◀ Back to CASP3
CASP3 — XIAP
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
CASP3
→
XIAP
(directlyDecreases, XIAP Activity)
Evidence: Table 1 Apparent inhibitory constants (KI,app in M) for IAPs against selected human caspases
-
OpenBEL Selventa BEL large corpus:
CASP3
→
XIAP
(directlyDecreases, XIAP Activity)
Evidence: XIAP, c-IAP1 and c-IAP2 are thought to directly inhibit certain caspases (caspase-3, caspase-7 and caspase-9; TABLE 1).
-
KEGG Apoptosis:
BIRC2/BIRC3/XIAP
→
CASP3
(protein-protein, inhibition)
-
KEGG Toxoplasmosis:
BIRC2/BIRC3/XIAP
→
CASP3
(protein-protein, inhibition)
-
NCI Pathway Database Caspase Cascade in Apoptosis:
XIAP (XIAP)
→
Caspase 3 (CASP3)
(modification, inhibits)
-
NCI Pathway Database Caspase Cascade in Apoptosis:
XIAP (XIAP)
→
Caspase 3 (CASP3)
(modification, inhibits)
Quan et al., Proc Natl Acad Sci U S A 1996*
Evidence: assay
-
NCI Pathway Database Caspase Cascade in Apoptosis:
XIAP (XIAP)
→
Caspase 3 (CASP3)
(modification, inhibits)
-
NCI Pathway Database Caspase Cascade in Apoptosis:
XIAP (XIAP)
→
Caspase 3 (CASP3)
(modification, inhibits)
-
NCI Pathway Database Caspase Cascade in Apoptosis:
XIAP (XIAP)
→
Caspase 3 (CASP3)
(modification, inhibits)
-
Reactome Reaction:
XIAP
→
CASP3
(indirect_complex)
-
Reactome Reaction:
XIAP
→
CASP3
(reaction)
Kashkar et al., J Exp Med 2003*
-
WikiPathways Copper homeostasis:
XIAP
→
CASP3
(inhibition)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Bind Interaction:
XIAP
—
CASP3
Scott et al., EMBO J 2005*
-
IRef Bind Interaction:
XIAP
—
CASP3
Riedl et al., Cell 2001*
-
IRef Bind Interaction:
XIAP
—
CASP3
Bartke et al., Mol Cell 2004
-
IRef Bind_translation Interaction:
XIAP
—
CASP3
(x-ray crystallography)
Riedl et al., Cell 2001*
-
IRef Bind_translation Interaction:
XIAP
—
CASP3
(experimental interaction detection)
Scott et al., EMBO J 2005*
-
IRef Bind_translation Interaction:
XIAP
—
CASP3
(coimmunoprecipitation)
Bartke et al., Mol Cell 2004
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Nomura et al., Urol Res 2003*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Paulsen et al., Eur J Immunol 2008*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(association, x-ray crystallography)
Scott et al., EMBO J 2005*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Mufti et al., Mol Cell 2006*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Rajalingam et al., PLoS Pathog 2006*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Dudich et al., FEBS J 2006*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Chai et al., Cell 2001*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Checinska et al., Exp Cell Res 2007*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Sun et al., Cell Signal 2009*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Takahashi et al., J Biol Chem 1998*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Condé et al., PloS one 2012*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, enzymatic study)
Walsh et al., Proc Natl Acad Sci U S A 2008
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Suzuki et al., Proc Natl Acad Sci U S A 2001*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Suzuki et al., Proc Natl Acad Sci U S A 2001*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Silke et al., J Cell Biol 2002*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(association, x-ray crystallography)
Riedl et al., Cell 2001*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Riedl et al., Cell 2001*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Roy et al., EMBO J 1997
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Deveraux et al., Nature 1997*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Suzuki et al., J Biol Chem 2001*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Bartke et al., Mol Cell 2004
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(physical association, affinity chromatography technology)
Nakhaei et al., J Virol 2012*
-
IRef Biogrid Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Qiu et al., J Biol Chem 2005
-
IRef Hprd Interaction:
Complex of 17 proteins
(in vivo)
Bratton et al., EMBO J 2001*
-
IRef Hprd Interaction:
XIAP
—
CASP3
(in vivo)
Suzuki et al., Proc Natl Acad Sci U S A 2001*, Silke et al., J Cell Biol 2002*, Deveraux et al., Nature 1997*, Takahashi et al., J Biol Chem 1998*
-
IRef Hprd Interaction:
XIAP
—
CASP3
(in vitro)
Suzuki et al., Proc Natl Acad Sci U S A 2001*, Silke et al., J Cell Biol 2002*, Deveraux et al., Nature 1997*, Takahashi et al., J Biol Chem 1998*
-
IRef Innatedb Interaction:
Complex of CASP9-CASP9-XIAP-CASP3-CASP3-XIAP
(unknown, -)
Bratton et al., Cell Death Differ 2002*
-
IRef Innatedb Interaction:
Complex of XIAP-APAF1-CASP3
(unknown, -)
Kashkar et al., J Exp Med 2003*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Rajalingam et al., PLoS Pathog 2006*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Han et al., J Biol Chem 2004*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Deveraux et al., EMBO J 1998*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Bratton et al., EMBO J 2001*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Silke et al., J Cell Biol 2002*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Takahashi et al., J Biol Chem 1998*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Deveraux et al., Nature 1997*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Suzuki et al., Proc Natl Acad Sci U S A 2001*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Suzuki et al., J Biol Chem 2001*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Bartke et al., Mol Cell 2004
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Bratton et al., Cell Death Differ 2002*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Ekert et al., J Cell Biol 2001*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Riedl et al., Cell 2001*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Lüthi et al., Immunity 2009*
-
IRef Innatedb Interaction:
XIAP
—
CASP3
(unknown, -)
Leverkus et al., Mol Cell Biol 2003*
-
IRef Intact Interaction:
Complex of CASP3-XIAP-CASP3
(physical association, x-ray crystallography)
Riedl et al., Cell 2001*
-
IRef Intact Interaction:
XIAP
—
CASP3
(direct interaction, pull down)
Takahashi et al., J Biol Chem 1998*
-
IRef Ophid Interaction:
XIAP
—
CASP3
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Perkins et al., Cancer Res 2000
:
This conclusion is supported by the observation that in HL-60/Apaf-1 cells, ectopic expression of dominant negative caspase-9, its inhibitory short isoform caspase-9b, or
XIAP or treatment with the caspase inhibitor zVAD ( 50 microM )
inhibited Apaf-1 induced
caspase-8 and Bid cleavage, mitochondrial deltapsim, release of cyt c, and apoptosis
Johnson et al., Cancer Res 2000
:
The cleavage of
hILP appears to be
caspase mediated because the production of the p29 protein was inhibited by the pan-caspase peptide inhibitor, Z-VAD.FMK
Sasaki et al., Cancer Res 2000
(Adenocarcinoma...) :
Xiap down-regulation
resulted in
caspase-3 activation, caspase mediated MDM2 processing, and p53 accumulation
Liston et al., Nat Cell Biol 2001
:
XIAP suppresses
caspase activation and cell death in vitro, and XAF1 antagonizes these XIAP activities
Korhonen et al., Mol Cell Neurosci 2001
(Nerve Degeneration) :
The results show that there is biphasic regulation of XIAP in the hippocampus following kainic acid and that
XIAP becomes a
target for
caspase-3 activated during cell death in the hippocampus
Bratton et al., EMBO J 2001
:
Thus,
XIAP may
regulate cell death by inhibiting the activation of
caspase-3 within the apoptosome and by preventing release of active caspase-3 from the complex
Suzuki et al., Proc Natl Acad Sci U S A 2001
:
Ubiquitin-protein ligase activity of
X-linked inhibitor of apoptosis protein promotes proteasomal degradation of
caspase-3 and enhances its anti-apoptotic effect in Fas induced cell death ... In this study, using constitutively active mutants of caspase-3, we found that
XIAP promotes the degradation of active-form
caspase-3 , but not procaspase-3, in living cells ... These results demonstrate that the ubiquitin-protein ligase activity of
XIAP promotes the degradation of
caspase-3 , which enhances its anti-apoptotic effect
Kwon et al., Biochem Biophys Res Commun 2001
:
Moreover, PMA ( phorbol myristate acetate ), PKC ( protein kinase C ) activator, protected U937 cells from okadaic acid induced apoptosis, abrogated okadaic acid induced
caspase 3 activation, and specifically
inhibited downregulation of
XIAP ( X-linked inhibitor of apoptosis ) by okadaic acid
Partheniou et al., Biochem Biophys Res Commun 2001
(Leukemia) :
In contrast, there was a
caspase dependent cleavage of
XIAP , but not c-IAP1, during treatment with TNFalpha for 7 days
Verhagen et al., J Biol Chem 2002
:
HtrA2 can, like DIABLO/Smac, prevent
XIAP inhibition of
active caspase 3 in vitro and is able to counteract XIAP protection of mammalian NT2 cells against UV-induced cell death
Lin et al., Exp Cell Res 2002
(MAP Kinase Signaling System) :
Apoptosis resistance was associated with an enhanced expression of
X-linked inhibitor of apoptosis protein ( XIAP ), an endogenous
caspase inhibitor , in differentiated THP-1 cells
van Loo et al., Cell Death Differ 2002
(Translocation, Genetic) :
Omi interacts with caspase-inhibitor
XIAP and
induces enhanced
caspase activity
Sanna et al., Mol Cell Biol 2002
:
Importantly, expression of catalytically inactive TAK1 did not affect
XIAP inhibition of
caspase activity
Sasaki et al., Gynecol Oncol 2002
(Neoplastic Cells, Circulating...) :
Overexpression of
X-linked inhibitor of apoptosis protein ( Xiap ), an endogenous
caspase inhibitor , attenuated the cisplatin induced FAK processing, morphologic changes, and apoptosis
Sanna et al., J Biol Chem 2002
:
Finally, expression of ILPIP did not affect the ability of
XIAP to
inhibit caspase activation, further supporting the idea that XIAP protection against apoptosis is achieved by two separate mechanisms : one requiring JNK1 activation and a second involving caspase inhibition
Ishigaki et al., J Neurochem 2002
(Amyotrophic Lateral Sclerosis...) :
Overexpression of
XIAP markedly
inhibited the cell death and
caspase-3 activity in the neuro2a cells expressing mutant SOD1
Bratton et al., Cell Death Differ 2002
:
XIAP inhibition of
caspase-3 preserves its association with the Apaf-1 apoptosome and prevents CD95- and Bax induced apoptosis
Hwang et al., Int J Oncol 2003
:
Taken together, the apoptotic effects of NPPA may be related, in part to the caspase-3 activation, the down-regulation of
XIAP , and Bax cleavage
mediated by
caspase dependent calpain activation
Tamm et al., J Biol Chem 2003
:
Protein-protein interaction assays revealed that
caspase-3 and caspase-7 ( but not caspase-8 )
blocked the binding of the CEFESC phage to
XIAP , indicating that this peptide targets a domain within XIAP that is related to the caspase binding site
Shiozaki et al., Mol Cell 2003
:
Mechanism of
XIAP mediated inhibition of
caspase-9
Nomura et al., Urol Res 2003
(Prostatic Neoplasms) :
The
effects of
XIAP overexpression on
caspase-3 were examined by immunoblot analysis and activity assay ... In addition, we found that taxol treatment induced the cleavage of
pro-caspase-3 , followed by apoptosis, and that the overexpression of
XIAP inhibited apoptosis by attenuating the cleavage of pro-caspase-3 and caspase-3 activity
Kashkar et al., J Exp Med 2003
(Hodgkin Disease) :
XIAP mediated
caspase inhibition in Hodgkin 's lymphoma derived B cells ... Even after stimulation with exogenous cytochrome c and dATP,
XIAP impairs the proteolytic processing and activation of
caspase-3
Saito et al., J Cereb Blood Flow Metab 2003
(Ischemic Attack, Transient) :
XIAP increased concurrently with the release of Smac/DIABLO and the appearance of activated
caspase-9 during the early period after reperfusion injury ... Neither
XIAP nor Smac/DIABLO expression was
affected by
caspase inhibition
Huang et al., J Biol Chem 2003
:
A mitochondrial protein Smac/DIABLO, which is released during apoptosis, antagonizes
XIAP mediated
caspase inhibition by interacting directly with XIAP ... This 2 : 1 Smac/XIAP interaction not only possesses enhanced affinity but also sterically excludes XIAP/caspase-7 interaction, demonstrating the requirement of both BIR2 and BIR3 domains for Smac to relieve
XIAP mediated
caspase inhibition
Pardo et al., Mol Cell Biol 2003
(Carcinoma, Small Cell) :
Exogenous expression of
XIAP is
sufficient to inhibit
caspase 9 activation, Smac release, and cell death induced by etoposide
Straszewski-Chavez et al., Mol Hum Reprod 2004
:
As a potent caspase inhibitor,
XIAP prevents the activation of
caspase-9 through its BIR3 domain and caspase-3 activation via the linker-BIR2 domain
Kim et al., Br J Haematol 2004
(Leukemia, Myelogenous, Chronic, BCR-ABL Positive) :
In summary, these data indicate that apicidin potentiates the imatinib induced apoptosis of Bcr-Abl positive leukaemia cells through the enhanced activation of the mitochondria dependent caspase cascades, accompanied by
caspase dependent downregulation of Bcr-Abl and
XIAP
Kim et al., Oncogene 2004
(Glioma) :
We found that treatment with roscovitine or expression of a dominant negative Cdc2 mutant downregulated the protein levels of survivin and
XIAP , two major
caspase inhibitors
Dirks et al., Free Radic Biol Med 2004
(Body Weight) :
Neither age nor calorie restriction had any effect on muscle caspase-3 enzyme activity, but the levels of
X-linked inhibitor of apoptosis , particularly an
inhibitor of
caspase-3 , increased with age and were reduced significantly in the 26 month old calorie restricted cohort
Huang et al., Cancer Cell 2004
:
Antagonizing
XIAP mediated
caspase-3 inhibition ... In comparison with Smac peptides targeting
XIAP mediated
caspase-9 inhibition, which do not directly induce cell death, it appears that liberating downstream caspases rather than upstream caspases may be a preferred strategy for cancer drug discovery
Schimmer et al., Cancer Cell 2004
(Neoplasms, Experimental) :
We developed an enzyme derepression assay, based on overcoming
XIAP mediated suppression of
Caspase-3 , and screened mixture based combinatorial chemical libraries for compounds that reversed XIAP mediated inhibition of Caspase-3, identifying a class of polyphenylureas with XIAP-inhibitory activity
Mühlethaler-Mottet et al., Oncogene 2004
(Neuroblastoma) :
Drug mediated sensitization to TRAIL induced apoptosis in caspase-8 complemented neuroblastoma cells proceeds via activation of intrinsic and extrinsic pathways and
caspase dependent cleavage of
XIAP , Bcl-xL and RIP
Hentze et al., Hepatology 2004
:
CPT treatment completely abrogated the TNF induced NF-kappa B activation, and mRNA expression of the antiapoptotic factors TNF-receptor associated factor 2, FLICE-inhibitory protein, and
X-linked inhibitor of apoptosis protein was also
inhibited by CPT. The
caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp- ( OMe ) -fluoromethylketone ( zVAD-fmk ) and benzyloxycarbonyl-Asp ( OMe ) -Glu ( OMe ) -Val-Asp ( OMe ) -chloromethylketone ( zDEVD-fmk ), as well as depletion of intracellular ATP by fructose prevented CPT/TNF induced apoptosis
Amantana et al., Mol Cancer Ther 2004
(Prostatic Neoplasms) :
Specific inhibition of
XIAP expression using an antisense XIAP phosphorodiamidate morpholino oligomer induced apoptosis and
increased caspase-3 activity
Johnson et al., Exp Cell Res 2004
(Carcinoma...) :
Overexpression of
XIAP restored active caspase 3 ubiquitination and lowered levels of
caspase 3 activity
Wilkinson et al., Mol Cell Biol 2004
:
These data demonstrate for the first time that full-length
XIAP inhibits
caspase activation required for mitochondrial amplification of death receptor signals and that, by acting upstream of mitochondrial activation, XIAP supports the long-term proliferative capacity of cells following CD95 stimulation
Rosato et al., Leukemia 2004
(Leukemia...) :
Moreover, cells stably expressing an XIAP-antisense construct exhibited a pronounced increase in TRAIL sensitivity comparable to degrees of apoptosis achieved with TRAIL/FP. Conversely, enforced
XIAP expression significantly
attenuated caspase activation and TRAIL/FP lethality
Naumann et al., Cell Death Differ 2004
(Brain Neoplasms...) :
Adenoviral
X-linked inhibitor of apoptosis (XIAP) gene transfer, or exposure to the caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoro-methylketone zVAD-fmk,
blocks caspase-7 and PARP processing, but not cell death, whereas BCL-X ( L ) blocks not only caspase-7 and PARP processing but also cell death
Xu et al., J Clin Endocrinol Metab 2004
(Ovarian Neoplasms) :
These findings demonstrate that Nodal induces apoptosis and inhibits proliferation via ALK7 and Smad2/3 and that the effect of Nodal-ALK7 on apoptosis may be mediated in part by the down-regulation of
Xiap and
activation of
caspase-9 and caspase-3
Kim et al., Oncogene 2005
(Glioma) :
Furthermore, treatment with rottlerin downregulated the protein levels of survivin and
X-chromosome linked IAP (XIAP) , two major
caspase inhibitors
Liu et al., Circulation 2005
(Myocardial Infarction...) :
Furthermore, treatment with ucf-101 before reperfusion attenuated
X-linked inhibitor of apoptosis protein degradation and
inhibited caspase-9 and caspase-3 activities
Ma et al., Blood 2005
(Multiple Myeloma) :
Baicalein inhibited the phosphorylation of IkB-alpha, which was followed by decreased expression of the IL-6 and
XIAP genes and
activation of
caspase-9 and caspase-3
Scott et al., EMBO J 2005
:
XIAP inhibits
caspase-3 and -7 using two binding sites : evolutionarily conserved mechanism of IAPs ... The
X-linked inhibitor of apoptosis protein ( XIAP ) uses its second baculovirus IAP repeat domain ( BIR2 ) to
inhibit the apoptotic executioner
caspase-3 and -7
Yang et al., Gynecol Oncol 2005
(Adenocarcinoma...) :
Downregulation of
Xiap by antisense Xiap oligonucleotides
increased caspase-3 activity and sensitized cisplatin-resistant cells to cisplatin treatment
Vasilevskaya et al., Biochem Pharmacol 2005
(Colonic Neoplasms) :
In both cell lines, the combination also led to down-regulation of
X-linked inhibitor of apoptosis protein ( XIAP ) and enhanced
activation of
caspase-3
Kim et al., Oncogene 2005
(Glioma) :
We also found that treatment with sodium butyrate significantly decreased the protein levels of survivin and
X-linked inhibitor of apoptosis protein ( XIAP ), two major
caspase inhibitors
Kim et al., Biochem Biophys Res Commun 2005
(Insulinoma...) :
Here, we found that : ( i ) XIAP level was inversely correlated with tumor necrosis factor (TNF)-alpha induced apoptosis in MIN6N8 insulinoma cells ; ( ii ) adenoviral XIAP overexpression abrogated the TNF-alpha induced apoptosis through inhibition of
caspase activity ; ( iii ) downregulation of XIAP by antisense oligonucleotide or Smac peptide sensitized MIN6N8 cells to TNF-alpha induced apoptosis ; ( iv )
XIAP expression was
induced by TNF-alpha through a nuclear factor-kappaB (NF-kappaB) dependent pathway, and interferon (IFN)-gamma prevented such an induction in a manner independent of NF-kappaB, which presents a potential mechanism underlying cytotoxic IFN-gamma/TNF-alpha synergism
Rosato et al., Mol Cancer Ther 2005
(Leukemia) :
LAQ824/roscovitine treated cells displayed
caspase dependent down-regulation of p21 ( CIP1 ) and Mcl-1 and a pronounced caspase independent reduction in
X-linked inhibitor of apoptosis (XIAP) expression
Fraser et al., Oncogene 2006
(Ovarian Neoplasms) :
ODQ activated
caspase-3 , and ODQ induced apoptosis was
inhibited by overexpression of
X-linked inhibitor of apoptosis Protein
Mareninova et al., J Biol Chem 2006
(Disease Models, Animal...) :
Furthermore,
XIAP inhibition with embelin
triggered caspase activation in the mouse model, implicating XIAP in caspase blockade in pancreatitis
Potts et al., J Cell Biol 2005
:
Endogenous
XIAP strictly
regulates cytochrome c-dependent
caspase activation in sympathetic neurons but not in many mitotic cells
Liu et al., Mol Cancer Ther 2006
(Breast Neoplasms) :
Interestingly, the nonspecific
caspase inhibitor, z-VAD-FMK,
inhibited the down-regulation of Akt,
XIAP , and cIAP-1 in cerulenin- and LY294002 treated cells
Verhagen et al., Cell Death Differ 2007
:
Through this interaction, many are able to antagonise
XIAP inhibition of
caspase 3 in vitro
Rehm et al., EMBO J 2006
:
Sensitivity analyses predicted a critical role for
caspase-3 dependent feedback signalling and the
X-linked-inhibitor-of-apoptosis-protein ( XIAP ), but a less prominent role for the XIAP antagonist Smac
Sun et al., J Med Chem 2006
(Breast Neoplasms) :
Compound 2 binds to X-linked inhibitors of apoptosis proteins ( XIAP ) with a Ki of 61 nM in a competitive binding assay and directly antagonizes the
XIAP inhibition of
caspase-9 activity in a cell-free functional assay
Bhuiyan et al., Eur J Pharmacol 2007
(Myocardial Infarction...) :
Cardio-protection mediated by UCF-101 was correlated with reduced
X-linked inhibitor of apoptosis protein ( XIAP ) degradation and
inhibition of Caspase-9,
Caspase-3 , and Caspase-7 processing
Checinska et al., Exp Cell Res 2007
(Carcinoma, Non-Small-Cell Lung...) :
Role of
XIAP in inhibiting cisplatin induced
caspase activation in non-small cell lung cancer cells : a small molecule Smac mimic sensitizes for chemotherapy induced apoptosis by enhancing caspase-3 activation ... However, downregulation of
XIAP using shRNA or disruption of XIAP/caspase-9 interaction using a small molecule Smac mimic were unable to significantly
induce caspase-9 activity, indicating that despite a strong binding potential of XIAP to caspase-9 it is not a major determinant in blocking caspase-9 in NSCLC cells
Denault et al., Biochem J 2007
:
Our results demonstrate that cleavage by caspase 3 does not activate caspase 9, but enhances apoptosis by alleviating
XIAP inhibition of the apical
caspase
Giagkousiklidis et al., Oncogene 2007
(Pancreatic Neoplasms) :
Analysis of signaling pathways revealed that antagonizing
XIAP increased activation of
caspase-2 , -3, -8 and -9 and loss of mitochondrial membrane potential upon gamma-irradiation
Choi et al., FEBS Lett 2007
:
Our results suggest that reinforcement of the positive feedback by XIAP, which relieves
XIAP mediated
caspase-3 inhibition, might favor a pro-apoptotic cellular fate
Twiddy et al., Biochem J 2007
:
In this issue of the Biochemical Journal, Denault and co-workers evaluate the role of caspase-3 dependent cleavage of caspase-9 and conclude that this mechanism mainly serves to enhance apoptosis by alleviating
XIAP ( X-linked inhibitor of apoptosis )
inhibition of the apical
caspase
Ho et al., Mol Cell Biol 2007
:
Suppressing
XIAP with exogenous Smac/Diablo or a pharmacological inhibitor can still
induce caspase 9 in drug treated Apaf-1-null fibroblasts
Poh et al., Cell Death Differ 2007
:
This increase in TRAIL sensitivity involved mitochondrial membrane permeabilization resulting in the egress of cytochrome c and second mitochondrial activator of caspase/direct IAP binding protein with low PI, cleavage of
X-linked inhibitor of apoptosis protein , and
activation of
caspase 9
Jin et al., Biol Pharm Bull 2007
:
ABE induced apoptosis was accompanied by downregulation of antiapoptotic proteins such as
X-linked inhibitor of apoptosis protein ( XIAP ), inhibitor of apoptosis protein ( cIAP)-2 and Bcl-2,
activation of
caspase-3 , and cleavage of poly ( ADP-ribose ) polymerase ( PARP )
Gao et al., J Biol Chem 2007
:
XIAP , a ubiquitous IAP, can
inhibit both
caspase-9 , the initiator caspase of the mitochondrial apoptotic pathway, and the downstream effector caspases, caspase-3 and caspase-7 ... Smac neutralizes
XIAP inhibition of
caspase-9 by competing for binding of the BIR3 domain of XIAP with caspase-9, whereas how Smac liberates effector caspases from XIAP inhibition is not clear
Herst et al., Biochem Pharmacol 2007
:
Nevertheless, phenoxodiol inhibits proliferation of many cancer cell lines and induces apoptosis by disrupting FLICE-inhibitory protein, FLIP, expression and by
caspase dependent and -independent degradation of the
X-linked inhibitor of apoptosis , XIAP
Cillessen et al., Blood 2008
(Lymphoma, Large B-Cell, Diffuse) :
XIAP antagonist-sensitive samples were characterized by high expression levels of
XIAP , relatively low expression levels of Bcl-2, and by constitutive
caspase-9 activation
Yang et al., Cell Biol Toxicol 2008
(Leukemia, Erythroblastic, Acute) :
THDA induced apoptosis was associated with the upregulation of Bax, downregulation of
X-linked inhibitor of apoptosis (XIAP) , as well as the
activation of
caspase-3 and caspase-9 ... Moreover, the blockade of ERK and JNK also attenuated the modulation of Bax and
XIAP , as well as the
activation of caspase-3 and
caspase-9 induced by THDA
Paulsen et al., Eur J Immunol 2008
:
Interaction with
XIAP prevents full
caspase-3/-7 activation in proliferating human T lymphocytes
Li et al., Protein Sci 2008
:
Inhibition assays showed that, while
caspase-3 could be effectively
inhibited by
XIAP , survivin had no detectable inhibitory activity against the enzyme, even at concentrations several thousand-fold higher than XIAP
O'Connor et al., Biochim Biophys Acta 2008
:
Loss of
XIAP expression instead accelerated the caspase activation response, but did not
enhance the measured
caspase activity
Ferretti et al., Arthritis Rheum 2009
(Cryopyrin-Associated Periodic Syndromes...) :
The functional
effect of
XIAP on
caspase 9 activity was assessed by a fluorimetric assay, and cytokine secretion was evaluated by enzyme linked immunosorbent assay
Loeder et al., Cancer Res 2009
(Leukemia, Lymphocytic, Chronic, B-Cell) :
This
XIAP inhibitor induced and TRAIL induced apoptosis
involves caspase-3 activation and is blocked by the caspase inhibitor zVAD.fmk
Liew et al., Journal of bioscience and bioengineering 2010
:
Further investigation revealed that the
caspase-3 activity of the CHO-K1 cell line was inhibited as a
result of
XIAP expression
Dasari et al., PloS one 2010
(Glioma) :
Downregulation of
XIAP resulted in activation of
caspase-3 and caspase-9 to trigger apoptosis in glioma cells
Fellenberg et al., PloS one 2010
(Osteosarcoma) :
The observed chemoresistance was mediated at least in part by increased expression of the anti-apoptotic proteins Bcl-2, Mcl-1, and
XIAP ,
reduced activation of
caspase-9 , and, consequently, reduced cleavage of the caspase substrate PARP
Carter et al., Apoptosis 2011
(Leukemia, Myeloid, Acute...) :
XIAP , a potent
caspase inhibitor , is highly expressed in acute myeloid leukemia ( AML ) cells and contributes to chemoresistance
Kim et al., Life Sci 2011
(Disease Models, Animal...) :
The current findings demonstrate that overexpression of XIAP via in vivo delivery in an adenovirus can reduce both myocardial apoptosis and infarction following ischemia/reperfusion, at least in part, due to the ability of
XIAP to
inhibit caspase-3
Flanagan et al., Cell death & disease 2010
:
The Smac binding capacity of
XIAP , but not
caspase inhibition , was central for mitochondrial Smac retention, as evidenced in experiments using XIAP mutants that can not bind to Smac or effector caspases
Zhao et al., Asian Pac J Cancer Prev 2011
(Pancreatic Neoplasms) :
The mechanism of the apoptosis-sensitization effect appeared associated with significant up-regulation of Smac/DIABLO and cytochrome C, down-regulation of
XIAP , and
activation of
caspase-3
Li et al., Tumori 2011
(Carcinoma...) :
The synergistic effects were mediated through increased apoptotic signaling of the mitochondrial pathway, as was evident from the more increased mitochondrial depolarization,
activation of
caspase-9 and caspase-3, and suppression of
XIAP
Piacentino et al., Hum Gene Ther 2012
(Heart Failure) :
Increased
XIAP expression achieved with the SASTG vector
inhibits caspase-3/7 activity in neonatal cardiomyocytes after induction of apoptosis through three common cardiac stresses : protein kinase C-? inhibition, hypoxia, or ß-adrenergic receptor agonist
Allensworth et al., Mol Cancer Ther 2012
(Inflammatory Breast Neoplasms) :
XIAP levels and subsequent
inhibition of
caspase activity inversely correlated with TRAIL sensitivity in our models of IBC
Yuan et al., Biochem Biophys Res Commun 2012
(MAP Kinase Signaling System) :
Interestingly, X-linked inhibitor of apoptosis protein ( XIAP ) protein levels decreased in myocytes subjected to reoxygenation, and ERK phosphorylation can improve
XIAP expression, which involved
inhibiting caspase-3 , -7 and -9 activities
Buglio et al., Blood 2012
(Hodgkin Disease...) :
These molecular events were associated with the release of cytochrome c into the cytosol, down-regulation of
X-linked inhibitor of apoptosis ,
activation of
caspase 9, and induction of apoptosis
Allensworth et al., Breast Cancer Res Treat 2013
(Inflammatory Breast Neoplasms) :
X-linked inhibitor of apoptosis protein ( XIAP ), the most potent mammalian
caspase inhibitor , has been associated with acquired therapeutic resistance in inflammatory breast cancer ( IBC ), an aggressive subset of breast cancer with an extremely poor survival rate
Rajput et al., PloS one 2013
(Breast Neoplasms...) :
At molecular level, TQ and TAM synergistically lowers
XIAP expression resulting in binding and
activation of
caspase-9 in apoptotic cascade, and interfere with cell survival through PI3-K/Akt pathway by inhibiting Akt phosphorylation
Kim et al., Anticancer Res 2013
(Carcinoma, Papillary...) :
X-Linked inhibitor of apoptosis (XIAP) associated factor-1 ( XAF1 ) antagonizes
XIAP mediated
caspase inhibition
Cusack et al., Nature communications 2013
:
Additionally, cell bodies of degenerating axons are protected from
caspase activation by proteasome activity and
X-linked inhibitor of apoptosis protein
Xie et al., Cancer cell international 2013
:
The application of genistein, MDM2 inhibitor and
XIAP inhibitor to the recovering HeLa cells
caused persistent
caspase activity and enhanced cell death
Unsain et al., Cell reports 2013
:
We propose that
XIAP mediated
caspase inhibition plays an important role in regulating morphogenic events that shape the nervous system during development