◀ Back to CASP3
CASP3 — CASP8
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
CASP3
→
CASP8
(increases, CASP8 Activity)
Evidence: the classical induction of AICD is mediated via CD95, ligation of CD95 by CD95L leads to the recruitment of adapter proteins such as FADD, resulting in the activation of caspase 8, which in turn activates downstream caspases, including caspase 3, 6 and 7, and initates apoptosis independently of the apoptosome, although cytochrome C release and apoptosome activation are required for efficient cell death
-
OpenBEL Selventa BEL large corpus:
CASP3
→
CASP8
(directlyIncreases, CASP8 Activity, CASP3 Activity)
Evidence: when initiator caspases, such as caspase-8 and caspase-9, are activated by oligomerization, they cleave the precursor forms of effector caspases, such as caspase-3, caspase-6 and caspase-7
-
OpenBEL Selventa BEL large corpus:
CASP3
→
CASP8
(directlyIncreases, CASP8 Activity, CASP3 Activity)
Evidence: The death effector domain (DED) of FADD then binds to the DED of procaspase 8, which triggers the formation of activated caspase 8, the activation of caspase 3, and the apoptotic response.
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
Caspase 3 (CASP3)
→
DR4/5/Caspase 8/Caspase 10/APO-2L complex (TNFRSF10B_TNFRSF10A-CASP8-CASP10-TNFSF10)
(modification, collaborate)
-
BioCarta caspase cascade in apoptosis:
Caspase 8 (active) (CASP8)
→
Caspase 3 (CASP3)
(modification, activates)
-
BioCarta caspase cascade in apoptosis:
Caspase 8 (active) (CASP8)
→
Caspase 3 (active) (CASP3)
(modification, activates)
-
BioCarta hiv-1 nef: negative effector of fas and tnf:
Caspase 3 (CASP3)
→
Caspase 8/Caspase 8/Caspase 8/Caspase 8 complex (CASP8)
(modification, collaborate)
-
BioCarta hiv-1 nef: negative effector of fas and tnf:
Caspase 8/Caspase 8/Caspase 8/Caspase 8 complex (CASP8)
→
Caspase 3 (active) (CASP3)
(modification, activates)
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10/APO-3L complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10-TNFSF12)
→
Caspase 3 (CASP3)
(modification, activates)
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10/APO-3L complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10-TNFSF12)
→
Caspase 3 (active) (CASP3)
(modification, activates)
-
BioCarta tnfr1 signaling pathway:
Caspase 8 (CASP8)
→
Caspase 3 (CASP3)
(modification, activates)
-
BioCarta tnfr1 signaling pathway:
Caspase 8 (CASP8)
→
Caspase 3 (active) (CASP3)
(modification, activates)
-
KEGG p53 signaling pathway:
CASP8
→
CASP3
(protein-protein, activation)
-
KEGG Apoptosis:
CASP8
→
CASP3
(protein-protein, activation)
-
KEGG Huntington's disease:
CASP8
→
CASP3
(protein-protein, activation)
-
KEGG Toxoplasmosis:
CASP8
→
CASP3
(protein-protein, activation)
-
KEGG Tuberculosis:
CASP8
→
CASP3
(protein-protein, activation)
-
NCI Pathway Database Caspase Cascade in Apoptosis:
Caspase 8 (CASP8)
→
Caspase 3 (CASP3)
(modification, activates)
-
NCI Pathway Database FAS (CD95) signaling pathway:
Caspase 8 (tetramer)/FADD/FADD complex (CASP8-FADD)
→
Caspase 3 (CASP3)
(modification, activates)
Stennicke et al., J Biol Chem 1998*
Evidence: mutant phenotype, assay
-
NCI Pathway Database FAS (CD95) signaling pathway:
Caspase 8 (tetramer)/FADD/FADD complex (CASP8-FADD)
→
Caspase 3 (tetramer) complex (CASP3)
(modification, activates)
Stennicke et al., J Biol Chem 1998*
Evidence: mutant phenotype, assay
-
WikiPathways Alzheimers Disease:
CASP8
→
CASP3
(activation)
-
WikiPathways Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation:
CASP8
→
CASP3
(activation)
-
WikiPathways Integrated Breast Cancer Pathway:
CASP8
→
CASP3
(mim-stimulation)
-
WikiPathways Nanomaterial induced apoptosis:
CASP8
→
CASP7/CASP6/CASP3
(activation)
-
WikiPathways miRNA Regulation of DNA Damage Response:
CASP8
→
CASP3
(activation)
Strasser et al., Nat Rev Immunol 2005
-
WikiPathways Apoptosis:
CASP8
→
CASP3
(activation)
-
WikiPathways DNA Damage Response:
CASP8
→
CASP3
(activation)
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 Bind Interaction:
CASP8
—
CASP3
Becker et al., J Med Chem 2004*
-
IRef Bind_translation Interaction:
CASP8
—
CASP3
(x-ray crystallography)
Becker et al., J Med Chem 2004*
-
IRef Bind_translation Interaction:
CASP8
—
CASP3
(x-ray crystallography)
Becker et al., J Med Chem 2004*
-
IRef Biogrid Interaction:
CASP3
—
CASP8
(direct interaction, enzymatic study)
Chandra et al., Mol Cell Biol 2004*
-
IRef Biogrid Interaction:
CASP3
—
CASP8
(direct interaction, enzymatic study)
Guo et al., J Biol Chem 2002
-
IRef Biogrid Interaction:
CASP3
—
CASP8
(direct interaction, enzymatic study)
Srinivasula et al., Proc Natl Acad Sci U S A 1996
-
IRef Dip Interaction:
CASP8
—
CASP3
(direct interaction, protease assay)
Stegh et al., Proc Natl Acad Sci U S A 2008*
-
IRef Hprd Interaction:
CASP8
—
CASP3
(in vivo)
Rank et al., Protein Expr Purif 2001*
-
IRef Hprd Interaction:
CASP8
—
CASP3
(in vitro)
Rank et al., Protein Expr Purif 2001*
-
IRef Innatedb Interaction:
Complex of CASP8-CASP3-CFLAR
(unknown, -)
Shu et al., Immunity 1997*
-
IRef Innatedb Interaction:
CASP8
—
CASP3
(unknown, -)
Scott et al., J Biol Chem 2008*
-
IRef Innatedb Interaction:
CASP8
—
CASP3
(unknown, -)
Casciola-Rosen et al., J Biol Chem 2007*
-
IRef Innatedb Interaction:
CASP8
—
CASP3
(unknown, -)
Han et al., J Biol Chem 2004*
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
Zhuang et al., Exp Cell Res 1999
:
Caspase-8 mediates
caspase-3 activation and cytochrome c release during singlet oxygen induced apoptosis of HL-60 cells
Raoul et al., J Cell Biol 1999
:
Motoneurons resistant to Fas activation expressed high levels of
FLICE-inhibitory protein (FLIP) , an endogenous
inhibitor of
caspase-8 activation
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
Okamoto et al., Rheumatology (Oxford) 2000
(Arthritis, Rheumatoid) :
Caspase-8-specific inhibitor
suppressed the activation of
caspase-3 after Fas ligation on RA synoviocytes
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
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
Hernandez et al., Surgery 2001
(Colonic Neoplasms) :
Western blots were performed to assess intracellular expression of
Flice-like inhibitory protein (FLIP) , a
caspase inhibitor
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 )
Thomas et al., Surgery 2002
(Pancreatic Neoplasms) :
FLICE-like inhibitory protein (FLIP) , an
inhibitor of
caspase-8 , ( also known as FLICE ) is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB) and can contribute to TRAIL resistance
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 ...
Caspase-8 and -3 activities were increased by TRAIL treatment and apoptosis was largely
blocked by
caspase-8 and -3 inhibitors
Fujii et al., Infect Immun 2003
:
Caspase-8 is known to activate Bid, and a specific inhibitor of
caspase-8 prevented the mitochondrial damage
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
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
Perchellet et al., Anticancer Drugs 2004
:
Caspase-2 and -8 may both act upstream of mitochondria to promote Cyt c release, but
caspase-2 is already maximally
activated 6 h after 4 microM DAU or TT13 treatments, whereas DAU- or TT-induced caspase-8 and -9 activities peak at 9 h. Pre-treatments with 15 microM of the caspase-2 inhibitor benzyloxycarbonyl ( z ) -Val-Asp-Val-Ala-Asp ( VDVAD ) -fluoromethyl ketone ( fmk ) totally block DAU- and TT13 induced caspase-2, -8 and -9 activities, whereas pre-treatments with 15 microM of the caspase-8 inhibitor z-Ile-Glu-Thr-Asp ( IETD ) -fmk prevent DAU and TT13 from inducing caspase-8 activities without affecting their caspase-2- and -9-inducing activities, suggesting that the induction of apical caspase-2 activity by these drugs may be a critical upstream event required for the activation of other downstream caspases, including caspase-9 and the mitochondrial amplification loop through caspase-8
Maitra et al., Crit Care Med 2005
(Sepsis) :
Caspase-8 activates
caspase-3 , which in turn degrades fibronectin and focal adhesion kinase and leads to disruption of hepatic architecture and integrity
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
Miyao et al., Otol Neurotol 2006
(Cholesteatoma, Middle Ear) :
Caspase-8 , which is activated by the induction of tumor necrosis factor-alpha,
leads to activation of
caspase-3 , which activates apoptotic nucleases
Wu et al., Cell Mol Life Sci 2006
:
Caspase-8 played important roles in the activation of
caspase-3 and induction of apoptosis, whereas the role of the caspase-9 was limited
Shankar et al., J Neurosci 2006
:
Rhgas6 and
caspase inhibitors also
reduced active caspase-3 immunoreactivity relative to TNFalpha-only treated cultures
Yamaguchi et al., Biochim Biophys Acta 2006
(Carcinoma, Hepatocellular...) :
We demonstrated that
Adv-Casp8 increased expression of active forms of
caspase-8 in MOI dependent manner
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
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
Faragher et al., Mol Biol Cell 2007
(Breast Neoplasms) :
Caspase-8 activates cytoplasmic
caspase-7 , which is likely to be the primary caspase responsible for cleavage of CENP-C and INCENP, a key chromosomal passenger protein
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
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
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
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
Pesakhov et al., Nutr Cancer 2010
(Leukemia, Myeloid, Acute) :
Caspase-8 inhibition abrogated Bid cleavage and strongly
reduced caspase-9 activation, suggesting that the cross-talk mechanism mediated by caspase-8 dependent Bid cleavage can contribute to the activation of the intrinsic apoptotic pathway by curcumin + carnosic acid
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
Moujalled et al., Cell Death Differ 2012
:
In mouse embryonic fibroblasts, neither caspase-8 nor cellular
FLICE-inhibitory protein (FLIP) is necessary for TNF to activate NF-?B, but
caspase-8 is
required for TNF to cause cell death, and induction of FLIP by NF-?B is required to prevent it
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
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
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
Sata et al., J Biol Chem 1998
:
Here, we show that endothelial cell apoptosis by OxLDL and LPC-C16 : 0 was dose dependent and correlated with down-regulation of
FLICE-inhibitory protein (FLIP) , an intracellular
caspase inhibitor
Yamashita et al., Blood 1999
:
Caspase-8 activated
caspase-3 and T18 in neutrophil cytoplasmic extracts