Information on EC 3.4.22.62 - caspase-9

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
3.4.22.62
-
RECOMMENDED NAME
GeneOntology No.
caspase-9
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-Asp-/-Xaa
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
APAF
-
-
-
-
Apaf-3
-
-
-
-
apoptotic protease activating factor 3
-
-
-
-
apoptotic protease Mch-6
-
-
-
-
C14.010
-
-
-
-
CASP-9
-
-
-
-
casp9
-
-
casp9
-
-
casp9
Mus musculus C57BL/6J
-
-
-
casp9-gamma
-
caspase-9 splice variant contains only a caspase recruitment domain and lacks the catalytic domain; caspase-9 splice variant contains only a caspase recruitment domainand lacks the catalytic domain
caspase 9
-
-
-
-
caspase 9
-
-
caspase 9
-
-
caspase-9
-
-
ICE-LAP6
-
-
-
-
ICE-like apoptotic protease 6
-
-
-
-
Mch6
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
180189-96-2
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene CSP9
-
-
Manually annotated by BRENDA team
multiple sclerosis (MS) patients
SwissProt
Manually annotated by BRENDA team
gene Lyccasp9
-
-
Manually annotated by BRENDA team
6-week-old female CD1 mice
SwissProt
Manually annotated by BRENDA team
C57BL, wild type and p53KO mice
-
-
Manually annotated by BRENDA team
Dyrk1A+/- and tgYAC152f7 genotypes
SwissProt
Manually annotated by BRENDA team
murine model for cell therapy-induced type I diabetes
SwissProt
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
neonatal rats
-
-
Manually annotated by BRENDA team
neonatal Wistar rats
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
Wistar
-
-
Manually annotated by BRENDA team
newborn piglet
-
-
Manually annotated by BRENDA team
newborn piglets, aged 2-5 days
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
multiple sequence alignment and phylogenetic tree show that fish and human caspase 9 are highly evolutionarily conserved
evolution
-
members of the caspase family can be subdivided into initiator and effector caspases depending on their placement within the cascade of apoptosis signal transduction. Initiator caspases comprise caspase-2, -8, -9 and -10, which are capable of activating downstream caspases (executioners) after cleavage either directly through proteolysis or indirectly via a secondary messenger mechanism
evolution
-
key structural and catalytic features are conserved across the entire family of cysteine-dependent aspartate-specific proteases (caspases)
malfunction
-
inhibition of caspase-9 activity results in unexpected, marked enhancement of cell death, inhibition of caspase-9 blocks the autophagic process by modulating lysosomal pH and acid-dependent cathepsin activities and augments cell death due to blockage of cytoprotective autophagy. Knockdown of caspase-9 expression by specific siRNA causes increased susceptibility to NSAID FR122047-induced cell death
malfunction
-
loss of caspase-9 results in increased DNA damage and mutation burden after exposure to alkylating agents. Casp9 deficiency results in decreased erythroid and B-cell progenitor abundance and impaired function of hematopoietic stem cells after transplantation. Loss of Casp9 alters hematopoietic progenitor cell frequency
malfunction
-
introduction of a dominant negative Casp9 inhibits mitochondrial remodeling without affecting the release of cytochrome c
malfunction
-
caspase-9 inactivation by specific siRNA restrains the cleavage of Bcl-2 and Bcl-xL, inhibition of caspase-9 also prevents the degradation of Bcl-2 and Bcl-xL
malfunction
-
caspase-9 inhibition induces functional neuroprotection
malfunction
Mus musculus C57BL/6J
-
loss of caspase-9 results in increased DNA damage and mutation burden after exposure to alkylating agents. Casp9 deficiency results in decreased erythroid and B-cell progenitor abundance and impaired function of hematopoietic stem cells after transplantation. Loss of Casp9 alters hematopoietic progenitor cell frequency
-
metabolism
-
p53 mediates DNA damaging drug-induced apoptosis in IMR32 cells through the caspase-9 pathway, molecular pathway, overview
metabolism
-
activation of caspase-9 and caspase-3 via proteolytic cleavage is crucial for the regulation of the apoptotic program
metabolism
-
caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis, which is is a form of programmed cell death that is regulated by the Bcl-2 family and caspase family of proteins. The caspase cascade is responsible for executing cell death following cytochrome c release. Caspase-9 is required for mitochondrial morphological changes and reactive oxygen species production by cleaving and activating Bid into tBid. After activation by caspase-9, caspase-3 inhibits reactive oxygen species production and is required for efficient execution of apoptosis, while effector caspase-7 is required for apoptotic cell detachment
metabolism
-
caspase-9 regulates Puma and caspase-3 activation in apoptosis in cancer cells
physiological function
-
involvement of caspase-9 in autophagy-mediated cell survival pathway
physiological function
-
caspase-9 is initiator in the mitochondrial pathway. Cyt-c and dATP bind in the cytoplasm to an adaptor protein named Apaf-1 and promote formation of the multi-protein apoptosome complex that binds the pro-casp-9. Consequently pro-casp-9 oligomerizes within this complex and is activated by it own autocleavage. In addition to its function as initiator of the mitochondrial apoptotic cascade, caspase-9 can acts also as an executer which among other non-apoptotic functions it forms an Sp1-p53 complex that activates the long terminal repeats by binding to an Sp1 recognition site residing in the long terminal repeats. Ectopic casp-9 but not ectopic casp-3 activates the LTR expression and induces the Sp1-p53 complex formation and its binding to the ERR-1 oligonucleotide
physiological function
-
activation of caspase-9 requires mitochondrial release of cytochrome c to the cytoplasm during apoptosis
physiological function
-
caspase-9 mediates activation of the mitochondrial death pathway, induced by trichothecin and leading to apoptosis of HepG2 cells with diminished expression of antiapoptotic protein Bcl-2 and enhanced expression of proapoptotic protein Bax at mRNA levels, molecular mechanism, overview. The decrement of mitochondrial function results from the overloaded calcium and ROS production
physiological function
-
caspase-9 may play an essential role in Cd induced apoptosis
physiological function
-
caspase-3 activation is induced by caspase-9
physiological function
-
caspase-9 is an upstream or initiator caspase that is regulated differently from all other caspases, as interaction with natural inhibitor XIAP-BIR3 occurs at the dimer interface maintaining caspase-9 in an inactive monomeric state
physiological function
-
caspase-9 is required for normal development of myeloid, lymphoid, and erythroid cells in mice. Role of caspase-9, the initiator caspase of the intrinsic apoptotic cascade, in murine fetal and adult hematopoiesis, overview
physiological function
-
caspase-9 is required for mitochondrial morphological changes and reactive oxygen species production by cleaving and activating Bid into tBid, it activates caspase-3 and is necessary to remodel the mitochondria during intrinsic apoptosis
physiological function
-
caspase-9 induces feedback apoptosis of the mitochondrion by the cleavage of antiapoptotic Bcl-2 and Bcl-xL. Caspase-9 mediates Puma activation in protein kinase inhibitor 7-hydroxystaurosporine UCN-01-induced apoptosis, UCN-01 triggers Puma-induced mitochondrial apoptosis pathway, p53-independent Puma induction is pivotal for the anticancer effects of UCN-01. Caspase-9 enhances Puma activation by cleaving Bcl-2 and Bcl-xL independent of caspase-3. Caspase-9 also directly activates caspase-3 and apoptosis
physiological function
-
caspase-9 is the essential initiator caspase required for apoptosis signalling through the mitochondrial pathway, dynamics of caspase-9 signalling on the apoptosome, detailed overview
physiological function
-
caspase-9 mediates traumatic photoreceptor death, contribution of caspase-9 to photoreceptor death in commotio retinae, overview
physiological function
-
initiator caspases, such as caspase-9, function in recruitment and regulation and are designated as caspase activation and recruitment domains. As an initiator, caspase-9 regulates the upstream stages of the apoptotic caspase cascade, making it a critical control point. Inhibition by zinc has a regulatory function, and its relief is central to both small-molecule and natively induced caspase activation
physiological function
Mus musculus C57BL/6J
-
caspase-9 is required for normal development of myeloid, lymphoid, and erythroid cells in mice. Role of caspase-9, the initiator caspase of the intrinsic apoptotic cascade, in murine fetal and adult hematopoiesis, overview
-
metabolism
-
of the caspases involved in apoptosis signal transduction, the initiator caspases-2, -8 and -9 are activated at multi-protein activation platforms, and activation is thought to involve homo-dimerisation of the monomeric zymogens. Modeling of caspase-9 signalling dynamics on the apoptosome, overview
additional information
-
treatment with the NSAID FR122047 promotes apoptosis and caspase activation in MCF-7 cells
additional information
-
during H2O2-induced apoptosis, caspase 3 is activated directly through caspase 8 and not through the mitochondria-dependent caspase 9 activation
additional information
-
the caspase family signature histidine active-site H236SQYDCCVVIMLSHG250, the cysteine active-site K290PKLFFIQACGG301 and the caspase 9 characteristic pentapeptide active-site QACGG are located in the p20 domain
additional information
-
modeling of the regulation of caspase-9 activation and activity that arise from the complexity of multi-protein interactions at the apoptosome
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ac-LEDH-4-nitroanilide + H2O
Ac-LEDH + 4-nitroaniline
show the reaction diagram
-
-
-
?
acetyl-Asp-Glu-Val-Asp-p-nitroanilide + H2O
acetyl-Asp-Glu-Val-Asp + p-nitroanilide
show the reaction diagram
-
i.e. Ac-DEVD-pNA, caspase-9/-3 activation in differentiated cells can be prevented by protein kinase C (PKC) and the mitogen activated protein kinase (MEK) signaling pathways
-
?
acetyl-DEVD-7-amido-4-methylcoumarin + H2O
acetyl-DEVD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
acetyl-DEVD-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-DEVD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
activation of caspase-3 by caspase-9 indirectly measured by caspase-3 assay
-
?
acetyl-DEVD-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-DEVD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
apoptosome inhibitors analyzed, caspase-9 activity indirectly measured by caspase-3 assay
-
?
acetyl-Ile-Glu-Thr-Asp-p-nitroanilide + H2O
acetyl-Ile-Glu-Thr-Asp + p-nitroaniline
show the reaction diagram
-
13% of the activity with acetyl-Leu-Glu-His-Asp-p-nitroanilide
-
?
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethyl coumarin
show the reaction diagram
-
-
-
?
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethyl coumarin
show the reaction diagram
-
-
-
?
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethyl coumarin
show the reaction diagram
-
activity of caspase-9 determined after treatment of cells with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) for 0.5, 1, 2, 3 and 4 h
-
?
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
?
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
?
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
i.e. Ac-Leu-Glu-His-Asp-MCA, fluorescence assay, 50 microg cell lysate incubated with 5 microl of 1 mM substrate
-
?
acetyl-Leu-Glu-His-Asp-p-nitroanilide + H2O
acetyl-Leu-Glu-His-Asp + p-nitroaniline
show the reaction diagram
-
-
-
?
acetyl-Leu-Glu-His-Asp-p-nitroanilide + H2O
acetyl-Leu-Glu-His-Asp + p-nitroaniline
show the reaction diagram
-
i.e. Ac-LEHD-pNA, caspase-9 activity assay
-
?
acetyl-Leu-Glu-His-Asp-p-nitroanilide + H2O
acetyl-Leu-Glu-His-Asp + p-nitroaniline
show the reaction diagram
-
i.e. Ac-LEHD-pNA, caspase-9/-3 activation in differentiated cells can be prevented by protein kinase C (PKC) and the mitogen activated protein kinase (MEK) signaling pathways
-
?
acetyl-Leu-Glu-His-Asp-p-nitroanilide + H2O
acetyl-Leu-Glu-His-Asp + p-nitroaniline
show the reaction diagram
-
i.e. LEHD-pNA, caspase-9 activity determined, anti-apoptotic cell survival function of cadmium
-
?
acetyl-Trp-Glu-His-Asp-p-nitroanilide + H2O
acetyl-Trp-Glu-His-Asp + p-nitroaniline
show the reaction diagram
-
49% of the activity with acetyl-Leu-Glu-His-Asp-p-nitroanilide
-
?
acetyl-Val-Glu-Ile-Asp-p-nitroanilide + H2O
acetyl-Val-Glu-Ile-Asp + p-nitroaniline
show the reaction diagram
-
19% of the activity with acetyl-Leu-Glu-His-Asp-p-nitroanilide
-
?
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
Bcl-2 + H2O
?
show the reaction diagram
-
-
-
-
?
BclxL + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Leu-Glu-His-Asp-7-amido-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Leu-Glu-His-Asp-7-amino-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
?
inactive Bid + H2O
active tBid + ?
show the reaction diagram
-
cleavage at amino acid 59, cleavage at amino acid 59. Substrate mutants BidD98A and BidD75A are cleaved by caspase-9, mutant BidD59A is not cleaved
-
?
inactive procaspase-7 variant C186A + H2O
active caspase-7 variant C186A + ?
show the reaction diagram
-
-
-
?
L-histidine decarboxylase precursor + H2O
?
show the reaction diagram
-
in P-815 cells, histamine synthesis is augmented through the post-translational cleavage of L-histidine decarboxylase, which is mediated by caspase-9
-
-
?
L-histidine decarboxylase precursor + H2O
?
show the reaction diagram
Mus musculus BDF1
-
in P-815 cells, histamine synthesis is augmented through the post-translational cleavage of L-histidine decarboxylase, which is mediated by caspase-9
-
-
?
LEDH-4-nitroanilide + H2O
LEDH + 4-nitroaniline
show the reaction diagram
-
-
-
?
LEHD-7-amido-4-methylcoumarin + H2O
LEHD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
N-acetyl-LEHD-4-trifluoromethylcoumarin 7-amide + H2O
N-acetyl-LEHD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
?
N-acetyl-Leu-Glu-His-Asp-7-amido-4-fluorocoumarin + H2O
N-acetyl-Leu-Glu-His-Asp + 7-amino-4-fluorocoumarin
show the reaction diagram
-
-
-
?
poly (ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
i.e. PARP
-
-
?
poly(ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
-
-
?
pro-caspase-2L + H2O
caspase-2L + ?
show the reaction diagram
mechanisms of apoptotic pathways controlling fragmentation of unfertilized ovulated oocyte, caspase-3 and caspase-2L (long isoform) transcripts and proteins present in oocytes during ealy stages of meiosis, zymogen and cleaved forms, mechanisms of apoptotic pathways controlling fragmentation of unfertilized ovulated oocyte, caspase-9, caspase-3 and caspase-2L (long isoform) transcripts and proteins present in oocytes during ealy stages of meiosis, zymogen and cleaved forms
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
caspase-9/-3 activation in differentiated cells can be prevented by protein kinase C (PKC) and the mitogen activated protein kinase (MEK) signaling pathways
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
high linear energy transfer (LET) radiation enhances apoptosis by activation of caspase-3 through caspase-9
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
induction of oxidative cell death by marine sponge extracts of Polymastia janeirensis mediated through caspase-9 apoptotic pathway
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
mechanisms of adenosine-induced apoptosis in human colonic cancer cells
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
mechanisms of apoptosis induced by ionizing radiation on cell lines with a different status of p53 (TP53 tumor suppressor gene), extrinsic (caspase-8 dependent) and intrinsic (caspase-9 dependent) pathways activated
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
mechanisms of apoptotic pathways controlling fragmentation of unfertilized ovulated oocyte, caspase-9, caspase-3 and caspase-2L (long isoform) transcripts and proteins present in oocytes during ealy stages of meiosis, zymogen and cleaved forms
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
mechanisms of cordycepin-induced apoptosis, activation of caspase-9, caspase-3 and caspase-7
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
requirement of caspase-3 for cell differentiation, activation of caspase-3 by caspase-9 promotes differentiation of skeletal myoblasts into myotubes
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
signalling pathways of CD20-induced apoptosis analyzed by using the chimeric mouse-human anti-CD20 antibody rituximab, activation of caspase-9 essential for rituximab-mediated apoptosis, mitochondrial role in rituximab-induced apoptosis, overexpression of caspase-9 inhibits the rituximab-induced activation of caspase-3
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
activation of caspase-3 by caspase-9 indirectly measured by caspase-3 assay
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
apoptosome inhibitors analyzed, caspase-9 activity indirectly measured by caspase-3 assay
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
gradual increase in caspase-3 activities in cells treated with recombinant Vibrio vulnificus cytolysin (rVVC) during 0.5-3 h incubation and a slight decrease after incubation for 4 h
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
activated caspase-9 cleaves and activates caspase-3
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
increased activity of caspase-9 to 407% and of caspase-3 to 540% after cell treatment with atorvastatin
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
Rattus norvegicus Wistar
-
increased activity of caspase-9 to 407% and of caspase-3 to 540% after cell treatment with atorvastatin
-
-
?
pro-caspase-3 + H2O
caspase-3
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
?
pro-caspase-3 + H2O
active caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
?
pro-caspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
pro-caspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
mechanisms of cordycepin-induced apoptosis, activation of caspase-9, caspase-3 and caspase-7
-
?
pro-caspase-9 + H2O
caspase-9
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
?
pro-caspase-9 + H2O
caspase-9 + ?
show the reaction diagram
-
auto-processing, apoptosis induced by tumor necrosis factor (TNF)-alpha promotes dephosphorylation of caspase-9 by casein kinase 2 (CK2), phosphorylation by casein kinase 2 decreases susceptibility of caspase-9 to cleavage by active caspase-8
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
retinoblastoma protein Rb + H2O
p76Rb + ?
show the reaction diagram
-
caspase-9 interferes, upstream of the mitochondrion, with P53-induced apoptosis in both immortalized and primary fibroblasts. The involvement of caspase-9 in a premitochondrial protective pathway results from the cleavage of retinoblastoma protein Rb (tumor suppressor), at a LExD site, into a p76Rb form, which antagonizes p53-induced apoptosis
-
?
LEHD-7-amido-4-methylcoumarin + H2O
LEHD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
additional information
?
-
-
LEHD is the optimal tetrapeptide recognition motif
-
-
-
additional information
?
-
-
the preferred cleavage sequence is LEHD-/-
-
-
-
additional information
?
-
-
a peroxisome proliferator-activated receptor-gamma agonist, troglitazone, facilitates caspase-8 and -9 activities by increasing the enzymatic activity of protein-tyrosine phosphatase-1B on human glioma cells
-
-
-
additional information
?
-
-
activated caspase-9 prevents the accessibility of cytochrome c to complex III, resulting in the production of reactive oxygen species, and that effector caspases may depolarize mitochondria to terminate ROS production and preserve an apoptotic phenotype
-
-
-
additional information
?
-
-
activation of caspase-9 is a key step for execution of the maternally preset program of apoptosis shortly after midblastula transition in Xenopus early embryos
-
-
-
additional information
?
-
-
although Apaf-1 and caspase-9 are essential for mast cell apoptosis, neither is required for the functional or clonogenic death of the cells, which may be due to mitochondrial dysfunction
-
-
-
additional information
?
-
-
caspase-2, -3, -8 and -9 are expressed and active in the rhesus monkey corpus luteum throughout the luteal phase of the natural menstrual cycle. The primary luteotropic hormone of corpus luteum can enhance the activity of effector caspases (-2, -8, and -9) after 3-day exposure
-
-
-
additional information
?
-
-
caspase-9 is dispensable for activation of cyclin-dependent kinase 5 during cell death
-
-
-
additional information
?
-
-
caspase-9 is involved in endoplasmic reticulum stress-induced apoptosis
-
-
-
additional information
?
-
-
caspase-9 plays a crucial role in the initiation of the initiation phase of the intrinsic apoptosis pathway. Caspase-9 gene mutation may not contribute to the pathogenesis of human cancer (gastric, colorectal and lung carcinomas)
-
-
-
additional information
?
-
-
caspase-9 plays a marginal role in serum starvation-induced apoptosis. Caspase-9 sequestration represents a cellular mechanism to impair apoptosome assembly
-
-
-
additional information
?
-
-
detection of both caspase-8 and caspase-9 activity in oocytes shows that unfertilized oocytes have the machinery to undergo apoptosis by using either the extrinsic (caspase-8 dependent) or intrinsic (caspase-9 dependent) pathways
-
-
-
additional information
?
-
-
differential caspase-9-dependent signaling pathway between tumor necrosis factor receptor- and Fas-mediated hepatocyte apoptosis
-
-
-
additional information
?
-
-
local apoptosis of lymphatic tissue in polymicrobial sepsis is processed dependent on caspase-9
-
-
-
additional information
?
-
-
NO generated during hypoxia leads to activation of caspase-9 and results in initiation of caspase-cascade-dependent hypoxic neuronal death
-
-
-
additional information
?
-
-
caspase-2, -3, -8 and -9 are expressed and active in the rhesus monkey corpus luteum throughout the luteal phase of the natural menstrual cycle. The primary luteotropic hormone of corpus luteum, can enhance the activity of effector caspases (-2, -8, and -9) after 3-day exposure
-
-
-
additional information
?
-
-
caspase-9 plays a marginal role in serum starcvation-induced apoptosis. caspase-9 sequestration represents a cellular mechanism to impair apoptosome assembly
-
-
-
additional information
?
-
-
caspase-8-cleaved caspase-9 induces lysosomal membrane permeabilization but fails to activate the effector caspases whereas apoptosome-dependent activation of caspase-9 can trigger both events. Caspase-9 plays a dual role in cell death signaling, as an activator of effector caspases and lysosomal membrane permeabilization
-
-
-
additional information
?
-
-
caspase-9 is possibly involved in the apoptotic cell death in batch and fed-batch cultures of CHO cells
-
-
-
additional information
?
-
-
caspase-9 signaling cascade induces feedback disruption of the mitochondrion during apoptosis through cleavage of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1
-
-
-
additional information
?
-
-
endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species
-
-
-
additional information
?
-
-
no activity with acetyl-Asp-Glu-Val-Asp-p-nitroanilide and acetyl-Val-Asp-Val-Ala-Asp-p-nitroanilide
-
-
-
additional information
?
-
-
acetylserotonin-O-methyltransferase-like protein identified as a candidate substrate of caspase-9, cytoskeletal proteins associated with un-processed caspase-9 are potential candidates for structural stabilization or as caspase substrates during apoptosis
-
-
-
additional information
?
-
-
effect of fluoride treatment (NaF) on osteoblast proliferation, apoptosis and expression of caspase-9 mRNA in vitro
-
-
-
additional information
?
-
-
knockdown of the cellular-FLICE inhibitory protein (c-FLIP) using small interfering RNA (siRNA) triggers ligand-independent caspase-9-dependent spontaneous apoptosis
-
-
-
additional information
?
-
-
mechanisms of caspase-9 activation mediated by reactive oxygen species (ROS), caspase-9 activation facilitated by cellular oxidative state
-
-
-
additional information
?
-
-
mitochondria-dependent caspase activation for mediation of isorhamnetin-induced apoptosis
-
-
-
additional information
?
-
phosphorylation of caspase-9 at Thr125 by the protein kinase DYRK1A inhibits its cleavage and activation
-
-
-
additional information
?
-
-
threshold for the activation of caspase-9 through basal inhibitory phosphorylation at Thr125, catalyzed by the protein kinase DYRK1A
-
-
-
additional information
?
-
-
apoptosome formation and caspase-9 activation under oxidative stress, oxidative modification of caspase-9 mediates interaction with APAF-1 and promotes its auto-cleavage and activation
-
-
-
additional information
?
-
-
ligand-independent caspase-9-dependent spontaneous apoptosis triggered by knockdown of the cellular-FLICE inhibitory protein (c-FLIP) using small interfering RNA (siRNA)
-
-
-
additional information
?
-
-
caspase-9 cleaves the the LEHD sequence
-
-
-
additional information
?
-
-
catalytic Cys299 residue with a His249 involved in catalysis
-
-
-
additional information
?
-
-
the linker between the large and small subunits contains the caspase-9 auto-cleavage site (D315). Cleavage at this site generates the p35/p12 form of caspase-9. The p35/p12 form can be further processed by caspase-3 by cleavage at site D330, generating caspase-9
-
-
-
additional information
?
-
-
as a cleaved dimer, the L2 loop from one half of the dimer is able to interact with the L2' loop from the other half in the presence of substrate, similarly to other caspases. In this state, the protein is catalytically competent to process substrate. Like other caspases, caspase-9 recognizes its substrates and cleaves after specific aspartic acid residues
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Bcl-2 + H2O
?
show the reaction diagram
-
-
-
-
?
BclxL + H2O
?
show the reaction diagram
-
-
-
-
?
inactive Bid + H2O
active tBid + ?
show the reaction diagram
-
cleavage at amino acid 59
-
?
inactive procaspase-7 variant C186A + H2O
active caspase-7 variant C186A + ?
show the reaction diagram
-
-
-
?
poly (ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
i.e. PARP
-
-
?
pro-caspase-2L + H2O
caspase-2L + ?
show the reaction diagram
Q9R0T0
mechanisms of apoptotic pathways controlling fragmentation of unfertilized ovulated oocyte, caspase-3 and caspase-2L (long isoform) transcripts and proteins present in oocytes during ealy stages of meiosis, zymogen and cleaved forms
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
caspase-9/-3 activation in differentiated cells can be prevented by protein kinase C (PKC) and the mitogen activated protein kinase (MEK) signaling pathways
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
high linear energy transfer (LET) radiation enhances apoptosis by activation of caspase-3 through caspase-9
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
induction of oxidative cell death by marine sponge extracts of Polymastia janeirensis mediated through caspase-9 apoptotic pathway
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
mechanisms of adenosine-induced apoptosis in human colonic cancer cells
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
mechanisms of apoptosis induced by ionizing radiation on cell lines with a different status of p53 (TP53 tumor suppressor gene), extrinsic (caspase-8 dependent) and intrinsic (caspase-9 dependent) pathways activated
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
Q9R0T0
mechanisms of apoptotic pathways controlling fragmentation of unfertilized ovulated oocyte, caspase-9, caspase-3 and caspase-2L (long isoform) transcripts and proteins present in oocytes during ealy stages of meiosis, zymogen and cleaved forms
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
mechanisms of cordycepin-induced apoptosis, activation of caspase-9, caspase-3 and caspase-7
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
requirement of caspase-3 for cell differentiation, activation of caspase-3 by caspase-9 promotes differentiation of skeletal myoblasts into myotubes
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
signalling pathways of CD20-induced apoptosis analyzed by using the chimeric mouse-human anti-CD20 antibody rituximab, activation of caspase-9 essential for rituximab-mediated apoptosis, mitochondrial role in rituximab-induced apoptosis, overexpression of caspase-9 inhibits the rituximab-induced activation of caspase-3
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
activated caspase-9 cleaves and activates caspase-3
-
-
?
pro-caspase-3 + H2O
caspase-3
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
?
pro-caspase-3 + H2O
active caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
pro-caspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
mechanisms of cordycepin-induced apoptosis, activation of caspase-9, caspase-3 and caspase-7
-
?
pro-caspase-9 + H2O
caspase-9
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
?
pro-caspase-9 + H2O
caspase-9 + ?
show the reaction diagram
-
auto-processing, apoptosis induced by tumor necrosis factor (TNF)-alpha promotes dephosphorylation of caspase-9 by casein kinase 2 (CK2), phosphorylation by casein kinase 2 decreases susceptibility of caspase-9 to cleavage by active caspase-8
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
retinoblastoma protein Rb + H2O
p76Rb + ?
show the reaction diagram
-
caspase-9 interferes, upstream of the mitochondrion, with P53-induced apoptosis in both immortalized and primary fibroblasts. The involvement of caspase-9 in a premitochondrial protective pathway results from the cleavage of retinoblastoma protein Rb (tumor suppressor), at a LExD site, into a p76Rb form, which antagonizes p53-induced apoptosis
-
?
L-histidine decarboxylase precursor + H2O
?
show the reaction diagram
Mus musculus, Mus musculus BDF1
-
in P-815 cells, histamine synthesis is augmented through the post-translational cleavage of L-histidine decarboxylase, which is mediated by caspase-9
-
-
?
additional information
?
-
-
a peroxisome proliferator-activated receptor-gamma agonist, troglitazone, facilitates caspase-8 and -9 activities by increasing the enzymatic activity of protein-tyrosine phosphatase-1B on human glioma cells
-
-
-
additional information
?
-
-
activated caspase-9 prevents the accessibility of cytochrome c to complex III, resulting in the production of reactive oxygen species, and that effector caspases may depolarize mitochondria to terminate ROS production and preserve an apoptotic phenotype
-
-
-
additional information
?
-
-
activation of caspase-9 is a key step for execution of the maternally preset program of apoptosis shortly after midblastula transition in Xenopus early embryos
-
-
-
additional information
?
-
-
although Apaf-1 and caspase-9 are essential for mast cell apoptosis, neither is required for the functional or clonogenic death of the cells, which may be due to mitochondrial dysfunction
-
-
-
additional information
?
-
-
caspase-2, -3, -8 and -9 are expressed and active in the rhesus monkey corpus luteum throughout the luteal phase of the natural menstrual cycle. The primary luteotropic hormone of corpus luteum can enhance the activity of effector caspases (-2, -8, and -9) after 3-day exposure
-
-
-
additional information
?
-
-
caspase-9 is dispensable for activation of cyclin-dependent kinase 5 during cell death
-
-
-
additional information
?
-
-
caspase-9 is involved in endoplasmic reticulum stress-induced apoptosis
-
-
-
additional information
?
-
-
caspase-9 plays a crucial role in the initiation of the initiation phase of the intrinsic apoptosis pathway. Caspase-9 gene mutation may not contribute to the pathogenesis of human cancer (gastric, colorectal and lung carcinomas)
-
-
-
additional information
?
-
-
caspase-9 plays a marginal role in serum starvation-induced apoptosis. Caspase-9 sequestration represents a cellular mechanism to impair apoptosome assembly
-
-
-
additional information
?
-
-
detection of both caspase-8 and caspase-9 activity in oocytes shows that unfertilized oocytes have the machinery to undergo apoptosis by using either the extrinsic (caspase-8 dependent) or intrinsic (caspase-9 dependent) pathways
-
-
-
additional information
?
-
-
differential caspase-9-dependent signaling pathway between tumor necrosis factor receptor- and Fas-mediated hepatocyte apoptosis
-
-
-
additional information
?
-
-
local apoptosis of lymphatic tissue in polymicrobial sepsis is processed dependent on caspase-9
-
-
-
additional information
?
-
-
NO generated during hypoxia leads to activation of caspase-9 and results in initiation of caspase-cascade-dependent hypoxic neuronal death
-
-
-
additional information
?
-
-
caspase-2, -3, -8 and -9 are expressed and active in the rhesus monkey corpus luteum throughout the luteal phase of the natural menstrual cycle. The primary luteotropic hormone of corpus luteum, can enhance the activity of effector caspases (-2, -8, and -9) after 3-day exposure
-
-
-
additional information
?
-
-
caspase-9 plays a marginal role in serum starcvation-induced apoptosis. caspase-9 sequestration represents a cellular mechanism to impair apoptosome assembly
-
-
-
additional information
?
-
-
caspase-8-cleaved caspase-9 induces lysosomal membrane permeabilization but fails to activate the effector caspases whereas apoptosome-dependent activation of caspase-9 can trigger both events. Caspase-9 plays a dual role in cell death signaling, as an activator of effector caspases and lysosomal membrane permeabilization
-
-
-
additional information
?
-
-
caspase-9 is possibly involved in the apoptotic cell death in batch and fed-batch cultures of CHO cells
-
-
-
additional information
?
-
-
caspase-9 signaling cascade induces feedback disruption of the mitochondrion during apoptosis through cleavage of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1
-
-
-
additional information
?
-
-
endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species
-
-
-
additional information
?
-
-
acetylserotonin-O-methyltransferase-like protein identified as a candidate substrate of caspase-9, cytoskeletal proteins associated with un-processed caspase-9 are potential candidates for structural stabilization or as caspase substrates during apoptosis
-
-
-
additional information
?
-
-
effect of fluoride treatment (NaF) on osteoblast proliferation, apoptosis and expression of caspase-9 mRNA in vitro
-
-
-
additional information
?
-
-
knockdown of the cellular-FLICE inhibitory protein (c-FLIP) using small interfering RNA (siRNA) triggers ligand-independent caspase-9-dependent spontaneous apoptosis
-
-
-
additional information
?
-
-
mechanisms of caspase-9 activation mediated by reactive oxygen species (ROS), caspase-9 activation facilitated by cellular oxidative state
-
-
-
additional information
?
-
-
mitochondria-dependent caspase activation for mediation of isorhamnetin-induced apoptosis
-
-
-
additional information
?
-
Q9R0T0
phosphorylation of caspase-9 at Thr125 by the protein kinase DYRK1A inhibits its cleavage and activation
-
-
-
additional information
?
-
-
threshold for the activation of caspase-9 through basal inhibitory phosphorylation at Thr125, catalyzed by the protein kinase DYRK1A
-
-
-
additional information
?
-
-
the linker between the large and small subunits contains the caspase-9 auto-cleavage site (D315). Cleavage at this site generates the p35/p12 form of caspase-9. The p35/p12 form can be further processed by caspase-3 by cleavage at site D330, generating caspase-9
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cd2+
-
induces activation of caspase-9, decreases expression of the inactive form pro-caspase-9
Cd2+
-
anti-apoptotic cell survival function of cadmium, cadmium inhibits apoptosis induced by benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) at non-cytotoxic concentrations, cadmium chloride pre-treatment of cells significantly inhibits caspase-9 activation in a dose dependent manner, 40% and 52% inhibition at 10 and 20 microM cadmium chloride, respectively
Cd2+
-
slight activation
Co2+
-
slight activation
NaF
-
NaF-induced apoptosis of osteoblasts
Pb2+
-
slight activation
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3S,6S,10aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide
-
-
(3S,6S,8aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydroindolizine-3-carboxamide
-
-
(3S,6S,9aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide
-
-
acetyl-AEVD-CHO
-
-
acetyl-DEVD-CHO
-
-
acetyl-DVAD fluoromethyl ketone
-
prediction of the tertiary structure of a caspase-9/inhibitor complex
acetyl-IETD-CHO
-
-
acetyl-WEHD-CHO
-
-
acetyl-YVAD-CHO
-
-
ATP
-
enzyme activity is inhibited in both normoxic and hypoxic groups. The IC50 increases 5fold following hypoxia, suggesting a hypoxia-induced modificationof the ATP binding site. 70% inhibition by 1 mM
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-LEHD-fluoromethylketone
-
-
benzyloxycarbonyl-LEHD-fluoromethylketone
-
cell transfection with siRNA against the cellular-FLICE inhibitory protein (c-FLIP) followed by the addition of the caspase-9 inhibitor benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone protects the cells from spontaneous apoptosis, indicates that c-FLIP siRNA-triggered apoptosis occurrs by a caspase-9-dependent process, inhibitor concentration of 20 microM for 48 h, apoptosis determined by counting fragmented nuclei using fluorescent dyes, caspase-9 activation shown by Western blot
benzyloxycarbonyl-LEHD-fluoromethylketone
-
i.e. z-LEHD-FMK, specific caspase-9 inhibitor, concentration of 50 microM, inhibitor effect on isorhamnetin-induced apoptosis, cells exposed to DMSO or 40 microM isorhamnetin for 48 h
benzyloxycarbonyl-LEHD-fluoromethylketone
-
i.e. z-LEHD-FMK, inhibitor effect on apoptosis induced by high linear energy transfer (LET) radiation, induction of apoptosis investigated at 48 h after 10 day irradiation in the presence of 2-100 microM inhibitor concentration, caspase-9 inhibitor suppresses caspase-3 activation and apoptosis induction by radiation to a greater extent than caspase-8 inhibitor
benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone
-
i.e. z-LEHD-FMK, inhibitor concentration 100 microM
benzyloxycarbonyl-VAD-fluoromethylketone
-
t1/2 at 0.001 mM is 3.9 s
benzyloxycarbonyl-VAD-fluoromethylketone
-
-
benzyloxycarbonyl-VAD-fluoromethylketone
i.e. Z-VAD-FMK, in vitro oocyte meiosis and fragmentation analyzed by treatment with concentrations of 50 and 100 microM, transition from metaphase I to metaphase II accelerated in oocytes, comparative treatment with the apoptotic inducer doxorubicin (DXR)
benzyloxycarbonyl-VAE-fluoromethylketone
-
-
benzyloxycarbonyl-Val-Asp-Val-Ala-Asp-fluoromethylketone
-
-
biotin-Val-Ala-Asp-fluoromethyl ketone
-
i.e. biotin-VAD-fmk, presence or absence of 50 microM inhibitor, caspase-9 activation analyzed by affinity labelling and immunoblotting
cadmium
-
anti-apoptotic cell survival function of cadmium, cadmium inhibits apoptosis induced by benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) at non-cytotoxic concentrations, 40% and 52% inhibition at 10 and 20 microM cadmium chloride, respectively
caspase-9S
-
transfection of renal epithelial cells with the dominant-negative inhibitor caspase-9S
-
cowpox serpin CrmA
-
the Ki-value is below 2.3 nM
-
cytochrome c
-
enzyme activity is inhibited in both normoxic and hypoxic groups. The IC50 increases 1.5fold following hypoxia, suggesting a hypoxia-induced modificationof the cytochrome binding site. 70% inhibition by 0.003 mM
L-alanyl-L-valyl-L-prolyl-L-isoleucinamide
-
-
N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-N-[2-(2-fluorophenyl)ethyl]-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 51% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-N-[2-(2-methoxyphenyl)ethyl]-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 1% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-N-[2-(4-fluorophenyl)ethyl]-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72, 34% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-N-(2-cyclopropylethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 16% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-N-butyl-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h for caspase activity assay, 45% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-N-[2-(4-chlorophenyl)ethyl]-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 2% inhibition of caspase-3 activity in SAOS-2 cells
N-benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone
-
i.e. Z-VAD-FMK, treatment with 100 microM caspase inhibitor in combination with 100 microM cordycepin for 24 h suppresses sub-G1 phase in MA-10 cells
N-Fmoc-S-2-(2'-octyl)alanine
-
-
-
N-Fmoc-S-2-(2'-pentyl)alanine
-
-
-
N-[2-(acetylamino)ethyl]-N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 22% inhibition of caspase-3 activity in SAOS-2 cells
NO32-
-
slight inhibition
-
Pen-1-XBIR3
-
caspase-9 is inhibited by unilateral intravitreal injection of highly specific X-linked inhibitor of apoptosis (IAP) baculoviral IAP repeat 3 (XBIR3) domain linked to the cell transduction peptide penetratin 1 (Pen-1) after ballistic injury
-
PGA-1
-
PGA-peptoid conjugate, inhibitor of apoptotic protease activating factor 1 (Apaf-1) coupled to poly-L-glutamic acid (PGA), at concentrations of 50 and 100 microM inhibition of caspase-3 activity, reaches values up to 100% at 50 microM drug after 48 h in HeLa-cells and and after 72 h in SAOS-2 cells
PGA-1
-
PGA-peptoid 1, inhibitor (peptoid 1) of apoptotic protease activating factor 1 (Apaf-1) coupled to poly-L-glutamic acid (PGA)
Q-VD-OPH
-
i.e. (3S)-5-(2,6-difluorophenoxy)-3-[[(2S)-2-(isoquinoline-3-carbonylamino)-3-methylbutanoyl]amino]-4-oxopentanoic acid, cell treatment with the broad-spectrum caspase inhibitor Q-VD-OPH (concentration 30 microM) prior to induction of differentiation
RQIKIWFQNRRMKWKKGG-N-[2-(2,4-dichlorophenyl)ethyl]glycyl-N-(3,3-diphenylpropyl)glycyl-N2-[2-(2,4-dichlorophenyl)ethyl]glycinamide
-
i.e. PEN-1, modified compound with peptide bridge, 5 microM for cell treatment, shows low inhibitory activity of caspase-3
XIAP
-
can antagonise caspase-9 activity and stabilises its interaction with the apoptosome. Caspase-3 cleaves XIAP into fragments that retain their inhibitory potential towards caspases-3 or -9, thereby eliminating sterical hindrance that may prevent parallel inhibition of caspases-3 and -9 by XIAP
-
XIAP-BIR3
-
a natural caspase-9 inhibitor that binds at the dimer interface keeping the enzyme in an inactive monomeric state, binding to the enzyme involves the alpha5 helix of XIAP-BIR3
-
Z-IETD-fluoromethylketone
-
a caspase-8 specific inhibitor, delays the activation of caspase-3 and caspase-9 significantly
Z-LEHD-fluoromethylketone
-
a caspase-9 inhibitor
Z-LEHD-fluoromethylketone
-
a caspase-9 specific inhibitor, inhibits caspase-9 activation completely
Z-VAD-fluoromethylketone
-
a pan-caspase inhibitor
Zn2+
-
mixed-tpe inhibition, kinetics and mechanism of zinc-mediated inhibition of caspase-9, overview. Two distinct zinc-binding sites on caspase-9, the first site, composed of H237, C239, and C287, includes the active site dyad and is primarily responsible for zinc-mediated inhibition. The second binding site at C272 is distal from the active site. EDTA can hinder enzyme inhibition by Zn2+. Zinc-mediated inhibition does not influence the overall structure of caspase-9 monomers. Each wild-type caspase-9 monomer binds two zinc ions. Caspase-9 variants in which the active-site residues are replaced, C287A or H237A, bind just one zinc
Mn2+
-
slight inhibition
additional information
-
inhibition of caspase-9 enhances the viability of the CHO cells in both batch and fed-batch suspension cultures
-
additional information
-
rituximab-induced apoptosis involved in the activation of caspase-9 can be blocked by Bcl-xL overexpression
-
additional information
-
activation of caspase-9 by Cd2+ is inhibited by treatment with the herbal drug Hwanggunchungyitang (HGCYT) in a dose-dependent manner, pretreatement of cells with 0.01-1 mg/ml inhibitor for 1 h, treatment with 10 microM Cd2+ for 24 h
-
additional information
the protein kinase DYRK1A is a negative regulator of the intrinsic apoptotic pathway in the developing retina by phosphorylating caspase-9 on the inhibitory threonine residue 125 to prevent activation
-
additional information
-
DYRK1A-dependent phosphorylation of Thr125 blocked by the kinase inhibitor harmine
-
additional information
-
caspase-9/-3 activation in differentiated cells, inhibited by protein kinase C (PKC) and the mitogen activated protein kinase (MEK) signaling pathways
-
additional information
-
atorvastatin-mediated apoptosis of hepatic stellate cells (HSCs) can be bocked by co-treatment with mevalonic acid and U0126, an activator of the extracellular signal-regulated protein kinase (ERK1/2)
-
additional information
-
development, design and synthesis, of three types of stabilized peptides derived from the alpha5 helix of inhibitor XIAP-BIR3, using incorporation of amino-isobutyric acid, the avian pancreatic polypeptide-scaffold or aliphatic staples, overview. The stabilized peptides are helical in solution and achieve good inhibition, indicating that this allosteric site at the caspase-9 dimerization interface is regulatable with low-molecular weight synthetic ligands and is thus a druggable site. Other caspases, which are not regulated by dimerization, are not inactivated by these peptides
-
additional information
-
caspase-3 can bind to the nucleotide binding domain of Apaf-1 on the apoptosome backbone. Binding eliminates the close association of caspase-9 with the nucleotide binding domain of Apaf-1, resulting in its inactivation
-
additional information
-
no inhibition by Co2+, PB2+, and Cd2+
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-(prop-2-en-1-yl)hydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-(prop-2-yn-1-yl)hydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-benzylhydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-methylhydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]hydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
adenosine
-
extracellular adenosine induces apoptosis by activating caspase-9 and caspase-3 in association with mitochondrial damage via A2a adenosine receptors, induction dose-dependent (1-20 mM) and time-dependent (24-72 h)
APAF-1
-
proteolytic activity of caspase-9 in a complex with APAF-1 is several orders of magnitude higher than that of the free enzyme. Thus, this complex functions as a holoenzyme in which caspase-9 is the catalytic subunit and APAF-1 its allosteric regulator
-
APAF-1
-
caspase-9, Bcl-Xl and Apaf-1 form a ternary complex. Caspase-9 likely represents a direct downstream target of Agaf-1 and its activation appears critical for the propagation of death signals
-
APAF-1
-
caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation
-
APAF-1
-
interaction with APAF-1 promotes auto-cleavage and activation of caspase-9
-
apoptosome
-
activates caspase-9 by dimerization
-
NO
-
NO generated during hypoxia leads to activation of caspase-9 and results in initiation of caspase-cascade-dependent hypoxic neuronal death
staurosporine
-
initiates apoptosis, 25% of the cells are apoptotic in staurosporine-treated cultures, 1 microM for 4 h, used as a positive control for caspase-9 activation in C2C12 cells, mitochondrial changes in apoptotic but not in differentiating cells
cordycepin
-
i.e. 3'-deoxyadenosine, cells treated with 100 mM and 1 mM for 24 h, expression of caspase-9, Western blot analysis
additional information
-
activation of caspase-9 1 h after treatment with a combination of 8-methoxypsoralen and ultraviolet-A radiation
-
additional information
-
benzene, tendency to increase caspase-9 expression after 12 days of oral benzene treatment to p53KO mice
-
additional information
-
atorvastatin induces apoptosis in vitro, dose dependent effect, first detectable after 20 h, increased activity of caspase-9 to 407% and of caspase-3 to 540% after treatment with atorvastatin and/or mevalonic acid (125 microM), with and without the kinase-activator U0126 (10 microM)
-
additional information
-
treatment of HL-60 cells with 1 microM benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) elicits induction of caspase-9 activity
-
additional information
-
treatment with the NSAID FR122047 promotes apoptosis and caspase activation in MCF-7 cells
-
additional information
-
activation dynamics of caspase 9
-
additional information
-
activation of caspase-9 requires mitochondrial release of cytochrome c to the cytoplasm during apoptosis
-
additional information
-
activation of caspase-9 via proteolytic cleavage. Design and synthesis of azapeptide activators of apoptosis mediated by caspase-9 in cancer cells, a set of azapeptides was designed based on the Ala-Val-Pro-Ile peptide (derived from second mitochondria-derived activator of caspase, Smac, protein) to activate caspase-9 and induce apoptosis in breast cancer cells. overview
-
additional information
-
the zymogen caspase-9 has very low activity as a monomer. Activity increases upon dimerization and increases even more profoundly upon interaction with the apoptosome, a heptameric complex formed from association of Apaf-1 and cytochrome c in an ATP-dependent process. Caspase-9 does not require intersubunit cleavage for activation
-
additional information
-
caspase-9 is activated on the apoptosome complex. Through its higher affinity, procaspase-9 displaces processed caspase-9 from the apoptosome, thereby closing the proteolytic timer cycle. Dimerisation of caspase-9 results in rapid autocatalytic cleavage, yielding caspase-9 (p35/p12)
-
additional information
-
the uncleaved monomeric zymogen of caspase-9 has very low activity, which is increased upon dimerization. In dimeric caspase-9 cleavage at a specific aspartate residue in the intersubuint linker between the large and small subunits is required for caspase-9 to attain increased activity. Full enzymatic activity is achieved only upon interaction with the apoptosome, a multicomponent, heptameric caspase-9 activating platform
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.466
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin
-
leucine-zipper-linked dimeric caspase-9
0.686
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin
-
caspase-9 holoenzyme
0.466
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin
-
leucine-zipper-linked dimeric caspase-9
0.686
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin
-
caspase-9 holoenzyme
0.408
acetyl-VEHD-7-amido-4-methylcoumarin
-
pH 6.5
0.78
acetyl-VEHD-7-amido-4-methylcoumarin
-
pH 7.5
0.139
procaspase-3
-
caspase-9 holoenzyme
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
acetyl-VEHD-7-amido-4-methylcoumarin
Homo sapiens
-
pH 7.5
0.2
acetyl-VEHD-7-amido-4-methylcoumarin
Homo sapiens
-
pH 6.5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000014
(3S,6S,10aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide
-
pH and temperature not specified in the publication
0.00233
(3S,6S,8aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydroindolizine-3-carboxamide
-
pH and temperature not specified in the publication
0.00006
(3S,6S,9aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide
-
pH and temperature not specified in the publication
0.000048
acetyl-AEVD-CHO
-
pH 7.5, 25C
0.00006
acetyl-DEVD-CHO
-
pH 7.5, 25C
0.000108
acetyl-IETD-CHO
-
pH 7.5, 25C
0.000508
acetyl-WEHD-CHO
-
pH 7.5, 25C
0.00097
acetyl-YVAD-CHO
-
pH 7.5, 25C
0.0171
benzyloxycarbonyl-VAD-fluoromethylketone
-
-
0.0142
benzyloxycarbonyl-VAE-fluoromethylketone
-
-
0.00058
L-alanyl-L-valyl-L-prolyl-L-isoleucinamide
-
pH and temperature not specified in the publication
0.0002
Zn2+
-
mutant C272A/C287A, pH 6.5, 37C
0.0007
Zn2+
-
mutant C272A, pH 6.5, 37C; mutant C287A/C239S, pH 6.5, 37C
0.0008
Zn2+
-
mutant C287A, pH 6.5, 37C; mutant H237A, pH 6.5, 37C
0.0012
Zn2+
-
mutant C239S, pH 6.5, 37C
0.0015
Zn2+
-
mutant C172A, pH 6.5, 37C
0.0018
Zn2+
-
wild-type enzyme, pH 6.5, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
contribution of the death receptor and mitochondrial (intrinsic) pathways to apoptosis in follicular lymphoma cells induced by the chimeric mouse-human anti-CD20 antibody rituximab, time course of caspase activation, overexpression of caspase-9 inhibits the rituximab-induced activation of effector proteases (caspase-3, caspase-6 and caspase-7), rituximab-induced release of cytochrome c and collapse of mitochondrial membrane potential regulated by caspase-9
additional information
-
increase in osteoblast apoptosis observed after 24 and 72 h treatment in response to the lowest dose of sodium fluoride (0.5 mg/l), osteoblast apoptosis also increased in response to higher doses, mRNA of caspase-9 increased in response to sodium fluoride treatment (5 mg/l) for 72 h, morphological and histochemical characterization of osteoblasts, cell proliferation and apoptosis assays, quantification of mRNA expression of caspase-3 and caspase-9 by real time PCR
additional information
-
knockdown of the cellular-FLICE inhibitory protein (c-FLIP) using small interfering RNA (siRNA) triggers ligand-independent caspase-9-dependent spontaneous apoptosis, proliferation of MCF-7 breast cancer cells decreased
additional information
-
protective effect of the herbal drug Hwanggunchungyitang (HGCYT) against activation of caspase-9 by Cd2+, activity of caspase-9 measured by colorimetric assay and Western Blot analysis
additional information
-
apoptotic mechanism of the flavanoid isorhamnetin, isorhamnetin induces mitochondria-dependent caspase activation cascade, caspase inhibitors block isorhamnetin-induced apoptosis, increased cleavage of caspase-9 shown by Western blot analyses of isorhamnetin-treated cells, cytotoxicity assay, TUNEL assay, DNA fragmentation assay, measurement of mitochondrial membrane potential
additional information
-
mechanisms of apoptosis induced by high linear energy transfer (LET) radiation, irradiation with X-rays, C-ion, or Fe-ion beams, apoptosis quantified with Hoechst 33342 staining, activation of caspase-3 analyzed by Western blot and flow cytometry, poly (ADP-ribose) polymerase (PARP) cleavage, caspase-9 inhibitor suppresses caspase-3 activation and induction of apoptosis, high linear energy transfer (LET) radiation enhances apoptosis by activation of caspase-3 through caspase-9, even in the presence of mp53 protein
additional information
-
hydrogen peroxide application leads to activation of caspase-9 and apoptosis, promoted interaction between caspase-9 and apoptotic protease-activating factor 1 (APAF-1), thiol-oxidant diamide reveals auto-cleavage of caspase-9 and interaction of caspase-9 and APAF-1, formation of disulfide-linked complexes facilitated, in vitro analysis of a mitochondria-free system, point mutation at C403 of caspase-9 impairs caspase-9 activation induced by H2O2, interaction with APAF-1 diminished by impaired disulfide formation, mutant analysis shows that oxidative modification of caspase-9 contributes to the formation of the apoptosome under oxidative stress
additional information
protein kinase DYRK1A is a negative regulator of the intrinsic apoptotic pathway in the developing retina, DYRK1A phosphorylates caspase-9 on threonine residue 125, phosphorylation crucial to protect retina cells from apoptotic cell death, dysregulation of the apoptotic response in differentiating neurons with an imbalance effects of DYRK1A gene-dosage participates in the neuropathology of diseases
additional information
analysis of oocytes from prophase I onwards, inhibition of caspase activity accelerates transition from metaphase I to metaphase II, caspase-9 and caspase-3 detected along the meiotic spindle, similar amounts of cleaved caspases in healthy and fragmented oocytes, caspase inhibition does not prevent doxorubicin-induced apoptosis, cleaved caspases probably dispensable for final oocyte death, potential involvement in the regulation of oocyte maturation
additional information
-
Western blot analysis reveals cordycepin-induced expression of caspase-9, activation of caspase-3 and caspase-7, but not of caspase-8 in a time- and dose-dependent manner, cordycepin-induced apoptosis acts through a caspase-9 and caspase-3 and caspase-7 dependent pathway
additional information
-
caspase-9 identified as a substrate of the protein kinase DYRK1A, in vitro translation and immunoprecipitation of FLAG-DYRK1A in absence or presence of kinase inhibitors analyzed, the kinase inhibitor harmine prevents inhibitory phosphorylation of caspase-9 on threonine residue 125, depletion of DYRK1A by RNA silencing inhibits phosphorylation of caspase-9 on Thr125 in cellular assays, co-expression analysis shows interaction between DYRK1A with caspase-9
additional information
-
RC-RNase-induced caspase-9/-3-mediated cytotoxicity in undifferentiated and differentiated cells, cell differentiation and adhesion assays, cell proliferation assays, caspase-9/-3-mediated cytotoxicity can be induced in differentiated cells that are pretreated with inhibitors of protein kinase C (PKC) or mitogen activated protein kinase (MEK), caspases-9/-3-mediated cytotoxicity in differentiated cells inhibited by protein kinase C (PKC) and the mitogen activated protein kinase (MEK) signaling pathways
additional information
-
mechanisms of apoptosis induced by ionizing radiation on cell lines with a different status of p53 (TP53 tumor suppressor gene), activity of initial caspases (-8 and -9) analyzed by Western-Blot of whole-cell lysates and mitochondrial fractions, cells lacking the p53 protein show activation of caspase-8 prior to activation of caspase-9, cells harboring the p53 protein show a simultaneous activation of both initial caspases, extrinsic (caspase-8 dependent) and intrinsic (caspase-9 dependent) pathways activated upon exposure ionizing radiation regardless to the status of p53 protein
additional information
-
mechanisms of apoptosis induced in response to marine sponge extracts of Polymastia janeirensis, flow cytometry analysis, assessment of glioma cell viability, dose-dependent increase in ROS production, inhibitor studies to determine whether the extracts activate the extrinsic or intrinsic pathways of apoptosis, marine sponge extracts of Polymastia janeirensis induce oxidative cell death mediated through the caspase-9 pathway
additional information
-
determination of caspase-9 auto-processing in a cell-free system, phosphorylation of caspase-9 analyzed by Western blot, phosphorylation of caspase-9 by casein kinase 2 (CK2) on a serine near the site of caspase-8 cleavage, CK2 modification of Ser348 on caspase-9 lowers the susceptibility of caspase-9 to cleavage but does not affect caspase-9 auto-processing, substitution of Ser348 abolishes phosphorylation but not cleavage, phosphatase inhibitors delay apoptosis induced by tumor necrosis factor (TNF)-alpha, inhibition of kinase activity or loss of the kinase accelerates apoptosis and promotes early caspase-9 activation in response to TNF-alpha, modification of pro-caspase-9 in the vicinity of its processing motif protects the protease from inappropriate activation by other caspases
additional information
-
caspase-9 is responsible for the activation of caspase-3 in differentiating myoblasts, decreased caspase-9 levels due to RNA interference prevents caspase-3 activation and impairs muscle differentiation, release of cytochrome c not observed, novel mechanism of caspase-9 activation during muscle differentiation, apoptotic nuclear morphology assessed by DAPI staining, quantification of muscle-cell differentiation, mitochondrial-membrane depolarisation, cell fractionation, immunoblotting
additional information
-
mechanisms of adenosine-induced apoptosis in human colonic cancer cells, cell viability, DNA laddering, expression analysis of adenosine receptors, overexpression of A2a adenosine receptors, determination of mitochondrial membrane potentials, adenosine disrupts mitochondrial membrane potentials and activates caspase-9 and caspase-3, but not caspase-8
additional information
value of an inducible caspase-9-based safety switch to halt an ongoing immune attack, retroviral transduction of T cells, induction and analysis of apoptosis, depletion of transduced T cells determined by flow cytometric analysis of GFP expression, in vivo assessment of the inducible caspase-9 suicide switch, immunohistochemistry, evaluation of this conditional safety switch in clinical trials of adoptive cell therapy
additional information
-
analysis of apoptosome inhibitors, improvement by chemical modifications for better increase of cellular penetration and efficient prevention of cell death, evaluation of cellular apoptosis by flow cytometry, immunohistochemistry, caspase activation assay
additional information
-
the poly-L-glutamic acid (PGA) derivative PGA-1 is capable of reducing hypoxia-induced apoptosis in primary culture cardiomyocytes
additional information
genotyping of caspase-9 by PCR analysis, control and patient sample genotype frequencies distributed according to Hardy-Weinberg equilibrium, clinical characteristics and genotypes, evaluation of a single nucleotide polymorphism (SNP) in the caspase-9 gene of multiple sclerosis patients from Southern Italy, presence of the G/G genotype identified as a higher risk factor in the analyzed multiple sclerosis (MS) population, differential caspase-9 production related to the severity of multiple sclerosis
additional information
-
proteomic analysis of caspase-9-associated protein complexes, one-dimensional gel electrophoresis and tandem mass spectrometry, 24 differential caspase-9 interactors identified, assigned to cytoskeletal organization, cell motility, catalytic activity, transcription and apoptosis, galectin-3, swiprosin-1 and the membrane-cytoskeleton linkers ezrin/radixin/moesin identified as novel caspase-9 interactors, co-immunoprecipitation and Western blot to confirm interaction of caspase-9 with identified binding partners
additional information
-
atorvastatin induces apoptosis in hepatic stellate cells (HSCs), atorvastatin-mediated apoptosis is blocked by co-application of mevalonic acid and U0126, an activator of the extracellular signal-regulated protein kinase (ERK1/2), increased activity of caspase-9 to 407% and of caspase-3 to 540% in cells treated with atorvastatin, flow cytometry, laser-scanning microscopy, Western blot, electrophoresis mobility shift assay, pathway of apoptosis induced by atorvastatin in hepatic stellate cells (HSCs) summarized
additional information
-
cytotoxiciy of Vibrio vulnificus cytolysin (VVC) analyzed by treatment of cell cultures with recombinant VVC protein (rVVC), recombinant Vibrio vulnificus cytolysin (rVVC) induces apoptosis in a time- and dose-dependent manner, apoptosis induced by recombinant Vibrio vulnificus cytolysin (rVVC) mediated by caspase-9 activation rather than caspase-8 activation
additional information
-
protective effects of cadmium on apoptosis induced by benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), inhibition of BPDE-induced apoptosis by cadmium is associated with downregulation of caspase-9 activation, cadmium-induced inhibition of apoptosis associated with downregulation of caspase-9 activation, 40% and 52% inhibition of apoptosis after pre-treatment of cells with 10 and 20 microM cadmium chloride, respectively
additional information
-
increased activity of caspase-9 during hypoxia, significant increase in the phophorylation on Ser196 during hypoxia, modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.2
-
mutant DELTA1-111
6.5
-
assay at
6.5 - 7
-
reaction with acetyl-VEHD-7-amido-4-methylcoumarin
7.2
-
mutant DELTA1-111/E306A/D315A
7.4
-
assay at
7.4
-
assay at
7.5
-
caspase activity assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
activity assay at
37
-
caspase activity assay at
37
-
caspase activity assay at
37
-
activity assay at
37
-
caspase-9 activity determined at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
high expression level
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
caspase-9 is highly expressed in tadpole brain during metamorphosis. Caspase-9 mRNA is expressed mainly in the ventricular area, a site of neuroblast proliferation. Caspase-9, a key members of the mitochondrial death pathway, is implicated in controlling the proliferative status of neuroblasts in the metamorphosing Xenopus brain. Modification of the expression during the critical period of metamorphosis alters the outcome of metamorphic neurogenesis, resulting in a modified brain phenotype in juvenile Xenopus
Manually annotated by BRENDA team
-
mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing wild-type p53
Manually annotated by BRENDA team
-
mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing p53-/-
Manually annotated by BRENDA team
-
of newborn piglets
Manually annotated by BRENDA team
-
of newborn piglet
Manually annotated by BRENDA team
-
mitochondrial fraction of cerebral tissue, hypoxia-treated, classified into a normoxic group and a hypoxic group
Manually annotated by BRENDA team
-
caspase-9 is released into the cerebrospinal fluid after severe traumatic brain injury
Manually annotated by BRENDA team
-
inhibition of caspase-9 enhances the viability of the CHO cells in both batch and fed-batch suspension cultures. Caspase-9 is possible involved in the apoptotic cell death in batch and fed-batch cultures of CHO cells
Manually annotated by BRENDA team
-
cochlear cell line HEI-OC1
Manually annotated by BRENDA team
-
caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
-
from cecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum. Caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
-
activity increases transiently at mid-late luteal phase
Manually annotated by BRENDA team
-
caspase-9 activity increases in the old corpus luteum at estrus, during the functional luteolysis
Manually annotated by BRENDA team
-
heat shock and tumor necrosis factor-alpha induce apoptosis in bovine preimplantation embryos through a caspase-9-dependent mechanism
Manually annotated by BRENDA team
-
mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing p53-/-; mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing wild-type p53
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
caspase-9 null mouse embryo fibroblast
Manually annotated by BRENDA team
-
human fibroblast GM03349
Manually annotated by BRENDA team
-
cell line HF1A3, wild-type, dominant negative caspase-9 overexpressing
Manually annotated by BRENDA team
-
cell line HF1A3, wild-type, dominant negative caspase-9 overexpressing
Manually annotated by BRENDA team
-
caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
-
caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
-
gingivial cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) protein by point mutation at codon 248
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
-
effect of the kinase inhibitor harmine on the phosphorylation of Thr125 and on endogenous caspase-9
Manually annotated by BRENDA team
-
treated with doxorubicin (2, 2.5, and 0.25 microg/ml in PBS), doxorubicin-induced cell death
Manually annotated by BRENDA team
-
primary cultures of, in vitro activation by atorvastatin, mevalonic acid and U0126, an activator of the extracellular signal-regulated protein kinase (ERK1/2)
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
primary cultures of, in vitro activation by atorvastatin, mevalonic acid and U0126, an activator of the extracellular signal-regulated protein kinase (ERK1/2)
-
Manually annotated by BRENDA team
-
undifferentiated and differentiated cells, differentiation induced by phorbol-12-myristate-13-acetate (TPA)
Manually annotated by BRENDA team
-
null mutant of protein p53
Manually annotated by BRENDA team
-
cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37C for 4 h, cell viability assay
Manually annotated by BRENDA team
-
caspase-9-deficient cells reveal strongly impaired apoptosis, caspase activation, and mitochondrial membrane depolarization upon CD95 triggering. Caspase-9-deficient Jurkat line JMR will prove a very useful tool for further analysis of cell death mechanisms in the absence of apoptosome function
Manually annotated by BRENDA team
-
caspase-9 is indispensable for drug-induced apoptosis in cancer cells. Caspase-9 is not only required for loss of mitochondrial membrane potential but also for caspase-2 activation
Manually annotated by BRENDA team
-
proximal tubular epithelial cell
Manually annotated by BRENDA team
-
proximal tubule cell
Manually annotated by BRENDA team
-
isolated from 5-week-old female C57BL/6 mice, intraperitoneal injection of isorhamnetin (0.1 or 0.5 mg/kg) four days after tumor inoculation
Manually annotated by BRENDA team
-
caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
-
increased caspase 9 activity in lymphoblasts with heterozygous and homozygous Huntington's disease mutation; increased caspase-9 activity in lymphoblasts with heterozygous and homozygous Huntington's disease mutation
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
human H460 NSCLC cells with and without cytochrome c/(d)ATP-induced activation of apoptosis
Manually annotated by BRENDA team
-
no difference in caspase-9 activity in oocytes compared with zygotes. Cultures of oocytes in staurosporine increases the activity of caspase-9
Manually annotated by BRENDA team
immature, germinal vesicle stage oocytes, GV-oocytes
Manually annotated by BRENDA team
-
wild-type and SOD-antisense
Manually annotated by BRENDA team
-
incubated with 0.5-30 mg/l of sodium fluoride (NaF)
Manually annotated by BRENDA team
Mus musculus BDF1
-
mastocytoma
-
Manually annotated by BRENDA team
-
caspase-9, which is activated by infection with virulent Mycobacterium tuberculosis, contributes to the inhibition of necrosis of the infected host cells, through suppression of generation of intracellular reactive oxygen species
Manually annotated by BRENDA team
developing and adult
Manually annotated by BRENDA team
-
Immunohistochemical locaization of enzyme in outer retina layers, overview
Manually annotated by BRENDA team
-
treated with doxycycline (2 microg/ml in PBS)
Manually annotated by BRENDA team
-
cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37C for 4 h, cell viability assay
Manually annotated by BRENDA team
-
cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37C for 4 h, cell viability assay
Manually annotated by BRENDA team
B6 mice, modified by retroviral transduction
Manually annotated by BRENDA team
retroviral transduction of
Manually annotated by BRENDA team
-
ischemia-reperfusion of the testis results in germ-cell-specific apoptosis and a reduction in daily sperm production. Oxidative stress products accumulate in the testis following ischemia-reperfusion and demonstrate that the observed germ-cell-specific apoptosis is stimulated through a mitochondrial caspase-9-dependent pathway
Manually annotated by BRENDA team
-
treated with different concentrations of marine sponge extracts of Polymastia janeirensis
Manually annotated by BRENDA team
-
treated with doxorubicin (2, 2.5, and 0.25 microg/ml in PBS), doxorubicin-induced cell death
Manually annotated by BRENDA team
-
transfected with vectors carrying caspase-9 point mutations and GFP-DYRK1A, immunofluorescence staining
Manually annotated by BRENDA team
-
treated with doxorubicin (2, 2.5, and 0.25 microg/ml in PBS), doxorubicin-induced cell death
Manually annotated by BRENDA team
-
no difference in caspase-9 activity in oocytes compared with zygotes
Manually annotated by BRENDA team
-
intact protein p53
Manually annotated by BRENDA team
additional information
-
Lyccasp9 is constitutively ubiquitously expressed, although expression levels vary from tissue to tissue, real-time PCR expression analysis
Manually annotated by BRENDA team
additional information
-
immunohistochemic expression analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
intracellular localization of caspase-9 in germinal vesicle stage oocytes analyzed, faint and homogeneous distribution, fluorescent staining
Manually annotated by BRENDA team
-
mitochondrial fraction of cerebral tissue
Manually annotated by BRENDA team
intracellular localization of caspase-9 in germinal vesicle stage oocytes analyzed, distribution related to chromatin configuration
Manually annotated by BRENDA team
-
phosphorylation of caspase-9 by DYRK1A involves co-localization to the nucleus
Manually annotated by BRENDA team
additional information
-
immunohistochemic expression analysis, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35000
-
processed caspase-9 protein, SDS-PAGE
699829
37000
-
processed caspase-9 protein, SDS-PAGE
699829
47000
-
un-processed caspase-9 protein, SDS-PAGE
699829
52000
-
pro-caspase-9, Western blot, increased in hypoxic animals
700460
55000
-
full-length caspase-9, Western blot analysis
695657
68000
-
observed molecular weight of caspase-9 by tandem mass spectrometry in cell lysates with and without cytochrome c/dATP treatment
699829
69200
-
calculated molecular weight of caspase-9 by tandem mass spectrometry in cell lysates with and without cytochrome c/dATP treatment
699829
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 46200, calculation from nucleotide sequence
?
-
x * 30000, caspase 9S, SDS-PAGE
?
-
x * 35000, processed caspase-9 protein, SDS-PAGE; x * 37000, processed caspase-9 protein, SDS-PAGE; x * 47000, un-processed caspase-9 protein, SDS-PAGE; x * 68000, observed molecular weight of caspase-9 by tandem mass spectrometry in cell lysates with and without cytochrome c/dATP treatment; x * 69200, calculated molecular weight of caspase-9 by tandem mass spectrometry in cell lysates with and without cytochrome c/dATP treatment
dimer
-
apoptosome activates caspase-9 by dimerization
dimer
-
processed caspase-9 can be displaced from the apoptosome by additional molecules of procaspase-9, resulting in release of cleaved caspase-9, which can form active dimers
dimer
-
dimerisation of caspase-9 results in rapid autocatalytic cleavage, yielding caspase-9 (p35/p12)
homodimer
-
gel filtration and SDS-PAGE, caspases are functional as homodimers of monomeric units that comprise an N-terminal prodomain and a catalytic large and small subunit connected by an intersubunit linker. The zymogen (uncleaved) caspase-9 as a monomer has very low activity, which is increased upon dimerization
additional information
-
proteolytic activity of caspase-9 in a complex with APAF-1 is several orders of magnitude higher than that of the free enzyme. Thus, this complex functions as a holoenzyme in which caspase-9 is the catalytic subunit and APAF-1 its allosteric regulator
additional information
-
the caspase family signature histidine active-site H236SQYDCCVVIMLSHG250, the cysteine active-site K290PKLFFIQACGG301 and the caspase 9 characteristic pentapeptide active-site QACGG are located in the p20 domain
additional information
-
the zymogen caspase-9 has very low activity as a monomer. Activity increases upon dimerization and increases even more profoundly upon interaction with the apoptosome. Caspase-9 does not require intersubunit cleavage for activation
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nitrosylation
-
nitrosylation of caspase-9 at C163 is dependent, at least in part, on subcellular localization. 68% of the procaspase-9 in mitochondria is nitrosylated and 11% of the procaspase-9 in the cytoplasm in unstimulated 10C9 human B cells
phosphoprotein
-
the enzyme is proteolytically processed into an active cysteine protease
phosphoprotein
-
CPP32 processes pro-Mch6 preferentially at Asp330 to generate two subunits of molecular masses 37000 Da and 10000 Da. Granzyme B can also process pro-Mch6 but at a site N-terminal to that cleaved by CPP32 and generates two cleavage products, a large 35000 Da product and a small 12000 Da product
phosphoprotein
-
caspase-9 is phosphorylated on Thr125 in a MEK172-dependent manner in vivo, efficiently phosphorylated on Thr125 by ERK in vitro. Phosphorylation of Thr125 on caspase-9 may be an important mechanism through which growth factor and survival signals that activate the ERK MAPK pathway can inhibit apoptosis
phosphoprotein
-
kinase Akt and p21-Ras, an Akt activator, induce phosphorylation of pro-caspase-9 in cells. Akt phosphorylates recombinant caspase-9 in vitro on Ser196 and inhibits its protease activity. Mutant pro-caspase9(Ser196Ala) is resistant to Akt-mediated phosphorylation
phosphoprotein
-
the kinases PKB-Akt and ERK2 are involved in the phosphorylation of human caspase-9 at Ser196 and Thr125, respectively
phosphoprotein
-
caspase-9 is phosphorylated at Thr125 in cells by ERK1/2 but not by c-Jun N-terminal kinases or p38 MAPKs
phosphoprotein
-
caspase-9 is regulated during cell cycle through periodic phosphorylation at an inhibitory site, Thr125. This site is phosphorylated by CDK1/cyclin B1 during mitosis and in response to microtubule poisons that arrest cells at this stage of the cell cyclce. Phosphorylation of caspase-9 at Thr125 protects mitoctic cells against apoptosis
phosphoprotein
-
phophorylation of caspase-9 at the inhibitory threonine residue 125 catalyzed by the protein kinase DYRK1A
proteolytic modification
-
the enzyme is synthesized as a 46000 Da precursor
proteolytic modification
-
Apaf-1-mediated processing of procaspase-9 occurs at Asp315 by an intrinsic autocatalytic activity of procaspase-9 itself. Apaf-1 can form oligomers and may facilitate procaspase-9 autoactivation by oligomerizing its precursor molecules
proteolytic modification
-
activation site is PEPD-/- (P4,P4,P2,P1)
proteolytic modification
-
proteolytic processing is associated with the removal of a leader sequence, processing by caspase-3 at amino acid 130 and 330. Autolytic processing at amino acid 307 and 315; proteolytic processing is associiated with the removal of a leader sequence, processing by caspase-3 at amino acid 130 and 330. Autolytic processing at amino acid 307 and 315
proteolytic modification
-
activation of caspase-9 via proteolytic cleavage
proteolytic modification
-
when bound to the apoptosome, caspase-9 is processed at Asp315, resulting in a CARD-large subunit portion of the enzyme and a small subunit beginning with the N-terminal sequence of ATPF. Proteolytic removal of the CARD domain from the large subunit, which results in decreased activity, is also observed. Processed caspase-9 can be displaced from the apoptosome by additional molecules of procaspase-9, resulting in release of cleaved caspase-9, which can form active dimers
proteolytic modification
-
initiator pro-caspases exist as monomers and possess long pro-domains. These pro-domains contain specific protein-protein interaction sites that are crucial for initiator caspase activation. The pro-domain of caspases-9 contain a caspase activation recruitment domain (CARD) motif. Release of cytochrome-c and other proapoptotic proteins into the cytosol results in the formation of the apoptosome, the activation platform for initiator caspase-9. Flexible linkers connect the caspase activation recruitment domain (CARD) with the large subunit and the large subunit with the small subunit. The linker between the large and small subunits contains the caspase-9 auto-cleavage site (D315). Cleavage at this site generates the p35/p12 form of caspase-9. The p35/p12 form can be further processed by caspase-3 by cleavage at site D330, generating caspase-9
proteolytic modification
-
the uncleaved monomeric zymogen of caspase-9 has very low activity, which is increased upon dimerization. In dimeric caspase-9 cleavage at a specific aspartate residue in the intersubuint linker between the large and small subunits is required for caspase-9 to attain increased activity
phosphoprotein
phophorylation of the inhibitory threonine residue 125, catalyzed by the protein kinase DYRK1A
phosphoprotein
-
phosphorylation of caspase-9 by casein kinase 2 (CK2) on a serine near the site of caspase-8 cleavage, TNF receptor cross-linking promotes dephosphorylation of caspase-9, phosphorylation of caspase-9 by casein kinase 2 (CK2) decreases its susceptibility to cleavage by active caspase-8
proteolytic modification
-
incubation of cytosol from rat kidney proximal tubule cells with cytochrome c and dATP results in rapid autocatalytic processing of procaspase-9 from 50000 Da to 38000 Da size fragment. Cytochrome c concentration influences the production of alternatively processed forms of caspase-9. At lower cytochrome c concentration, two fragments of caspase-9 of the size 38000 Da and 40000 Da are produced. At higher concentrations of cytochrome c only 38000 Da fragment is detected
phosphoprotein
-
phosphorylation on Ser196 in hypoxic animals increased
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gel filtration
-
gel filtration, SDS-PAGE
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain B21(DE3) inclusion bodies by solubilization with guanidine hydrochloride and dialysis, followed by nickel affinity and anion exchange chromatography
-
recombinant His6-tagged enzyme
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography
-
gel filtration, SDS-PAGE, recombinant protein
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
gene CSP9, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in Escherichia coli strain BL21(DE3)
-
caspase-9 inactivated by mutation at the catalytic domain, generation of dominant negative caspase-9 overexpressing cell lines, expression in Escherichia coli, follicular lymphoma cells transformed with the lentiviral vector pWPI-IRES-GFP
-
caspase-9 splice variant Casp9-gamma contains only a caspase recruitment domain and lacks the catalytic domain, expression in 293T cells.Casp9-gamma does not promote apoptosis when overexpressed in 293T cells
-
caspase-9S is cloned from human liver cDNA
-
expressed in Escherichia coli, recombinant protein, pcDNA3, pET28a, pEGFP vectors
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain B21(DE3) in incusion bodies
-
human caspase-9 (wild type or mutant R10A) are subcloned into the pIND expression plasmid before cotransfection of recombinant pIND and pVgRXR into U2OS cells
-
naturally occuring variant caspase-9S, that is missing most of the large subunit of caspase-9
-
recombinant expression of His6-tagged holoenzyme in Escherichia coli strain BL21(DE3), recombinantindividual expression of large and small subunits in inclusion bodies
-
gene Lyccasp9, DNA and maino acid sequence determination and analysis, full-length cDNA of Lyccasp9 is 2595 bp with an open reading frame of 1314 bp encoding a polypeptide of 437 amino acids, which includes a 90-amino acids caspase recruitment domain (CARD, residues 1-90), a 133-amino acids p20 domain (residues 171-303) with two putative caspase family histidine and cysteine active sites, as well as an 87-amino acids p10 domain (residues 348-435)
-
adenovirus expression, AdshRNA-C9 and AdshRNA-eGFP vectors, AdBcl-xL and AdNull adenoviral vectors
-
B6 splenocytes modified by retroviral transduction, truncated caspase-9 molecule genetically coupled to a modified human FK506-binding protein (FKBPF36V) by generating the iCasp9M-construct, iCasp9M construct (safety switch) and enhanced GFP used for transformation
expressed in Escherichia coli
expressed in Escherichia coli, pcmyc vector, pFLAG-CTC vector to generate FLAG-tagged caspase-9 construct
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cadmium induces the enzyme
-
siRNA Si Casp-9-1 efficiently inhibits caspase-9 expression
-
trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway, molecular mechanism, overview
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
optical sensor for the detection of caspase-9 in a single cell. LEHD-7-amido-4-methylcoumarin covalently attached on the nanoprobe tip of the optical sensor is cleaved during apoptosis by caspase-9 generating free 7-amino-4-methylcoumarin
C172A
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C239S
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C272A
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C272A/C287A
-
the mutant enzyme shows highly reduced zinc binding compared to the wild-type enzyme
C287A
-
immunofluorescence staining of cells transiently transfected with vectors encoding caspase-9 point mutation
C287A
-
the active site mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C287A/C239S
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C403S
-
point mutation at C403 of caspase-9 impairs its activation mediated by H2O2, interaction with APAF-1 diminished through the abolition of disulfide formation, weaker association between cytochrome c and the C403S mutant than that between cytochrome c and wild-type caspase-9
DELTA1-111
-
a truncated form of procaspase-9 missing the first 111 amino acids, and a variety of mutants derived therefrom are expressed in Echerichia coli inclusion bodies. Upon refolding to active enzyme, DELTA1-111 procaspase-9 and mutants are recovered at purity greater than 95% with a final yield of 20-35 mg/L cell culture. the active procaspaseretains its prosegment, while undergoing major auto processing at ASp315 and a minor cleavage at Glu306
DELTA1-111/DELTAA316-D330
-
activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is 6fold higher than the activity of mutant DELTA1-111; activity with acetyl-LEHD-7-amido-4-trifluoromethylcoumarin is 6fold higher than the activity of mutant DELTA1-111
DELTA1-111/E306A/D315A
-
E306A/D315A mutation blocks autoprocessing and shifts pH optimum from pH 6.2 for DELTA1-111 to pH 7.2. Activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is identical to the activity of mutant DELTA1-111
DELTA1-111/E306D/D315A
-
activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is 90% of the activity of mutant DELTA1-111; activity with acetyl-LEHD-7-amido-4-trifluoromethylcoumarin is 90% of the activity of mutant DELTA1-111
DELTA1-111/E306D/DELTAA316-D330
-
activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is 7.6fold higher than the activity of mutant DELTA1-111; activity with acetyl-LEHD-7-amido-4-trifluoromethylcoumarin is 7.6fold higher than the activity of mutant DELTA1-111
T125A/C287A
-
site-directed mutagenesis, immunofluorescence staining of cells transiently transfected with vectors encoding caspase-9 double mutant
C299G
-
site-directed mutagenesis, the mutant displays significantly decreased proteolytic activity compared to the wild-type enzyme
H249D
-
site-directed mutagenesis, the mutant displays significantly decreased proteolytic activity compared to the wild-type enzyme
S348A
-
introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
S348G
-
introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
S348V
-
introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
S350A
-
introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
H237A
-
the active site mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
additional information
-
caspase-9S is a naturally occuring variant of caspase-9 that is missing most of the large subunit of caspase-9, including the catalytic site, but has the intact prodomain and small subunit. Caspase-9S does not show apoptotic activity in transfection analysis. Overexpression of caspase 9S inhibits apoptosis induced by caspase-9. Caspase-9S inhibits apoptosis induced by tumor necrosis factor alpha, TNF factor-related apoptosis-inducing ligand, Bax, or fas-associated death domain-containing protein as well as the combination of Apaf-1 and caspase-9
additional information
-
engineering of a leucine-zipper-linked dimeric caspase-9 (LZ-C9). Removal of the caspase recruitment domain of procaspase-9 and replacement with the leucine-zipper dimerization domain of the transcriptional factor GCN4. A six residue linker is added in between the leucine zipper and the beginning of the catalytic domain of caspase-9. LZ-C9 is more active than the caspase-9 holoenzyme for acetyl-LEHD-7-amido-4-trifluoromethyl coumarin but much less active the the caspase-9 holoenzyme for the physiological substrate procaspase-3; engineering of a leucine-zipper-linked dimeric caspase-9 (LZ-C9). Removal of the caspase recruitment domain of procaspase-9 and replacement with the leucine-zipper dimerization domain of the transcriptional factor GCN4. A six residue linker is added in between the leucine zipper and the beginning of the catalytic domain of caspase-9. LZ-C9 is more active than the caspase-9 holoenzyme for acetyl-LEHD-7-amido-4-trifluoromethylcoumarin but much less active the the caspase-9 holoenzyme for the physiological substrate procaspase-3
additional information
-
knockdown of caspase-9 expression by specific siRNA
L228V
-
site-directed mutagenesis
additional information
plasmids pGFP-CASP9 WT/C287/T125 and pGST-CASP9 WT/T125 generated by site-directed mutagenesis
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain B21(DE3) incusion bodies by solubilization with guanidine hydrochloride and dialysis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
inhibition of the caspase-9 activity would render opportunity to treat patients suffering from neurological diseases such as stroke, neurodegenerative diseases or brain injury caused by hypoxia
medicine
-
mechanisms of adenosine-induced apoptosis in human colonic cancer cells
medicine
analysis of a single nucleotide polymorphism (SNP) in the caspase-9 gene in relation to susceptibility to multiple sclerosis (MS)
medicine
-
there is a weak correlation between activated caspase-9 and poor neurologic outcome after severe traumatic brain injury
pharmacology
-
rituximab-induced apoptosis highly dependent on caspase-9 activation, regulated by Bcl-xL expression
pharmacology
-
the cellular-FLICE inhibitory protein (c-FLIP) analyzed as a potential therapeutic target for breast cancers
pharmacology
-
studies on mechanisms of apoptosis induced by high linear energy transfer (LET) radiation
pharmacology
-
studies on molecular mechanisms of caspase-9 activation mediated by reactive oxygen species (ROS)
pharmacology
-
studies on mechanisms of apoptosis induced by ionizing radiation in human leukaemic cells with a different status of p53 (TP53 tumor suppressor gene)
pharmacology
-
drug development, studies on mechanisms of apoptosis activated in response to marine sponge extracts of Polymastia janeirensis
pharmacology
-
analysis and improvement of apoptosome inhibitors
medicine
-
caspase-9 is a target for development of therapeutic approaches for histamine-related diseases
medicine
dysregulation of the apoptotic response in differentiating neurons participates in the neuropathology of diseases that display with an imbalance of DYRK1A gene-dosage
medicine
effectiveness and specificity of an inducible caspase 9-based safety switch system, to halt an ongoing immune attack, reduction of the risk of severe graft-vs-host disease, murine model for cell therapy-induced type I diabetes
pharmacology
-
therapeutic usefulness of the herbal drug Hwanggunchungyitang (HGCYT) against cadmium (Cd2+)-induced activation of caspase-9
pharmacology
-
in vitro analysis of apoptotic mechanism of isorhamnetin in Lewis lung cancer (LLC) cells, in vivo anti-cancer efficacy
pharmacology
-
studies on the mechanism of cordycepin-induced apoptosis in MA-10 Leydig tumor cells
medicine
Mus musculus BDF1
-
caspase-9 is a target for development of therapeutic approaches for histamine-related diseases
-
pharmacology
-
NaF-induced apoptosis of osteoblasts, in vitro studies, pronounced negative effect of NaF treatment on indices of survival of osteoblasts, decreased proliferation, increased apoptosis and increased caspase-3 and caspase-9 mRNA