Protein Casp3

URN urn:agi-llid:836
Connectivity 1893
Name Casp3
Description caspase 3
Notes A significant positive correlation between in-situ active caspase-3 in the sperm midpiece and DNA fragmentation was observed in the low motility fractions of patients. A significant positive correlation between in-situ active caspase-3 in the sperm midpiece and DNA fragmentation was observed in the low motility fractions of patients. A soluble proform of caspase 3 containing a fortuitous mutation (W206R) is inactive when incubated with recombinant human caspase 8 and therefore can serve as a useful reagent to test the efficacy of caspase 8 inhibitors. Absence of active caspase 3-positive nasopharyngeal carcinoma predicts rapid fatal outcome. Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells. Apoptosis marker activated caspase-3 was analysed by immunohistochemistry, during the production of collagen type II, the adhesion and signal transduction receptor beta1-integrin. Apoptotic cells secrete chemotactic factors that stimulate the attraction of monocytic cells and primary macrophages. The activation of caspase-3 in the apoptotic cell was found to be required for the release of these chemotactic factors. BAP31 and caspase 3 are cleaved in a process involving capsase 8 in the mitochondrial membrane during apoptosis. Both oleandrin and radiation share a caspase-3 dependent mechanism of apoptosis in the PC-3 human prostate cacncer cell line. CASP3 induced by H202 was completely blocked by Z-VAD-fmk. CASP3 is activated in the oxidative stress-induced apoptosis in tendon fibroblasts in vitro. CASP3 was expressed in the same tissues as its murine counterpart. Caspase 1 involvement in monocyte lysis induced by Actinobacillus actinomycetemcomitans leukotoxin. Caspase 3 activation associated with cellular prion is closely related to its ability to undergo endocytosis. This is, to our knowledge, the first direct description of an endocytosis-dependent PrP(c)-associated function. Caspase 3 activation is a prominent feature in periodontitis-associated tissue injury. Caspase 3 has a role in proteolysis of the N-terminal cytoplasmic domain of the human erythroid anion exchanger 1 (band 3). Caspase 3 plays a important role in apoptotic process of mesothelioma cells. Caspase 3-mediated cell death is central to the biological control of antigen-independent expansion of recent thymic emigrants from human cord blood. Caspase 3-mediated inactivation of rac GTPases promotes drug-induced apoptosis in human lymphoma cells. Caspase-3 activation in human disease can play a prominent role in localized cellular degenerative processes without causing nuclear or cell death. Caspase-3 dependent apoptosis occurs in human granulosa cells and activates when follicles begin to leave the resting pool. Caspase-3 is activated in oxidized low-density lipoprotein (ox-LDL) induces apoptosis in endothelial cells. Caspase-3 is frequently overexpressed in hepatocellular carcinomas and is associated with high serum levels of alpha-fetoprotein. Caspase-3 mediates a mitochondrial amplification loop that is required for the optimal release of cytochrome c, mitochondrial permeability shift transition, & cell death during apoptosis induced by treatment with the microtubule-damaging agent paclitaxel. Caspase-cleaved amyloid precursor protein and activated caspase-3 are co-localized in the granules of granulovacuolar degeneration in Alzheimer's disease and Down's syndrome brain. Chemical substances derived from the primary foci and metastatic microenvironment can inhibit the growth of metastatic cells by enhancing Caspase-3 expression and diminishing FasL expression in gastric cancer. Clinical significance of caspase-3 expression in pathologic-stage I, nonsmall-cell lung cancer. Data report that human oocytes and fragmenting preimplantation embryos possess transcripts encoding Harakiri and caspase-3. Data show that endoplasmic reticulum stress induced by thapsigargin not only activated the apoptosis effector caspase-3 but also caused a large and prolonged increase in the activity of glycogen synthase kinase-3beta. Data suggest that increased intrathecal release of Fas, but not FasL or caspase 3, in the cerebrospinal fluid of infants with hydrocephalus may serve as an indicator of brain injury from progressive ventricular dilatation. Dispensable for the execution of apoptosis in a metastatic melanoma cell line. Enzyme activation of caspase-3 was observed in apoptosis of K562 human cell line. Evidence indicates that casp3 activated by ricin acts on BAT3 at the caspase cleavage site, DEQD(1001) to release a C-terminal fragment designated CTF-131, which induces phosphatidylserine exposure, cell rounding, and chromatin condensation as ricin does. Expression correlates with intensity of apoptosis in colorectal adenocarcinoma. Expression levels of apoptosis-related proteins caspase 3, Bcl-2, and PI9 predict clinical outcome in anaplastic large cell lymphoma. Gossypol induced complete cytochrome c release from mitochondria amd increased caspases-3 and -9 activity in large cell lymphoma cells. High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict favorable clinical outcome. Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes. IFN-gamma-activated monocytes may induce reactive oxygen metabolites in retinal pigment epithelial(RPE) cells through cell-to-cell contact and promote HRPE cell apoptosis via caspase-3 activation. IFN-gamma-mediated caspase-3 activation and C. burnetii killing depend on the expression of membrane TNF. IGF-I activates specific apoptotic pathways (Caspase-3 activation, Annexin-V binding and DNA degradation in an osteosarcoma cell line. IL-15 does not increase IL-1alpha or IL-1beta production but induces IL-1Ra release, increases myeloid cell differentiation factor-1 stability, decreases the activity of caspase-3 and caspase-8, resulting in an inhibition of vimentin cleavage. Identification of high caspase-3 mRNA expression as a unique signature profile for extremely old individuals. In Jurkat cells caspase-3 is a component of the death-inducing signaling complex that colocalizes in lipid rafts with caspase-8, where caspase-3 activity is required for complete caspase-8 activation following Fas cross-linking. In Kennedy syndrome, phosphorylation of the polyglutamine-expanded form of androgen receptor regulates its cleavage by caspase-3 and enhances cell death. Inhibition of the Src-family tyrosine kinases activity by PP2 and of caspase-3 by Z-DEVD-FMK reverses apoptosis. MCF-7 tumor cells are deficient in CASP3 and instead have TNF-alpha-induced apoptosis. Mcl-1L degradation by either GrB or caspase-3 interferes with Bim sequestration by Mcl-1L. Neutrophils isolated from cirrhosis patients exhibited a decreased viability and a marked accelerated apoptosis and significantly higher caspase-3 activity. Overexpression of antiapoptotic proteins Bcl-2 and Bcl-X(L) and down-regulation of caspase-3 activity may be associated with cisplatin resistance in human ovarian cancer. PKCdelta-dependent phosphorylation of caspase-3 is involved in the regulation of monocyte life span. Presentation of nitric oxide regulates monocyte survival through effects on this enzyme and caspase-9 activation. Pro-CASP3 moved to the the mitochondria of U937 cells during TPA-induced differentiation. Role of nuclear PKC delta in mediating caspase-3-upregulation in Jurkat T leukemic cells exposed to ionizing radiation. Selective inhibition of dipeptidyl peptidase I, not caspases, prevents the partial processing of procaspase-3 in CD3-activated human CD8(+) T lymphocytes. Stx1 and LPS trigger DNA fragmentation and caspase-3 activation, as evidenced by the cleavage of poly(ADP-ribose) polymerase (PARP). Synthetic activation of inducible caspase-3, but not of caspase-8, resulted in apoptosis in glioma cell lines. Taken together, our data suggested that the JNK/c-Jun signaling cascade plays a crucial role in Cd-induced neuronal cell apoptosis and provides a molecular linkage between oxidative stress and neuronal apoptosis. The antiapoptotic property of Hualpha-Syn in neuronal cell lines is associated with the attenuation of caspase-3 activity without affecting the caspase-9 activity or the levels of cleaved, active caspase-3. The apoptosis resistance of mdr cells is not related to the abnormality of CPP32 but the upstream of caspase, the fact of which indicates promising prospect of the research on reversion of mdr cells using CPP32 as target. The crystal structure of the binding site of caspase-3 reveals critical side chain movements in a hydrophobic pocket. The positions of these side chains may have implications for the directed design of inhibitors of caspase-3 or caspase-7. The increased ratio of Bax/Bcl-2 proteins after Epigallocatechin-3-gallate may lead to activation of caxpaxe-3, leading to apoptosis. The significant expression of caspase-3 that occurs in monocytes during serum-deprived induction of apoptosis can be down-regulated to baseline levels by addition of platelets. These data suggest that D4-GDI of Rho family GTPase may be regulated during apoptosis through the caspase-3 mediated cleavage of the GDI protein. These data suggest that increased proneness to caspase activation in lymphocytes could reflect an ongoing systemic response in neurodegenerative disease with pathogenetic implications. These findings provide biological evidence showing that (+)-alpha-tocopherol can amplify the apoptotic response by up-regulating the expression of pro-caspase-3. This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein. Transfected caspase-3 is involved in the reduction of Akt level, and its involvement is mediated through caspase-9 activation. We conclude that the changes in the level of caspase-3 and survivin play an important role in the transformation from normal gastric mucosa to gastric cancer. Activated by coxsackievirus B3 (CVB3) infections and occurred in cells expressing full length CAR. Activated in normal erythropoiesis and in erythroblasts in culture. Activation of caspase-3 by the Dot/Icm virulence system of Legionella pneumophila is essential for halting biogenesis of the L. pneumophila-containing phagosome through the endosomal/lysosomal pathway. Apoptosis was preceded by proteolytic cleavage of caspases 2, 3, and 7, and wild type STAT1 also induced cleavage of caspase 7. Calcium could favour a necrotic mechanism by inducing the generation of a form of caspase 3 insensitive to mitochondrial activation. Caspase 3 activation and apoptosis are blocked by LIGHT protein in hepatocytes. Caspase 3 cleaves CDC6 during apoptosis, which prevents wounded cell from replicating and facilitates death. Caspase 3 exists in microparticles from endothelial cells and may be associated with caspase 3 activation unrelated to apoptosis. Caspase 3 has a role in cell death through apoptosis induced by ursolic acid. Caspase 3 has a role in damaging mitochondrial function and generating reactive oxygen species after activation by cytochrome c. Caspase 3-independent function of Bak in the TNF-alpha-induced apoptotic pathway. Caspase 3-mediated focal adhesion kinase processing in human ovarian cancer cells: possible regulation by X-linked inhibitor of apoptosis protein. Caspase-3 activation, mitochondrial respiratory function and cytochrome c release have roles in induction of apoptosis by ceramides. Caspase-3 as a key effector of neuronal apoptosis in pneumococcal meningitis. Caspase-3 is crucial for the differentiation of bone marrow stromal stem cells by influencing TGF-beta/Smad2 pathway and cell cycle progression. Caspase-3 is essential for efficient induction of apoptosis by staurosporine, but not for mitochondrial steps that occur earlier in the pathway. Caspase-3 may participate in the regulation mechanism of lymphoma cel apoptosis. Caspase-3 was upregulated in a region-specific manner with marked activation in the selectively vulnerable hippocampal after cerebral ischemia. Caspase-3-mediated proteolysis of FAK, an anti-apoptotic protein, is regulated by hsp72. Caspase-8 and -3 have roles in human mast cell apoptosis induction by Pseudomonas aeruginosa exotoxin A. Ceramide increases oxidative damage by inhibition of ROS scavenging ability through caspase-3-dependent proteolysis of catalase. Determination of levels of caspase-3 expression in breast tumor samples and to determine whether alterations in its expression can affect their ability to undergo apoptosis. Existence of a regulatory mechanism of protein stability and PTEN-protein interactions during apoptosis, executed by caspase-3 in a PTEN phosphorylation-regulated manner. Glc-oxLDL increases TUNEL positivity and caspase-3 activation of human coronary smooth muscle cells. Granule pools of Zn may be distinct from those regulating activation of procaspase-3 and NF-kappaB. Granzyme B targets a highly restricted range of substrates and orchestrates cellular demolition largely through activation of caspase-3. Hypoxia caused epithelial cell death induced by caspase-3-like activity-dependent apoptosis. In neutrophils, functional expression of caspase-3 in neutrophils may be regulated during ontogeny. Induced and utilized by human Astrovirus Yuc8 to promote processing of the capsid precursor and dissemination of the viral particles in CAC0-2 cells. Induction of ceramide accumulation by various triggers of ceramide generation triggered the activation of caspase-3. Investigation of molecular mechanism of MPO-mediated apoptosis and caspase-3 activation. MRNA and protein expression of this enzyme are examined in breast cancer to determine level of apoptosis. Mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults. One or more distinct cellular mechanisms regulate Bid cleavage by caspases 8 and 3 in situ. P38-MAPK can directly phosphorylate and inhibit the activities of caspase-8 and caspase-3 and thereby hinder neutrophil apoptosis, and, in so doing, regulate the inflammatory response. Procaspase-2S-mediated anti-apoptotic effects are associated with inhibition of the processing and activation of procaspase-3 in VP-16-treated cells. Removal of N-terminal domains of Bid by caspase-8 and Mcl-1 by caspase-3 enables the maximal mitochondrial perturbation that potentiates TRAIL-induced apoptosis. Required for Parvovirus B19 virus-induced apoptosis in primary hepatocytes and hepatocellular carcinoma cell line HepG2. Required for Sars virus 7a protein induction of apoptosis in cell lines from different organs. Results suggest that Anaplasma phagocytophilum inhibits human neutrophil apoptosis via transcriptional upregulation of bfl-1 and inhibition of mitochondria-mediated activation of caspase 3. Results suggest that IGF-1/PI-3 kinase inhibited C2-ceramide-induced apoptosis due to relieving oxidative damage, which resulted from the inhibition of catalase by activated caspase-3. Results suggest that active caspase-3 is translocated in association with a substrate-like protein(s) from the cytoplasm into the nucleus during progression through apoptosis. Results suggest that matrix metalloproteinase-9 and matrix metalloproteinase-2 contribute to caspase-mediated brain endothelial cell death after hypoxia-reoxygenation by disrupting cell-matrix interactions and homeostatic integrin signaling. The cascade of pro-apoptotic events leading to Bax, mitochondria, and caspase-3 activation are regulated by calpastatin and calpain-1. The caspase 3 apoptosis program is not required for anti-inflammatory clearance by human macrophages. The early and temporary activation of PP2A in neutrophils impaired not only the p38 MAPK-mediated inhibition of caspase 3 but also restored the activity to caspase 3 that had already been phosphorylated and thereby inactivated. Translation of some IRES-containing mRNAs is regulated by proteolytic cleavage of PTB during apoptosis.

Pathway TNFRSF6 -> FOXO3A signaling
Apoptosis
intrinsic apoptotic pathway
Trail mediated signaling pathway
FasL mediated signaling pathway
titanium dioxide nanoparticle response pathway

GO Molecular Function hydrolase activity
peptidase activity
cyclin-dependent protein kinase inhibitor activity
phospholipase A2 activator activity
cysteine-type peptidase activity
cysteine-type endopeptidase activity

GO Cellular Component soluble fraction
plasma membrane
cytoplasm
cytosol
mitochondrion
nucleoplasm
nucleolus
nucleus

GO Biological Process hippocampus development
cell fate commitment
heart development
neuron differentiation
keratinocyte differentiation
learning or memory
sensory perception of sound
negative regulation of cell cycle
negative regulation of cyclin-dependent protein kinase activity
negative regulation of phosphorylation
negative regulation of B cell proliferation
negative regulation of activated T cell proliferation
positive regulation of apoptosis
induction of apoptosis
positive regulation of neuron apoptosis
induction of apoptosis by extracellular signals
induction of apoptosis by oxidative stress
induction of apoptosis via death domain receptors
negative regulation of apoptosis
nuclear fragmentation involved in apoptotic nuclear change
DNA fragmentation involved in apoptotic nuclear change
release of cytochrome c from mitochondria
response to DNA damage stimulus
neuron apoptosis
apoptosis
glial cell apoptosis
B cell homeostasis
T cell homeostasis
response to organic substance
response to drug
response to antibiotic
response to hypoxia
response to wounding
response to amino acid stimulus
response to metal ion
response to organic cyclic substance
response to hydrogen peroxide
response to cobalt ion
response to lipopolysaccharide
response to tumor necrosis factor
response to nicotine
response to estradiol stimulus
response to glucocorticoid stimulus
response to glucose stimulus
wound healing
response to X-ray
response to UV
proteolysis
intracellular signaling pathway

Ariadne Ontology CASP3-6-7

Group CASP3-6-7
hippocampus development
cell fate commitment
heart development
neuron differentiation
keratinocyte differentiation
learning or memory
sensory perception of sound
negative regulation of cell cycle
negative regulation of cyclin-dependent protein kinase activity
negative regulation of phosphorylation
negative regulation of B cell proliferation
negative regulation of activated T cell proliferation
positive regulation of apoptosis
induction of apoptosis
positive regulation of neuron apoptosis
induction of apoptosis by extracellular signals
induction of apoptosis by oxidative stress
induction of apoptosis via death domain receptors
negative regulation of apoptosis
nuclear fragmentation involved in apoptotic nuclear change
DNA fragmentation involved in apoptotic nuclear change
release of cytochrome c from mitochondria
response to DNA damage stimulus
neuron apoptosis
apoptosis
glial cell apoptosis
B cell homeostasis
T cell homeostasis
response to organic substance
response to drug
response to antibiotic
response to hypoxia
response to wounding
response to amino acid stimulus
response to metal ion
response to organic cyclic substance
response to hydrogen peroxide
response to cobalt ion
response to lipopolysaccharide
response to tumor necrosis factor
response to nicotine
response to estradiol stimulus
response to glucocorticoid stimulus
response to glucose stimulus
wound healing
response to X-ray
response to UV
proteolysis
intracellular signaling pathway
hydrolase activity
peptidase activity
cyclin-dependent protein kinase inhibitor activity
phospholipase A2 activator activity
cysteine-type peptidase activity
cysteine-type endopeptidase activity
soluble fraction
plasma membrane
cytoplasm
cytosol
mitochondrion
nucleoplasm
nucleolus
nucleus

MedScan ID 836

Hugo ID 1504

Human chromosome position 4q34

LocusLink ID 836
12367
25402

Alias CPP32
SCA-1
CPP32B
caspase-3
Yama
CASP-3
CPP-32
apopain
procaspase3
protein Yama
OTTHUMP00000165053
OTTHUMP00000165055
PARP cleavage protease
cysteine protease CPP32
SREBP cleavage activity 1
caspase 3, apoptosis-related cysteine protease
CC3
Lice
mldy
A830040C14Rik
caspase 3, apoptosis related cysteine protease
MGC93645
IRP
CPP32beta
yama protein
Caspase 3 apoptosis related cysteine protease (ICE-like cysteine protease)
Caspase 3, apoptosis related cysteine protease (ICE-like cysteine protease)
A830040C14
apopains
Casp3
caspase 3
caspase 3, apoptosis-related cysteine peptidase
cysteinease CPP32
devdase
devdases
ICE3
ICE3_HUMAN
ICE-like cysteine protease
Lice protein
OTTHUMP00000165054
Pro-Casp3
procaspase 3
SREBP cleavage activity I
cysteinease CPP32

Organism Homo sapiens
Mus musculus
Rattus norvegicus

GenBank ID NC_000004
NM_032991
NP_116786
NM_004346
NP_004337
NT_016354
NW_922217
NW_001838921
AC_000047
AC_000136
AC073932
AC079257
AY219866
AAO25654
CH471056
EAX04673
EAX04674
EAX04675
EAX04676
CQ786438
CAG17895
AJ413269
CAC88866
AK291337
BAF84026
AU127028
AU133051
BC016926
AAH16926
BU753483
BX647609
CAI46084
CR620420
U13737
AAA65015
U13738
AAB60355
U26943
AAA74929
P42574
Q5HYI3
DQ891543
ABM82469
DQ894731
ABM85657
NC_000074
NM_009810
NP_033940
NT_039460
NW_001030896
AC_000030
AC119267
CH466554
EDL35577
EDL35578
EDL35579
EDL35580
EDL35581
EDL35582
U54801
U54802
AAC52768
U54803
AK014231
AK049043
AK080651
BAC37969
AK146226
BC021500
BC038825
AAH38825
D86352
BAA21727
U19522
AAC53196
U49929
AAC52764
U63720
AAD09504
Y13086
CAA73528
P70677
Q8BNT4
NC_005115
NM_012922
NP_037054
NW_047473
NW_001084718
AC_000084
CH473995
EDL78892
EDL78893
EDL78894
BC081854
AAH81854
U34685
AAC52261
U49930
AAC52765
U84410
AAB41792
P55213
NT_022792
Q9CXM4
XM_991820
NW_000342
XP_996914
BG070529

OMIM ID 600636

Mouse chromosome position 8 26.0 cM

GO ID 0004861
0004197
0008233
0001782
0006309
0043029
0006915
0045165
0007507
0006917
0008624
0008631
0008625
0030216
0030889
0046007
0043066
0045736
0051402
0030264
0006508
0001836
0006974
0009411
0034612
0009611
0007605
0005737
0005829
0005739
0005730
0005654
0005634
0005886
0008234
0016787
0016005
0023034
0007611
0045786
0043065
0043525
0009749
0042542
0005625
0034349
0021766
0042326
0030182
0010165
0043200
0046677
0032025
0042493
0032355
0051384
0001666
0032496
0010038
0035094
0014070
0010033
0042060
0007242
0005515
0030693

Rat chromosome position 16q11

Swiss-Prot Accession P42574
Q5HYI3
P70677
Q8BNT4
P55213
O08668
Q8CHV5
Q9QWI4
P70543
P97699
Q62993
A8K5M2
Q96AN1
Q96KP2
D3DP53

PIR ID JC5410
I67437
A55315

Unigene ID Hs.141125
Mm.34405
Rn.10562

KEGG ID hsa:836
mmu:12367
rno:25402

EC Number 3.4.22.56

Swiss-Prot ID CASP3_MOUSE
CASP3_RAT
CASP3_HUMAN
D3DP53_HUMAN
A8K5M2_HUMAN

Cell Localization Cytoplasm

IPI ID IPI00308498
IPI00215220
IPI00292140
IPI00553172
IPI00798166

Homologene ID 37912

RGD ID 2275

MGI ID 107739

KEGG pathway Huntington's disease
Apoptosis
Natural killer cell mediated cytotoxicity
Alzheimer's disease
Dentatorubropallidoluysian atrophy (DRPLA)
MAPK signaling pathway
Neurodegenerative Disorders