Gene interactions and pathways from curated databases and text-mining

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CASP8 — CFLAR

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

Matta et al., Cancer Biol Ther 2002 (Neoplasms) : MRITalpha1/cFLIP ( L ) expression is decreased during drug induced apoptosis and exogenous expression of MRITalpha1/cFLIP ( L ) delays the activation of caspase-8 and -3 during drug- induced apoptosis
Madge et al., J Biol Chem 2003 : Cycloheximide but not LY294002 decreases expression of c-FLIP ( cellular FLICE inhibitory protein ), an inhibitor of caspase-8 activation
Tai et al., Cell Death Differ 2004 : Instead, suppression of T-cell activation in c-FLIP-transgenic T cells could be a combinatory effect of FADD/caspase-8 dependent signals and c-FLIP-specific activities
Chen et al., Biochem Biophys Res Commun 2003 : In addition, angiostatin also activated the Fas mediated apoptotic pathway in part via up-regulation of FasL mRNA, down-regulation of c-Flip , and activation of caspase 3
Vier et al., Mol Immunol 2004 : As a consequence of caspase-activation , c-FLIP-levels in the cytosol decreased
Hasegawa et al., J Biol Chem 2005 (Inflammation) : ASC mediated NF-kappaB activation leading to interleukin-8 production requires caspase-8 and is inhibited by CLARP ... This response required caspase-8 , and was suppressed by CLARP/FLIP , an inhibitor of caspase-8
Du et al., Kidney Int 2005 : Consistent with this, IL-2 but not IFN-gamma was found to decrease mRNA and protein expression of c-FLIP , an endogenous caspase-8 inhibitor in murine TECs ... Overexpression of c-FLIP in TECs ( CS3.7-FLIP ) blocked apoptosis and caspase-8 activation with both IFN-gamma and IL-2
Longley et al., Oncogene 2006 (Colorectal Neoplasms) : c-FLIP inhibits caspase 8 activation and apoptosis mediated by death receptors such as Fas and DR5
Chang et al., Cell 2006 (Liver Failure, Acute) : Here we show that TNFalpha mediated JNK activation accelerates turnover of the NF-kappaB induced antiapoptotic protein c-FLIP , an inhibitor of caspase-8
Saito et al., J Virol 2006 : A decrease in endogenous c-FLIP by specific small interfering RNA induced TNF-alpha mediated apoptotic cell death and caspase-8 activation
Huber et al., Immunology 2006 (Coxsackievirus Infections...) : c-FLIP also heterodimerizes with and activates caspase-8 , resulting in increased death of T cells and a selection of a T helper 2 cytokine profile
da Silva Correia et al., J Biol Chem 2007 : Furthermore, overexpression of CLARP , a specific caspase 8 inhibitor , completely blocked cleavage of CSN6
Wang et al., Cell Signal 2007 (Pancreatic Neoplasms) : These results indicate the role of c-FLIP and RIP in caspase-8 inhibition and thus TRAIL resistance
Dash et al., Exp Cell Res 2007 : Inhibition of cFLIP recruitment to the DISC leads to increased activation of caspase 8 and subsequently to apoptosis
Hinshaw-Makepeace et al., Eur J Immunol 2008 : Here we show that, in contrast to c-FLIP ( L ), c-FLIP ( S ) inhibits activation of caspase-8 in T cells, and consequently reduces recruitment of MALT1 and Bcl-10 to the active caspase complex
Roy et al., Proc Natl Acad Sci U S A 2008 : This molecular role for caspase-12 appears to be akin to the role of cFLIP in regulating caspase-8 in the extrinsic cell death pathway ; however, unlike cFLIP/Usurpin, we demonstrate here that caspase-12 is catalytically competent
Wang et al., Cell 2008 : Moreover, Smac mimetic induced caspase-8 activation is not blocked by endogenous c-FLIP
Luo et al., Cancer Lett 2008 : c-FLIP inhibits caspase-8 activation and cell apoptosis mediated by death receptors
Kim et al., J Cell Biochem 2008 (Kidney Neoplasms) : cFLIP inhibits caspase 8 recruitment and processing at the death inducing signaling complex ( DISC ), which is known to inhibits apoptosis mediated by death receptors such as Fas and death receptor 5 (DR5) as well as apoptosis mediated by anticancer therapeutic drugs
Ivanov et al., Cancer Res 2009 (Melanoma) : Pretreatment of several melanoma lines just before gamma-irradiation with the inhibitor of ATM kinase KU-55933 suppressed p53 and nuclear factor-kappaB (NF-kappaB) activation but notably increased radiation induced DR5 surface expression, down-regulated cFLIP ( caspase-8 inhibitor ) levels, and substantially enhanced exogenous TRAIL induced apoptosis
Klapproth et al., Blood 2009 (Burkitt Lymphoma...) : NF-kappaB up-regulates Fas and predisposes to Fas induced cell death, which is caspase-8 mediated and can be prevented by CFLAR overexpression
Eeva et al., Scand J Immunol 2009 : Fas induced apoptosis was dependent on the caspase-8 activation, since the overexpression of c-FLIP ( long ), a natural inhibitor of caspase-8 activation, blocked apoptosis induced by Fas
Tiwary et al., PloS one 2010 : Knockdown studies using siRNAs to TRAIL, DR5, JNK and CHOP as well as chemical inhibitors of ER stress and caspase-8 showed that : i ) alpha-TEA activation of DR5/caspase-8 induces an ER stress mediated JNK/CHOP/DR5 positive amplification loop ; ii ) alpha-TEA downregulation of c-FLIP ( L ) protein levels is mediated by JNK/CHOP/DR5 loop via a JNK dependent Itch E3 ligase ubiquitination that further serves to enhance the JNK/CHOP/DR5 amplification loop by preventing c-FLIP 's inhibition of caspase-8 ; and ( iii ) alpha-TEA downregulation of Bcl-2 is mediated by the ER stress dependent JNK/CHOP/DR5 signaling
Liu et al., World J Gastroenterol 2011 (Stomach Neoplasms) : In vivo, LY294002 inhibited oxaliplatin induced activation of Akt and NF?B, and increased oxaliplatin induced expression of FasL, inhibition of c-FLIP ( S ), and activation of caspase-8 , Bid, and caspase-3
Choi et al., Chem Biol Interact 2011 (Carcinoma, Renal Cell...) : Cafestol induced apoptosis is associated with the reduction of mitochondrial membrane potential ( MMP ), activation of caspase 3, cytochrome c release, and down-regulation of anti-apoptotic proteins ( Bcl-2, Bcl-xL, Mcl-1 and cFLIP )
Chen et al., J Leukoc Biol 2011 : Furthermore, tmTNF-a led to activation of caspase-8 by dissociation of cFLIP from TNFR2 and inhibition of the cFLIP expression
Bangert et al., Oncogene 2012 (Glioblastoma) : This leads to decreased recruitment of cFLIP ( L ) and cFLIP ( S ) and increased activation of caspase-8 to the TRAIL death inducing signaling complex, resulting in enhanced cleavage of caspase-8, -9 and -3 and caspase dependent apoptosis
Shi et al., Bioinformatics 2013 : cFLIP , an inhibitor of caspase-8 activation, was up-regulated briefly after 30 min of LY30 treatment, followed by a significant down-regulation over prolonged exposure
Scaffidi et al., J Biol Chem 1999 : In stably transfected BJAB cells, c-FLIP blocks caspase-8 activation at the DISC and thereby inhibits CD95 mediated apoptosis