◀ Back to CASP9
CASP3 — CASP9
Pathways - manually collected, often from reviews:
-
BioCarta regulation of cell cycle progression by plk3:
Apaf-1/Caspase 9 complex (APAF1-CASP9)
→
Caspase 3 (CASP3)
(modification, activates)
-
BioCarta regulation of cell cycle progression by plk3:
Apaf-1/Caspase 9 complex (APAF1-CASP9)
→
Caspase 3 (active) (CASP3)
(modification, activates)
-
KEGG p53 signaling pathway:
CASP9
→
CASP3
(protein-protein, activation)
-
KEGG Apoptosis:
CASP9
→
CASP3
(protein-protein, activation)
-
KEGG Alzheimer's disease:
CASP9
→
CASP3
(protein-protein, activation)
-
KEGG Parkinson's disease:
CASP9
→
CASP3
(protein-protein, activation)
-
KEGG Amyotrophic lateral sclerosis (ALS):
CASP9
→
CASP3
(protein-protein, activation)
-
KEGG Huntington's disease:
CASP9
→
CASP3
(protein-protein, activation)
-
KEGG Toxoplasmosis:
CASP9
→
CASP3
(protein-protein, activation)
-
KEGG Tuberculosis:
Complex of APAF1-CASP9-CYCS
→
CASP3
(protein-protein, activation)
-
KEGG Pathways in cancer:
Complex of APPL1-CASP9
→
CASP3
(protein-protein, missing interaction)
-
KEGG Colorectal cancer:
Complex of APPL1-CASP9
→
CASP3
(protein-protein, missing interaction)
-
KEGG Viral myocarditis:
CASP9
→
CASP3
(protein-protein, activation)
-
NCI Pathway Database Caspase Cascade in Apoptosis:
APAF-1/Caspase 9 complex (APAF1-CASP9)
→
Caspase 3 (CASP3)
(modification, activates)
-
NCI Pathway Database HIV-1 Nef: Negative effector of Fas and TNF-alpha:
APAF-1/Caspase 9 complex (APAF1-CASP9)
→
Caspase 3 (CASP3)
(modification, activates)
-
Reactome Reaction:
CASP3
→
CASP9
(reaction)
Zou et al., J Biol Chem 1999*, Liu et al., J Biol Chem 2002*, Arakawa et al., Nat Rev Cancer 2004*, Li et al., Cell 1997*
-
WikiPathways Alzheimers Disease:
CASP9
→
CASP3
(activation)
-
WikiPathways Amyotrophic lateral sclerosis (ALS):
CASP9
→
CASP3
(activation)
-
WikiPathways Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation:
CASP9/APAF1
→
CASP3
(activation)
-
WikiPathways Integrated Breast Cancer Pathway:
CASP9
→
CASP3
(mim-stimulation)
-
WikiPathways Oxidative Damage:
APAF1/CASP9
→
CASP3
(activation)
-
WikiPathways Parkinsons Disease Pathway:
CASP9/CYCS/APAF1
→
CASP6/CASP2/CASP7/CASP3
(mim-stimulation)
-
WikiPathways Apoptosis Modulation by HSP70:
CYCS/APAF1/CASP9
→
CASP3/CASP2/CASP6/CASP7
(activation)
-
WikiPathways miRNA Regulation of DNA Damage Response:
CASP9
→
CASP3
(activation)
Cory et al., Oncogene 2003*, Strasser et al., Nat Rev Immunol 2005
-
WikiPathways Apoptosis:
CASP9
→
CASP3
(activation)
-
WikiPathways Corticotropin-releasing hormone signaling pathway:
CASP9
→
CASP3
(activation)
-
WikiPathways DNA Damage Response:
CASP9
→
CASP3
(activation)
Cory et al., Oncogene 2003*, Strasser et al., Nat Rev Immunol 2005
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
CASP9
—
CASP3
(direct interaction, enzymatic study)
Qiu et al., J Biol Chem 2005
-
IRef Biogrid Interaction:
CASP9
—
CASP3
(direct interaction, enzymatic study)
Denault et al., Biochem J 2007*
-
IRef Biogrid Interaction:
CASP9
—
CASP3
(direct interaction, enzymatic study)
Srinivasula et al., Nature 2001*
-
IRef Biogrid Interaction:
CASP9
—
CASP3
(direct interaction, enzymatic study)
Walsh et al., Proc Natl Acad Sci U S A 2008
-
IRef Dip Interaction:
CASP9
—
CASP3
(direct interaction, protease assay)
Walsh et al., Proc Natl Acad Sci U S A 2008
-
IRef Dip Interaction:
CASP9
—
CASP3
(direct interaction, protease assay)
Chao et al., PLoS Biol 2005*
-
IRef Hprd Interaction:
Complex of 17 proteins
(in vivo)
Bratton et al., EMBO J 2001*
-
IRef Hprd Interaction:
CASP9
—
CASP3
(in vitro)
Kopp et al., Community Dent Oral Epidemiol 1976*, Bratton et al., EMBO J 2001*, Srinivasula et al., J Biol Chem 1996*
-
IRef Innatedb Interaction:
Complex of CASP9-CASP9-XIAP-CASP3-CASP3-XIAP
(unknown, -)
Bratton et al., Cell Death Differ 2002*
-
IRef Innatedb Interaction:
CASP9
—
CASP3
(unknown, -)
Bratton et al., Cell Death Differ 2002*
-
IRef Innatedb Interaction:
CASP9
—
CASP3
(unknown, -)
Denault et al., Biochem J 2007*
-
IRef Innatedb Interaction:
CASP9
—
CASP3
(unknown, -)
Srinivasula et al., J Biol Chem 1996*
-
IRef Innatedb Interaction:
CASP9
—
CASP3
(unknown, -)
Shiozaki et al., Mol Cell 2003*
-
IRef Intact Interaction:
CASP9
—
CASP3
(association, experimental interaction detection)
Bratton et al., EMBO J 2001*
-
IRef Intact Interaction:
Complex of 19 proteins
(direct interaction, protease accessibility laddering)
Yuan et al., Structure 2011*
-
IRef Ophid Interaction:
CASP9
—
CASP3
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
-
IRef Ophid Interaction:
CASP9
—
CASP3
(aggregation, confirmational text mining)
Bratton et al., EMBO J 2001*
Text-mined interactions from Literome
Sun et al., Oncogene 1999
(Adenocarcinoma...) :
The
caspase inhibitors ( Z-DEVD-FMK and Z-VAD-FMK )
suppressed CD437 induced
CPP32-like caspase activation and apoptosis in both cell lines
Selznick et al., J Neuropathol Exp Neurol 2000
:
Caspase-3 deficiency, or pharmacological
inhibition of
caspase activity, prevented caspase-3 activation and blocked the appearance of apoptotic nuclear features but not Abeta induced neuronal death
Nakatsuka et al., Neurosci Lett 2000
(Ischemic Attack, Transient) :
Although
pro-caspase-3 was strongly detected,
active caspase-3 was not
detected before and until 84 h after 5-min ischemia
De Saint Jean et al., Invest Ophthalmol Vis Sci 2000
:
Apoptosis was confirmed by a cleavage of PARP and
CPP32 , by
caspase-8 activation , and by an index Hoechst/neutral red greater than one
Robertson et al., Crit Rev Toxicol 2000
:
Caspase-9 can signal downstream and
activate pro-caspase-3 and -7
Zhang et al., J Neurosci 2000
(Alzheimer Disease) :
Caspase-3 induces neuronal apoptosis in 20 % of the cells, whereas
caspase-7 or -8 do not induce apoptosis
Tomicic et al., Biochem Biophys Res Commun 2001
:
Caspase-3- and caspase-9 mediated cleavage of Bcl-2 was efficiently
blocked by
caspase-3 ( zDEVD ) and caspase-9 ( zLEHD ) inhibitor, respectively
Kagawa et al., Clin Cancer Res 2001
:
Caspase-3 deficiency, however, did not
affect Bax induced levels of poly ( ADP-ribose ) polymerase cleavage,
caspase-6 activation, and lamin B cleavage
Kumi-Diaka et al., Biol Cell 2000
(Carcinoma...) :
The major findings of these studies are : i ) genistein inhibits growth and proliferation of both LNCaP and DU145 cells via apoptosis mainly, and necrosis at higher concentrations ; ii ) genistein induces activation and expression of caspase-3 ( CPP32 ) in both target cells ; iii ) genistein induced apoptosis and
CPP32 activation could be significantly
inhibited by the
caspase-3 inhibitor, z-VAD-fmk ( N-benzyloxycarbonyl-Val-Asp-fluoromethyl-ketone ), thus confirming a mediator role of CPP32 in the genistein induced apoptotic pathway in the target cells
Stadelman et al., Brain Pathol 2001
(Fetal Death...) :
Expression of apoptosis associated proteins p53, bcl-2, bax, and
caspase-3/CPP32 ,
activation of
caspase-3 , and modification of proteins via poly ( ADP-ribosyl ) ation was studied in pontosubicular neuron necrosis ( PSN ), a form of perinatal brain damage revealing the morphological hallmarks of neuronal apoptosis
Viswanath et al., J Neurosci 2001
(Disease Models, Animal...) :
Caspase-9 activation
results in downstream
caspase-8 activation and bid cleavage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson 's disease ...
Caspase-9 inhibition
prevented the activation of both caspase-3 and
caspase-8 and also inhibited Bid cleavage, but not cytochrome c release
Kwon et al., Exp Mol Med 2002
:
Caspase-3 selective inhibitor, Ac-DEVD-CHO,
prevented both the activation of
caspase-3 and cleavage of poly ( ADP-ribose ) polymerase ( PARP )
Robertson et al., Toxicology 2002
(Necrosis) :
Caspase-9 can signal downstream and
activate pro-caspase-3 and -7
Chandra et al., J Biol Chem 2003
:
Here we present evidence that the mitochondrially localized
active caspase-9 and -3 result mostly from translocation from the cytosol ( into the intermembrane space ) and partly from
caspase mediated activation in the organelle rather than from the Apaf-1 mediated activation
Xu et al., Anticancer Res 2003
(Pancreatic Neoplasms) :
Caspase-8 and -3 activities were increased by TRAIL treatment and apoptosis was largely
blocked by
caspase-8 and -3 inhibitors
Schoemaker et al., J Hepatol 2003
(Cholestasis...) :
Apoptosis was determined by TUNEL staining,
active caspase-3 staining,
activation of
caspase-8 , -9 and -3
Aouad et al., J Immunol 2004
:
Caspase-3 is a component of Fas death inducing signaling complex in lipid rafts and its activity is
required for complete
caspase-8 activation during Fas mediated cell death
Cuello et al., Cell Death Differ 2004
:
Caspase-9 may further
activate caspase-8 , generating an amplification loop
Yang et al., Nephron. Experimental nephrology 2004
(Necrosis) :
Here we evaluate three
caspase inhibitors : B-D-FMK ( pan caspase inhibitor ), Z-DEVDFMK ( predominantly Caspase-3 inhibitor ) and Z-VAD-FMK ( predominantly
Caspase-1 and -3 inhibitor ) to ameliorate apoptosis induced by cisplatin in rat proximal tubular ( RPT ) cells
Kusunoki et al., BMC pharmacology 2004
(Arthritis, Rheumatoid) :
Caspase-3 activity was increased by treatment with triptolide and was
suppressed by
caspase inhibitors
Martin et al., J Biol Chem 2005
:
Caspase-9 cleaves and
activates effector caspases, predominantly
caspase-3 , resulting in the demise of the cell
Lang-Rollin et al., Apoptosis 2005
:
Caspase 9 and 3 are processed, cytochrome c is released from the mitochondria and a dominant negative form of
caspase 9
prevents death
Liszewska et al., Prostaglandins Other Lipid Mediat 2005
:
Treatment of luteal cells with P4 and PGE2 for 24 h decreased ( P < 0.05 ) level of
active caspase-3 while aminoglutethimide ( P < 0.05 ), spermine NONOate ( P < 0.05 ), and staurosporine ( P < 0.001 )
increased caspase-3 activity in the cells
Daher et al., Exp Dermatol 2006
:
Caspase-9-DN and zLEHD-fmk both
suppressed caspase-9 , -3, and -8 activity after UVB exposure, as well as proteolytic processing of procaspase-3 into its active form, DNA fragmentation factor 45 cleavage, and internucleosomal DNA fragmentation
Shankar et al., J Neurosci 2006
:
Rhgas6 and
caspase inhibitors also
reduced active caspase-3 immunoreactivity relative to TNFalpha-only treated cultures
Nakadai et al., Toxicology 2006
:
Chlorpyrifos also induced an increase of intracellular
active caspase-3 in U937 cells in a dose dependent manner, and a
caspase-3 inhibitor, Z-DEVD-FMK, significantly
inhibited the chlorpyrifos induced apoptosis
Legewie et al., PLoS Comput Biol 2006
:
We demonstrate that this positive feedback brings about bistability ( i.e., all-or-none behaviour ), and that it cooperates with
Casp3 mediated feedback cleavage of
Casp9 to generate irreversibility in caspase activation
Yang et al., Apoptosis 2006
:
Caspase-3 mediated-feedback and
activation of
caspase-8 and -9 in MCF-7/C3 cells is further supported by an increase in the cleavage of caspase-8 and 9 substrates and cytochrome c release
Koo et al., Am J Chin Med 2007
:
Caspase-3 activation and subsequent apoptotic cell death in MGG treated cells were partially blocked by the
caspase-3 inhibitor, Z-DEVD-FMK
Ikeda et al., Exp Cell Res 2007
:
Caspase-3 activation is also induced, but the
caspase inhibitor, Z-VAD-FMK, does not block RASSF6 mediated apoptosis
Wong et al., Biochim Biophys Acta 2007
:
Caspase-3 is
activated by cleavage of
caspase-8 and caspase-9
Uchiyama et al., Infect Immun 2007
(Necrosis) :
Caspase-9 activation was also detected in H37Rv infected cells, but H37Ra never
induced such
caspase-9 activation
Denault et al., Biochem J 2007
:
Caspase 3 attenuates XIAP ( X-linked inhibitor of apoptosis protein ) -mediated inhibition of
caspase 9
Feng et al., J Huazhong Univ Sci Technolog Med Sci 2007
:
Caspase-3 inhibitors can
suppress caspase-3 activity and reduce the apoptosis rate significantly
Ruiz-Vela et al., FEBS Lett 2007
:
Cytochrome c (CYT c) is a protein that employs the caspase recruitment domain ( CARD ) -containing proteins APAF-1 and
CASP-9 to
activate effectors
CASP-3 and -7
Li et al., Toxicology 2007
:
DDVP also induced an increase of intracellular
active caspase-3 in NK-92CI in a dose- and time dependent manner, and a
caspase-3 inhibitor, Z-DEVD-FMK, significantly
inhibited DDVP induced apoptosis, suggesting that this apoptosis is partially mediated by activation of intracellular caspase-3
Wei et al., Zhonghua Xue Ye Xue Za Zhi 2007
:
The
caspase-3 activity was markedly enhanced, and the
active caspase-3 in K562/ADM cells
increased by about 40 % compared to liposome alone and non silencing controls
Audo et al., Arthritis Res Ther 2007
(Arthritis, Rheumatoid) :
Caspase 3 , a key mediator of apoptosis, was not activated in celecoxib treated RA FLSs, and the presence of specific
caspase 3 or pan-caspase inhibitors did not
affect celecoxib induced cell death
Scarlatti et al., Cell Death Differ 2008
(Breast Neoplasms) :
Here we show that resveratrol arrests cell proliferation, triggers death and decreases the number of colonies of cells that are sensitive to
caspase-3 dependent apoptosis ( MCF-7
casp-3 ) and also those that are unresponsive to it ( MCF-7vc )
Li et al., Toxicology 2009
:
Chlorpyrifos also induced an increase in intracellular
active caspase-3 in Jurkat T cells in a dose- and time dependent manner, and a
caspase-3 inhibitor, Z-DEVD-FMK, significantly
inhibited chlorpyrifos induced apoptosis
Zhao et al., Tohoku J Exp Med 2008
(Myocardial Infarction...) :
Caspase-9 cleaves and
activates caspase-3
Liang et al., Zhonghua Yu Fang Yi Xue Za Zhi 2008
:
p, p'-DDE, beta-BHC and their mixture could induce the apoptosis of Sertoli cells in vitro which was associated with activation of
Caspase-3 mediated by cleavage of Caspase-8 and
Caspase-9
Tang et al., Oncol Rep 2009
(Adenocarcinoma...) :
Caspase-9 and -3 inhibitors almost completely
suppressed HCT induced
caspase-9 and -3 activities ...
Caspase-9 and -3 inhibitors almost completely
suppressed HCT induced
caspase-9 and -3 activities
Shi et al., Toxicol Lett 2010
:
Caspase 9 inhibition
blocked the TNP induced activation of
caspase 3 significantly
Ohsawa et al., Proc Natl Acad Sci U S A 2010
:
Maturation of the olfactory sensory neurons by
Apaf-1/caspase-9 mediated
caspase activity ... Here, we provide unique evidence that
Apaf-1/caspase-9 mediated
caspase signaling regulates the development of olfactory sensory neurons ( OSNs ), which includes axonal projection, synapse formation, and maturation of these neurons
Li et al., Arch Toxicol 2011
(Necrosis) :
DNA fragmentation was detected when cells were treated with 0.5, 1, or 2 µM ziram for 24 h. Ziram also induced an increase in intracellular
active caspase-3 in U937 cells in a dose dependent manner, and a
caspase-3 inhibitor, Z-DEVD-FMK, significantly
inhibited the ziram induced apoptosis
Xiao et al., Apoptosis 2011
:
Caspase-3 activity was 10-fold higher in myotubes compared to myoblasts, and Stsp
caused a significant
caspase-3 induction in both
Jeyasuria et al., Biol Reprod 2011
:
The IAP family members are the only endogenous inhibitors of
active caspase 3 , and MCL1 limits
activation of
caspase 3 by suppressing proapoptotic signaling
Aras et al., Brain Res 2012
(Gliosis) :
Reactive neonatal and adult astrocytes demonstrated an
increase in total
caspase activity with a corresponding increase in the expression of
active caspase-3 in the absence of cell death
Edgington et al., Chem Biol 2012
:
We also demonstrate that
caspase-6 activation does not
require active caspase-3/-7 , suggesting that it may autoactivate or be cleaved by other proteases
Nelson et al., Crit Care Med 2012
(Muscular Atrophy) :
These findings support our hypothesis that a regulatory calpain/caspase-3 cross-talk exists whereby calpain can promote
caspase-3 activation and
active caspase-3 can
enhance calpain activity in diaphragm muscle during prolonged mechanical ventilation
Wang et al., PloS one 2012
:
Caspase assay demonstrated that Caspase-3, -8, -9 enzyme activities in newt testis were significantly elevated after heat shock ( 40°C 2 h ), cold exposure ( 4°C 12 h ), and cadmium exposure ( Cd 36 h ), while
Caspase3 and Caspase8 activities were
increased with
Caspase9 significantly decreased after starvation treatment
Chan et al., J Virol 2012
:
However, HCMV infection does
induce a temporal activation of
caspase 3, with only a low level of
active caspase 3 being observed after the 48-h viability checkpoint
Liu et al., PloS one 2012
:
Caspase-9 inhibitor could
inhibit activation of
pro-caspase-3 , and the inhibition of the function of Apaf-1 with FSBA blocked apoptosis, hinting that Apaf-1 could be involved in Sl-1 cell apoptosis induced by AfMNPV
Jiang et al., Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 2013
:
Subchronic exposure to B [ a ] P can induce apoptosis of hippocampal neurons ; its mechanism may be related to the fact that B [ a ] P can induce upregulated expression of Bax, inhibit expression of Bcl-2, lead to decrease in Bcl-2/Bax ratio,
induce upregulated expression of
Caspase-3 and Caspase-6, and cause increase in the activities of Caspase-3, Caspase-6, and
Caspase-9
Wu et al., Food Chem Toxicol 2013
:
Caspase-3 inhibitor also efficiently
blocked CD95 ( APO-1/CD95 ) and Bax expression,
caspase-3 activation and PARP cleavage, whereas antioxidant N-acetyl-l-cysteine, AMPK inhibitor and AMPK siRNA effectively blocked the AMPK phosphorylation
Wright et al., J Exp Med 1997
(Lymphoma) :
Only the
caspase inhibitors, however,
prevented activation of
CPP32-like activity as revealed by cleavage of the synthetic substrate, DEVD-pNa, by cell cytosols, and also by in vivo cleavage of poly ( ADP-ribosyl ) polymerase, a known substrate of CPP32
Deveraux et al., EMBO J 1998
:
In contrast, these IAP family proteins did not
prevent caspase-8 induced proteolytic activation of
pro-caspase-3 ; however, they subsequently inhibited
active caspase-3 directly, thus blocking downstream apoptotic events such as further activation of caspases
Cecconi et al., Cell 1998
(Craniofacial Abnormalities...) :
The cytosolic protein APAF1, human homolog of C. elegans CED-4, participates in the
CASPASE 9 (CASP9) dependent activation of
CASP3 in the general apoptotic pathway