Gene interactions and pathways from curated databases and text-mining

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CASP7 — XIAP

Pathways - manually collected, often from reviews:

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

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
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
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
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