathway abolishes both the expression and activation of caspase-11, and treatment of Trif-/- macrophages with IFN-beta or IFN-gamma restores both the precursor and cleaved forms of caspase-11
malfunction
-
upon infection with Salmonella typhimurium, the level of pro-interleukin-1beta maturation in bone marrow derived macrophages is reduced in the absence of caspase-11
metabolism
-
apoptosis is triggered by the initiator caspases, caspase-2, -8, -9, and -10, which subsequently activate the executioner caspases, caspase-3, -6, and -7
metabolism
-
Gram-negative bacteria and certain pore-forming toxins induce a caspase-11-dependent noncanonical inflammasome that contributes to NLRP3-dependent interleukin-1beta release and also triggers NLRP3- and caspase-1-independent cell death and interleukin-1alpha release
metabolism
-
Gram-negative bacteria are specifically detected via a surveillance mechanism that involves activation of extracellular receptors such as Toll-like receptors followed by intracellular recognition and activation of pathways such as caspase-11. Extracellular LPS primarily stimulates TLR4, which can serve as a priming signal for expression of inflammasome components. Intracellular LPS can then trigger caspase-11-dependent inflammasome activation in the cytoplasm. Bacterial infection triggers caspase-11 activation and leads to two distinct signals: (i) caspase-1-dependent interleukin-1beta/interleukin-18 secretion and caspase-1-independent pyroptosis
metabolism
-
while Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) that aberrantly enter the cytosol trigger Caspase-11, enhancing clearance of S. typhimurium sifA in vivo. This response does not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also trigger Caspase-11, protecting mice from lethal challenge with Burkholderia thailandensis and Burkholderia pseudomallei. Caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens
physiological function
-
caspase-11 mediates non-canonical inflammasome activation.Caspase-11 rather than caspase-1 is required for lipopolysaccharide-induced lethality. Interleukin-1beta secretion in response to other bacterial toxins, including adenylcyclase toxin, listeriolysin O toxin, or Clostridium difficile toxin B, is not affected by caspase-11 deficiency. Caspase-11 also is dispensable for NLRP3-dependent IL-1beta secretion in response to monosodium urate, calcium pyrophosphate, or the ionophore nigericin. In contrast, NLRP3- and ASC-dependent IL-1beta secretion from BMDMs infected with live Escherichia coli, Citrobacter rodentium and Vibriae cholerae, requires caspase-11, with or without lipopolysaccharide priming
physiological function
-
activated caspase-11 triggers cell death, caspase-11 is essential for the induction of endotoxic shock in vivo
physiological function
-
caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1beta secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide and Gram-negative bacteria. Caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1. Caspase-11 controls the TRPC1-dependent decrease in cytosolic Ca2+ following lipopolysaccharide treatment
physiological function
-
caspase-11 is an inflammatory caspase that can also promote interleukin-1beta secretion dependent upon NLRP3, ASC, and Caspase-1. Inflammatory caspase-11 triggers pyroptosis, a form of programmed cell death. The enzyme can be detrimental in inflammatory disease,but has no protective role during infection. Caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria
physiological function
-
caspase-11 is required for cofilin phosphorylation. Caspase-11-dependent cell death and interleukin-1beta secretion can only be detected in vitro in the absence of a NAIP/NLRC4 stimulus, e.g. flagellin. Caspase-11 is required for the release of the alarmins, interleukin-1alpha and HMGB1. The role of caspase-11 in pro-interleukin-18 and pro-interleukin-1beta maturation is dependent on NLRP3/ASC/CASP1 inflammasomes. Pro-inflammatory caspases play important roles in innate immunity. Caspase-11 contributes to host defenses against pathogen invasion. Caspase-11 functions and mechanisms of activation, overview
physiological function
-
caspase-11 plays a role in the inflammasome in the cytoplasm. Activation of inflammatory caspases, e.g. caspase-11, leads to the processing and maturation of inflammatory cytokines, such as interleukin-1beta and interleukin-18, as well as a specific form of cell death termed pyroptosis. Caspase-11 can induce cell death and form hetero-complexes with caspase-1. Caspase-11 by itself inefficiently cleaves pro-interleukin-1beta, suggesting early on that caspase-11 might rely on caspase-1 for cytokine maturation. The caspase-11 non-canonical inflammasome plays a significant role in Gram-negative bacterial infections, including Escherichia coli, Citrobacter rodentium, Shigella flexneri, Salmonella typhimurium, Legionella pneumophila, and Burkholderia thailandensis, caspase-11 can restrict the replication of intracellular pathogenic bacteria (Salmonella typhimurium and Burkholderia species)
physiological function
-
caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. NLRP3 and ASC are both required for caspase-1 activation through the caspase-11-dependent pathway induced by Legionella pneumophila, caspase-11 is required for NAIP/NLRC4-independent pyroptosis Induced by Legionella pneumophila
physiological function
-
mechanisms and implications of caspase-11-mediated noncanonical inflammasome activation, importance of this pathway in regulating host defense against intracellular bacterial pathogens. The pathway engages caspase-11 to trigger both caspase-1-dependent and -independent production of the inflammatory cytokines IL-1beta, IL-18, and IL-1alpha, as well as to promote pyroptosis, a form of genetically programmed cell death that is associated with the release of such cytokines. Caspase-11 is regulated in response to extracellular stimuli, such as lipopolysaccharide and interferons. Regulation of caspase-11 expression, models of activation, and caspase-11 effector functions, overview. Role of caspase-11 in pyroptosis, caspase-11 directly controls the activation of the effector caspases 3 and 7 of the apoptotic pathway independent of caspase-1
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CASP4_MOUSE
373
0
42742
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
the adaptor protein TRIF upregulates procaspase-11 expression, and this upregulation is required for caspase-11 processing and activation
proteolytic modification
-
TRIF is required for the processing of procaspase-11 into the cleaved caspase-11 forms. IFNs or lipopolyaccharides alone are not sufficient to trigger caspase-11 processing, but an unidentified factor derived from live Gram-negative bacteria is required, which is likely a mechanism to ensure that inflammatory responses do not proceed in the absence of active infection
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D285A
mutation disrupts the processing site in the linker region between the large and small subunits of caspase-11
additional information
additional information
-
targeting Casp11 exon 5 for deletion in C57BL/6 embryonic stem cells. Strain 129 mice, like Casp11-/- mutant mice, exhibits defects in IL-1beta production and harbours a mutation in the Casp11 locus that attenuates caspase-11 expression
additional information
-
all Casp1-/- mice also lack caspase-11, due to the generation of the Casp1-/- line in the 129 mouse strain background, which express a mis-spliced and truncated version of the Casp11 messenger RNA
additional information
-
all Casp1-/- mouse strains generated from 129 embryonic stem cells also lack caspase-11 due to a 5-bp deletion in the caspase-11 locus that causes loss of the catalytic domain. As the caspase-11 and caspase-1 loci are located physically close together, the mutations do not segregate during backcrossing, leading to double mutant mice
additional information
-
generation of Casp11-/- knockout mice, overview. The common mouse knockout strategy is to inject genetically targeted 129-derived ES cells into host C57BL/6 blastocysts and then backcross the chimera with other strains, commonly C57BL/6, for over 10 generations
additional information
-
generation of Casp11-/- mice, all existing caspase-1 deficient mice also lack Caspase-11 due to the backcrossing of a mutant Casp11 allele from 129 into C57BL/6 mice
additional information
-
recombination and segregation of the nonfunctional Casp11 gene away from the Casp1-/- locus is nearly impossible because Casp1 and Casp11 occur only about 1500 bp apart on chromosome 9 in mice
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene CASP11, overexpression of FLAG-tagged enzyme in HEK-293T cells, co-expression with HA-tagged cationic channel subunit transient receptor potential channel 1, i.e. TRPC1, subunits p10 and p20 of caspase-11, but not caspase recruitment domain (CARD) alone, is co-immunoprecipitated with TRPC1. FLAG-tagged caspase-11 is able to co-immunoprecipitate independently with HA-tagged TRPC1 N-terminal alone, the N-terminal domain with the transmembrane domain, and the transmembrane domain with the C-terminal domain, but not with the central transmembrane domain alone
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
bacterial lipopolysaccharide stimulation of caspase-11 expression in several mouse tissues, particularly in the spleen
-
cytosolic infection of cells with Burkholderia species and cytyosolic mutants of Salmonella typhimurium and Legionella pneumophila trigger the enzyme
-
induction of procaspase-11 expression is delayed in Myd88-/- macrophages infected with DELTAFlag Salmonella typhimurium, although procaspase-11 processing itself remains intact
-
Lipopolysaccharide treatment or type I IFN treatment alone does not cause caspase-11-dependent cell death
-
type I IFN signaling is sufficient to induce caspase-11 upregulation and processing. The adaptor protein TRIF upregulates procaspase-11 expression, and this upregulation is required for caspase-11 processing and activation
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
caspase-11 has a regulatory role in ethanol-induced apoptosis. Suppression of caspase-11 may be a mechanism by which Scutellariae radix (Chineses herbal medicine) exerts its cytoprotective effect
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chang, H.Y.; Yang, X.
Proteases from cell suicide: functions and regulation of caspases
Microbiol. Mol. Biol. Rev.
64
821-846
2000
Mus musculus
van de Craen, M.; Vandenabeele, P.; Declercq, W.; van den Brande, I.; van Loo, G.; Molemans, F.; Schotte, P.; van Criekinge, W.; Beyaert, R.; Fiers, W.
Characterization of seven murine caspase family members
FEBS Lett.
403
61-69
1997
Mus musculus (P70343), Mus musculus C3H/An (P70343)
Wang, S.; Miura, M.; Jung, Y.K.; Zhu, H.; Gagliardini, V.; Shi, L.; Greenberg, A.H.; Yuan, J.
Identification and characterization of Ich-3, a member of the interleukin-1beta converting enzyme (ICE)/Ced-3 family and an upstream regulator of ICE
J. Biol. Chem.
271
20580-20587
1996
Mus musculus (P70343), Mus musculus, Mus musculus C57BL/6 X CBA (P70343)
Wang, S.; Miura, M.; Jung, Y.K.; Zhu, H.; Li, E.; Yuan, J.
Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE
Cell
92
501-509
1998
Mus musculus
Kang, S.J.; Wang, S.; Hara, H.; Peterson, E.P.; et al.
Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions
J. Cell Biol.
149
613-622
2000
Mus musculus
Kang, K.; Oh, Y.K.; Choue, R.; Kang, S.J.
Scutellariae radix extracts suppress ethanol-induced caspase-11 expression and cell death in N(2)a cells
Brain Res. Mol. Brain Res.
142
139-145
2005
Mus musculus
Arai, H.; Furuya, T.; Yasuda, T.; Miura, M.; Mizuno, Y.; Mochizuki, H.
Neurotoxic effects of lipopolysaccharide on nigral dopaminergic neurons are mediated by microglial activation, interleukin-1beta, and expression of caspase-11 in mice
J. Biol. Chem.
279
51647-51653
2004
Mus musculus
Endo, M.; Mori, M.; Akira, S.; Gotoh, T.
C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation
J. Immunol.
176
6245-6253
2006
Mus musculus
Furuya, T.; Hayakawa, H.; Yamada, M.; Yoshimi, K.; Hisahara, S.; Miura, M.; Mizuno, Y.; Mochizuki, H.
Caspase-11 mediates inflammatory dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinsons disease
J. Neurosci.
24
1865-1872
2004
Mus musculus
Li, J.; Yin, H.L.; Yuan, J.
Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity
J. Cell Biol.
181
321-333
2008
Mus musculus
Bailly, M.
Moving away from death: when caspase-11 meets cofilin
Nat. Cell Biol.
9
245-246
2007
Mus musculus
Li, J.; Brieher, W.M.; Scimone, M.L.; Kang, S.J.; Zhu, H.; Yin, H.; von Andrian, U.H.; Mitchison, T.; Yuan, J.
Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization
Nat. Cell Biol.
9
276-286
2007
Mus musculus
Namba, T.; Tanaka, K.I.; Ito, Y.; Ishihara, T.; Hoshino, T.; Gotoh, T.; Endo, M.; Sato, K.; Mizushima, T.
Positive Role of CCAAT/Enhancer-Binding Protein Homologous Protein, a Transcription Factor Involved in the Endoplasmic Reticulum Stress Response in the Development of Colitis
Am. J. Pathol.
174
1786-1798
2009
Mus musculus (P70343)
Yi, J.Y.; Hirabayashi, Y.; Choi, Y.K.; Kodama, Y.; Kanno, J.; Han, J.H.; Inoue, T.; Yoon, B.I.
Benzene activates caspase-4 and -12 at the transcription level, without an association with apoptosis, in mouse bone marrow cells lacking the p53 gene
Arch. Toxicol.
83
795-803
2009
Mus musculus
Suyama, K.; Ohmuraya, M.; Hirota, M.; Ozaki, N.; Ida, S.; Endo, M.; Araki, K.; Gotoh, T.; Baba, H.; Yamamura, K.
C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis
Biochem. Biophys. Res. Commun.
367
176-182
2008
Mus musculus (P70343)
Heo, H.; Yoo, L.; Shin, K.S.; Kang, S.J.
Suppression of caspase-11 expression by histone deacetylase inhibitors
Biochem. Biophys. Res. Commun.
378
79-83
2009
Mus musculus
Lee, J.M.; Kim, Y.J.; Ra, H.; Kang, S.J.; Han, S.; Koh, J.Y.; Kim, Y.H.
The involvement of caspase-11 in TPEN-induced apoptosis
FEBS Lett.
582
1871-1876
2008
Mus musculus
Ra, H.; Kim, H.L.; Lee, H.W.; Kim, Y.H.
Essential role of p53 in TPEN-induced neuronal apoptosis
FEBS Lett.
583
1516-1520
2009
Mus musculus
Bulosan, M.; Pauley, K.M.; Yo, K.; Chan, E.K.; Katz, J.; Peck, A.B.; Cha, S.
Inflammatory caspases are critical for enhanced cell death in the target tissue of Sjoegrens syndrome before disease onset
Immunol. Cell Biol.
87
81-90
2009
Mus musculus
Melcher, M.; Unger, B.; Schmidt, U.; Rajantie, I.A.; Alitalo, K.; Ellmeier, W.
Essential roles for the Tec family kinases Tec and Btk in M-CSF receptor signaling pathways that regulate macrophage survival
J. Immunol.
180
8048-8056
2008
Mus musculus
Choi, J.R.; Heo, H.; Lang, Y.; Shin, K.S.; Kang, S.J.
Apoptosis signal-regulating kinase 1 regulates the expression of caspase-11
FEBS Lett.
583
3016-3020
2009
Mus musculus
Kayagaki, N.; Warming, S.; Lamkanfi, M.; Vande Walle, L.; Louie, S.; Dong, J.; Newton, K.; Qu, Y.; Liu, J.; Heldens, S.; Zhang, J.; Lee, W.P.; Roose-Girma, M.; Dixit, V.M.
Non-canonical inflammasome activation targets caspase-11
Nature
479
117-121
2011
Mus musculus, Mus musculus C57BL/6
Shin, S.; Brodsky, I.E.
Caspase-11: the noncanonical guardian of cytosolic sanctity
Cell Host Microbe
13
243-245
2013
Mus musculus
Ng, T.M.; Monack, D.M.
Revisiting caspase-11 function in host defense
Cell Host Microbe
14
9-14
2013
Homo sapiens, Mus musculus
Py, B.F.; Jin, M.; Desai, B.N.; Penumaka, A.; Zhu, H.; Kober, M.; Dietrich, A.; Lipinski, M.M.; Henry, T.; Clapham, D.E.; Yuan, J.
Caspase-11 controls interleukin-1beta release through degradation of TRPC1
Cell Rep.
6
1122-1128
2014
Mus musculus, Mus musculus C57B6
Vigano, E.; Mortellaro, A.
Caspase-11: the driving factor for noncanonical inflammasomes
Eur. J. Immunol.
43
2240-2245
2013
Homo sapiens, Mus musculus
Stowe, I.; Lee, B.; Kayagaki, N.
Caspase-11: arming the guards against bacterial infection
Immunol. Rev.
265
75-84
2015
Mus musculus
Case, C.L.; Kohler, L.J.; Lima, J.B.; Strowig, T.; de Zoete, M.R.; Flavell, R.A.; Zamboni, D.S.; Roy, C.R.
Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila
Proc. Natl. Acad. Sci. USA
110
1851-1856
2013
Mus musculus, Mus musculus C57BL/6
Aachoui, Y.; Leaf, I.A.; Hagar, J.A.; Fontana, M.F.; Campos, C.G.; Zak, D.E.; Tan, M.H.; Cotter, P.A.; Vance, R.E.; Aderem, A.; Miao, E.A.
Caspase-11 protects against bacteria that escape the vacuole
Science
339
975-978
2013
Mus musculus, Mus musculus C57BL/6
Allen, J.; Gyorke, C.E.; Tripathy, M.K.; Zhang, Y.; Lovett, A.; Montgomery, S.A.; Nagarajan, U.M.
Caspase-11 contributes to oviduct pathology during genital Chlamydia infection in mice
Infect. Immun.
87
e00262
2019
Mus musculus (P70343), Mus musculus
Lee, B.L.; Stowe, I.B.; Gupta, A.; Kornfeld, O.S.; Roose-Girma, M.; Anderson, K.; Warming, S.; Zhang, J.; Lee, W.P.; Kayagaki, N.
Caspase-11 auto-proteolysis is crucial for noncanonical inflammasome activation
J. Exp. Med.
215
2279-2288
2018
Mus musculus (P70343), Mus musculus
Sun, Y.; Abbondante, S.; Karmakar, M.; De Jesus Carrion, S.; Che, C.; Hise, A.; Pearlman, E.
Neutrophil caspase-11 is required for cleavage of caspase-1 and secretion of IL-1beta in Aspergillus fumigatus infection
J. Immunol.
201
2767-2775
2018
Mus musculus (P70343)
Kayagaki, N.; Stowe, I.B.; Lee, B.L.; ORourke, K.; Anderson, K.; Warming, S.; Cuellar, T.; Haley, B.; Roose-Girma, M.; Phung, Q.T.; Liu, P.S.; Lill, J.R.; Li, H.; Wu, J.; Kummerfeld, S.; Zhang, J.; Lee, W.P.; Snipas, S.J.; Salvesen, G.S.; Morris, L.X.; Fitzgerald, L.; Zhang, Y.; Bertram, E.M.; Goodnow, C.C.; Di, D.i.x.
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Nature
526
666-671
2015
Mus musculus (P70343), Mus musculus
Flood, B.; Manils, J.; Nulty, C.; Flis, E.; Kenealy, S.; Barber, G.; Fay, J.; Mills, K.H.G.; Kay, E.W.; Creagh, E.M.
Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
Oncogene
38
2658-2674
2019
Mus musculus (P70343), Mus musculus
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