Affinage

CFLAR

CASP8 and FADD-like apoptosis regulator · UniProt O15519

Length
480 aa
Mass
55.3 kDa
Annotated
2026-06-09
100 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CFLAR (c-FLIP) is a catalytically inert caspase-8 paralog that functions as a central cytoprotective regulator of death receptor signaling, suppressing apoptosis triggered by TNF receptor-1 and Fas/CD95 (PMID:9211860, PMID:10894163). It carries two N-terminal death effector domains fused to a caspase-like domain that lacks the catalytic active site and substrate-binding residues of caspase-8/FLICE (PMID:9211860, PMID:9380701), and it is recruited into death receptor signaling complexes through physical interactions with FADD and caspase-8 (as well as caspase-3, TRAF1, and TRAF2), positioning it upstream of caspase activation (PMID:9208847, PMID:9380701). Genetic loss in mice causes embryonic lethality with impaired heart development that phenocopies FADD- and caspase-8-null embryos, and CFLAR-deficient fibroblasts are hypersensitive to FasL/TNF-induced apoptosis with rapid caspase activation while NF-κB and JNK signaling remain intact, establishing CFLAR as a death-receptor-downstream survival factor and developmental cooperator (PMID:10894163). Beyond apoptosis, the long isoform CFLARL restrains necroptosis and autophagy, with deficiency in T lymphocytes provoking severe apoptotic and necroptotic death and enhanced cytoprotective autophagy (PMID:23392074). CFLAR also modulates inflammatory NF-κB signaling, interacting with NF-κB1 p105 to inhibit its processing to p50 (PMID:13679070) and suppressing the ASC–caspase-8–NF-κB axis by being recruited with caspase-8 to ASC speck-like aggregates (PMID:15701651). CFLARL abundance is tightly controlled by ubiquitin-dependent proteolysis: the E3 ligase ITCH drives its degradation, opposed by GMEB1-recruited deubiquitinase USP40 which removes K48-linked chains, while PRMT5 stabilizes and PRMT1 destabilizes the protein non-enzymatically by modulating ITCH binding (PMID:30736843, PMID:31046799).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Established that CFLAR is a caspase-like protein that has lost catalytic function and instead acts as a dominant-negative inhibitor of death-receptor apoptosis, defining its core paradox of structure without enzymatic activity.

    Evidence Molecular cloning, sequence/active-site analysis, and overexpression apoptosis assays against TNF-R1 and CD95 in mammalian cells

    PMID:9211860 PMID:9380701

    Open questions at the time
    • Did not resolve the molecular composition of the inhibitory complex at endogenous levels
    • Context-dependent pro- vs anti-apoptotic activity left unexplained
  2. 1997 High

    Mapped CFLAR's physical interactions to FADD, caspase-8, caspase-3, TRAF1 and TRAF2, placing it physically within the TNF-R1/Fas signaling complex.

    Evidence Reciprocal co-immunoprecipitation and deletion-mutant functional analysis in mammalian cells

    PMID:9208847 PMID:9380701

    Open questions at the time
    • Overexpression yielded both pro- and anti-apoptotic outcomes, complicating physiological interpretation
    • Stoichiometry within the DISC not determined
  3. 1998 Medium

    Identified RICK/RIP2 as a kinase binding partner that couples CFLAR to caspase-8 activation, introducing a kinase-regulated input upstream of CFLAR function.

    Evidence Co-IP, deletion mutants, and kinase-dead (K38M) dominant-negative apoptosis assays

    PMID:9575181

    Open questions at the time
    • Single lab, not independently confirmed
    • Physiological relevance of the RICK–CFLAR axis at endogenous levels untested
  4. 2000 High

    Demonstrated genetically that CFLAR is an essential cytoprotective regulator downstream of death receptors and a developmental cooperator with FADD/caspase-8, while sparing NF-κB/JNK signaling.

    Evidence casper−/− germline knockout mice with embryonic lethality, FasL/TNF apoptosis sensitivity, caspase activity and NF-κB/JNK assays in fibroblasts

    PMID:10894163

    Open questions at the time
    • Did not separate apoptotic from non-apoptotic (necroptosis/autophagy) contributions to lethality
    • Isoform-specific roles not dissected
  5. 2003 Medium

    Connected CFLAR to NF-κB control by showing it binds NF-κB1 p105 and inhibits its processing to p50, linking apoptotic and inflammatory signaling at the protein level.

    Evidence Yeast two-hybrid, co-IP in 293 cells, and NF-κB reporter assays

    PMID:13679070

    Open questions at the time
    • Single lab
    • Endogenous consequence on NF-κB target genes not established
  6. 2005 Medium

    Placed CFLAR as a suppressor of the ASC–caspase-8–NF-κB inflammatory axis, broadening its role beyond classical death receptors to inflammasome-associated signaling.

    Evidence siRNA, co-IP, confocal imaging of ASC specks, NF-κB reporter and IL-8 ELISA in stable cell lines

    PMID:15701651

    Open questions at the time
    • Single lab
    • Mechanism by which CFLAR blocks caspase-8 catalytic output at specks undefined
  7. 2013 Medium

    Showed the long isoform CFLARL coordinately restrains apoptosis, necroptosis, and autophagy, establishing CFLAR as a multi-pathway cell-death gatekeeper rather than a pure apoptosis inhibitor.

    Evidence CFLARL-deficient T cells with TCR stimulation, cell-death pathway and autophagy readouts

    PMID:23392074

    Open questions at the time
    • Single lab, commentary/review format limits method detail
    • Molecular basis of necroptosis and autophagy regulation not biochemically defined
  8. 2005 Medium

    Began defining how CFLAR protein levels are controlled, linking p53 to ubiquitin-dependent CFLARL degradation as a mechanism setting FAS apoptosis sensitivity.

    Evidence Temperature-sensitive p53 cell line, siRNA rescue, and ubiquitination Western blot with FAS agonist

    PMID:16306425

    Open questions at the time
    • E3 ligase responsible not identified in this study
    • Single lab and cell type
  9. 2019 Medium

    Resolved the ubiquitin/deubiquitin axis controlling CFLARL stability, identifying ITCH as the degrading ligase opposed by GMEB1-recruited USP40 and modulated non-enzymatically by PRMT1/PRMT5.

    Evidence Co-IP, GST pull-down, siRNA, HA-ubiquitin assays with catalytic-dead PRMT mutants, and xenograft models in cancer cells

    PMID:30736843 PMID:31046799

    Open questions at the time
    • Single lab for each axis
    • Whether PRMT methylation has any role beyond physical ITCH-binding modulation unresolved
    • Integration with p53-driven degradation not tested
  10. 2019 Low

    Extended CFLAR's cytoprotective role to tissue-injury contexts (steatohepatitis, ischemic stroke, smoke-induced airway damage), linking it to JNK, NF-κB and ER-stress responses.

    Evidence Adenoviral gain/loss-of-function in hepatocyte, MCAO/OGD, and airway epithelial models with pathway markers

    PMID:30127367 PMID:31384535 PMID:31387178

    Open questions at the time
    • Direct biochemical mechanism of CFLAR–JNK and CFLAR–ER-stress links not established
    • Effects largely phenotypic and pharmacology-driven
    • Single lab per system

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CFLAR isoform balance and post-translational regulation are integrated to switch cells between apoptosis, necroptosis, and autophagy across tissues remains unresolved.
  • No unified structural model of the CFLAR-containing inhibitory complex at endogenous stoichiometry
  • Isoform-specific (CFLARL vs CFLARS) mechanisms not systematically separated
  • Cross-talk between p53, ITCH/USP40, and PRMT regulation of CFLAR stability untested in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2
Partners
CASP8FADDGMEB1ITCHPRMT5TRAF1TRAF2USP40
Complex memberships
DISC (death-inducing signaling complex)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 I-FLICE (CFLAR) was cloned and characterized as a catalytically inert caspase-like protein that inhibits TNF receptor-1- and CD-95-induced apoptosis. It lacks both a catalytic active site and substrate binding pocket residues present in caspase-8/FLICE and caspase-10, consistent with a dominant-negative inhibitory function. Molecular cloning, sequence analysis, overexpression in mammalian cells with apoptosis assays The Journal of biological chemistry High 9211860
1997 Casper (CFLAR) physically interacts with FADD, caspase-8, caspase-3, TRAF1, and TRAF2 through distinct domains. Overexpression induces apoptosis, while a C-terminal deletion mutant inhibits TNF- and Fas-induced cell death, placing CFLAR in the TNF-R1/Fas apoptotic pathway. Co-immunoprecipitation, overexpression and deletion mutant analysis in mammalian cells, apoptosis assays Immunity High 9208847
1997 CLARP (CFLAR) contains two N-terminal death effector domains fused to a catalytically inactive caspase-like domain. It interacts with caspase-8 (but not FADD) and augments caspase-8/FADD-induced apoptosis. Its pro-apoptotic activity is blocked by the viral caspase inhibitor p35, dominant-negative caspase-8, and zVAD-fmk, placing it upstream of caspase activation. Sequence analysis, fluorogenic caspase activity assays, co-immunoprecipitation, overexpression with dominant-negative and pharmacological inhibitors in mammalian cells Proceedings of the National Academy of Sciences of the United States of America High 9380701
2000 Casper (CFLAR)-deficient mice die by embryonic day 10.5 with impaired heart development, phenocopying FADD−/− and caspase-8−/− embryos. casper−/− embryonic fibroblasts are hypersensitive to FasL- and TNF-induced apoptosis with rapid caspase activation, but NF-κB and JNK/SAPK activation remains intact, establishing CFLAR as a cytoprotective regulator downstream of death receptors and as a developmental cooperator with FADD/caspase-8. Genetic knockout (casper−/− mice), cell death assays with FasL/TNF, caspase activity assays, NF-κB and JNK activation assays in embryonic fibroblasts Immunity High 10894163
1998 RICK (RIP2) kinase physically interacts with CLARP (CFLAR) via its caspase-recruitment domain, and promotes caspase-8 activation and apoptosis induced by Fas ligand, FADD, CLARP, and caspase-8. A kinase-dead RICK mutant (K38M) functions as an inhibitor of CD95-mediated apoptosis, placing RICK as a kinase regulator upstream of CFLAR-mediated caspase-8 activation. Co-immunoprecipitation, deletion mutant analysis, kinase-dead mutant overexpression, apoptosis assays in mammalian cells The Journal of biological chemistry Medium 9575181
2003 Casper (CFLAR) physically interacts with NF-κB1 p105 through the C-terminal IκBγ domain of p105, as identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation. Overexpression of p105/IκBγ inhibits Casper-induced NF-κB activation and potentiates Casper-induced apoptosis. Additionally, Casper and its C-terminal caspase-like domain inhibit p105 processing into p50. Yeast two-hybrid screening, co-immunoprecipitation in 293 cells, overexpression assays, NF-κB reporter assays Biochemical and biophysical research communications Medium 13679070
2005 ASC-mediated NF-κB activation requires caspase-8 and is suppressed by CLARP/CFLAR. ASC recruits caspase-8 and CLARP (but not FADD) to speck-like aggregates. The catalytic activity of caspase-8 is required for ASC-mediated NF-κB activation at endogenous expression levels, placing CFLAR as an inhibitor of the ASC-caspase-8-NF-κB inflammatory signaling axis. siRNA knockdown, overexpression, co-immunoprecipitation, confocal microscopy of speck aggregates, NF-κB reporter assays, IL-8 ELISA in stable cell lines The Journal of biological chemistry Medium 15701651
2005 TRP53 (p53) modulates sensitivity to FAS-mediated apoptosis in germ cells by influencing CFLAR(L) protein stability: at the permissive p53 temperature, CFLAR(L) protein undergoes enhanced ubiquitinylation and degradation following FAS activation, whereas at non-permissive temperature CFLAR(L) accumulates. siRNA knockdown of Cflar at 37°C restored FAS-mediated apoptosis sensitivity, confirming CFLAR(L) as the effector of p53-regulated FAS resistance. Temperature-sensitive p53 cell line (GC-2spd), siRNA knockdown, Western blot for ubiquitination, real-time PCR, FAS agonistic antibody apoptosis assay Biology of reproduction Medium 16306425
2013 CFLAR long isoform (CFLARL) plays a critical role in regulating autophagy, necroptosis, and apoptosis in T lymphocytes. CFLARL-deficient T cells undergo severe cell death upon TCR stimulation involving both apoptosis and necroptosis, and autophagy is enhanced in CFLARL-deficient T cells and plays a cytoprotective function. Genetic loss-of-function (CFLARL-deficient T cells), TCR stimulation assays, cell death pathway analysis (apoptosis/necroptosis), autophagy measurement Autophagy Medium 23392074
2019 PRMT5 stabilizes CFLARL protein by decreasing its ubiquitination and inhibiting its interaction with the E3 ubiquitin ligase ITCH, while PRMT1 promotes CFLARL degradation by enhancing ITCH binding and ubiquitination. Dead (catalytically inactive) mutants of PRMT5 and PRMT1 have the same effects as wild-type, indicating that physical interaction (not enzymatic activity) mediates regulation of CFLARL stability. Co-immunoprecipitation, GST pull-down, siRNA knockdown of PRMT1/PRMT5, HA-ubiquitin overexpression with proteasomal inhibitor treatment, Western blot in lung cancer cells Journal of experimental & clinical cancer research : CR Medium 30736843
2019 GMEB1 interacts with CFLARL in the cytosol and promotes its stability by recruiting the deubiquitinase USP40, which performs K48-linked deubiquitination of CFLARL. USP40 knockdown abolishes GMEB1-mediated CFLARL stabilization. GMEB1 inhibits pro-caspase-8 activation and DISC formation upon TRAIL stimulation via CFLARL stabilization; CFLARL in turn enhances GMEB1-CASP8 binding. Co-immunoprecipitation, GST pull-down, immunofluorescence, siRNA knockdown, flow cytometry apoptosis assay, xenograft tumor model Journal of experimental & clinical cancer research : CR Medium 31046799
2018 Cigarette smoke exposure decreases CFLAR expression in bronchial epithelial cells and causes a shift in isoform balance toward c-FLIPS (consistent with necroptosis). siRNA-mediated downregulation of CFLAR in A549 cells increased baseline apoptosis and enhanced cigarette smoke extract-induced necrosis and DAMP release, establishing CFLAR as a gatekeeper against immunogenic cell death in airway epithelium. siRNA knockdown in A549 cells, apoptosis/necrosis assays, DAMP release measurement, bronchial biopsy expression analysis, isoform profiling in air-liquid interface cultures Scientific reports Medium 30127367
2019 CFLAR activates CFLAR-JNK pathway signaling to suppress JNK phosphorylation; CFLAR knockdown (via adenovirus-mediated Cflar downregulation) exacerbated lipid accumulation and oxidative stress in hepatocytes, confirming CFLAR as a functional upstream regulator of JNK phosphorylation in the context of non-alcoholic steatohepatitis. Adenovirus-mediated Cflar knockdown in NCTC-1469 cells and MCD-diet mouse model, Western blot for pJNK/CFLAR, lipid accumulation assays, oxidative stress markers Acta pharmaceutica Sinica. B Low 31384535
2019 CFLAR overexpression in mice subjected to middle cerebral artery occlusion (MCAO) reduced neurological deficit, brain water content, and infarct volume by suppressing NF-κB-mediated inflammation and ER stress markers (GRP78, PERK, ATF-6, cleaved Caspase-12). In vitro, CFLAR overexpression reduced OGD-induced cell death, while CFLAR knockdown accelerated caspase-3 cleavage in a manner reversed by ER stress blockade (4-PBA). Adenoviral CFLAR overexpression and siRNA knockdown in MCAO mouse model and OGD cell model, Western blot for NF-κB/ER stress markers, infarct volume measurement, caspase-3 cleavage assay Biomedicine & pharmacotherapy Low 31387178

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. The Lancet. Neurology 631 21216670
2000 Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Immunity 396 10894163
1997 I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis. The Journal of biological chemistry 369 9211860
1997 Casper is a FADD- and caspase-related inducer of apoptosis. Immunity 341 9208847
2003 Metabolism in the toxicokinetics and fate of brominated flame retardants--a review. Environment international 311 12850098
1997 CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis. Proceedings of the National Academy of Sciences of the United States of America 258 9380701
1998 RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. The Journal of biological chemistry 217 9575181
1994 Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether (DE-71) in C57BL/6J mice. Toxicology 212 8134923
2019 Silibinin ameliorates hepatic lipid accumulation and oxidative stress in mice with non-alcoholic steatohepatitis by regulating CFLAR-JNK pathway. Acta pharmaceutica Sinica. B 140 31384535
2017 A brain in flame; do inflammasomes and pyroptosis influence stroke pathology? Brain pathology (Zurich, Switzerland) 133 27997059
2020 CaSpER identifies and visualizes CNV events by integrative analysis of single-cell or bulk RNA-sequencing data. Nature communications 126 31900397
2007 The flame retardants, polybrominated diphenyl ethers, are pregnane X receptor activators. Toxicological sciences : an official journal of the Society of Toxicology 120 17324954
2012 Fueling the flame: bioenergy couples metabolism and inflammation. Journal of leukocyte biology 119 22571857
2010 Some flame retardants and the antimicrobials triclosan and triclocarban enhance the androgenic activity in vitro. Chemosphere 95 20943248
2002 The toxicology of the three commercial polybrominated diphenyl oxide (ether) flame retardants. Chemosphere 88 11999799
2016 The cytotoxicity of organophosphate flame retardants on HepG2, A549 and Caco-2 cells. Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering 85 27336727
2017 A defect in the mitochondrial protein Mpv17 underlies the transparent casper zebrafish. Developmental biology 73 28760346
2015 Brominated flame retardants and seafood safety: a review. Environment international 72 25700249
2009 Kindling the flame of integrin activation and function with kindlins. Current opinion in hematology 72 19553810
2017 Children's exposure to brominated flame retardants in indoor environments - A review. Environment international 71 28863388
2017 Birds and flame retardants: A review of the toxic effects on birds of historical and novel flame retardants. Environmental research 70 28193557
2018 Autoinflammatory/autoimmunity syndrome induced by adjuvants (ASIA; Shoenfeld's syndrome): A new flame. Autoimmunity reviews 69 30316995
2018 Are cell phones an indicator of personal exposure to organophosphate flame retardants and plasticizers? Environment international 69 30522823
2019 Cytotoxic and genotoxic effects of the flame retardants (PBDE-47, PBDE-99 and PBDE-209) in human bronchial epithelial cells. Chemosphere 66 31864052
2004 Analysis of Ah receptor pathway activation by brominated flame retardants. Chemosphere 66 15099731
2020 Smoking and COVID-19: Adding Fuel to the Flame. International journal of molecular sciences 65 32916821
2007 Biotransformation and cytotoxicity of a brominated flame retardant, tetrabromobisphenol A, and its analogues in rat hepatocytes. Xenobiotica; the fate of foreign compounds in biological systems 64 17620216
2020 New understanding of novel brominated flame retardants (NBFRs): Neuro(endocrine) toxicity. Ecotoxicology and environmental safety 59 33396099
2020 Bioconcentration and developmental neurotoxicity of novel brominated flame retardants, hexabromobenzene and pentabromobenzene in zebrafish. Environmental pollution (Barking, Essex : 1987) 56 33120153
2020 Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model. Archives of toxicology 55 33078273
2016 Assessing in-vitro estrogenic effects of currently-used flame retardants. Toxicology in vitro : an international journal published in association with BIBRA 54 26979758
2005 ASC-mediated NF-kappaB activation leading to interleukin-8 production requires caspase-8 and is inhibited by CLARP. The Journal of biological chemistry 54 15701651
2020 Effects of brominated and organophosphate ester flame retardants on male reproduction. Andrology 51 32216051
2018 CASH: a constructing comprehensive splice site method for detecting alternative splicing events. Briefings in bioinformatics 51 28387786
2017 Potential Glucocorticoid and Mineralocorticoid Effects of Nine Organophosphate Flame Retardants. Environmental science & technology 49 28430429
2022 Organophosphorus flame retardant TDCPP induces neurotoxicity via mitophagy-related ferroptosis in vivo and in vitro. Chemosphere 46 36087716
2020 In vitro estrogen-disrupting effects of organophosphate flame retardants. The Science of the total environment 46 32330712
2012 Targeting c-FLICE-like inhibitory protein (CFLAR) in cancer. Expert opinion on therapeutic targets 46 23252466
2019 The arginine methyltransferase PRMT5 and PRMT1 distinctly regulate the degradation of anti-apoptotic protein CFLARL in human lung cancer cells. Journal of experimental & clinical cancer research : CR 44 30736843
2019 Mesenchymal Stem Cells in Renal Fibrosis: The Flame of Cytotherapy. Stem cells international 44 30766607
2022 Inflammation and myeloid malignancy: quenching the flame. Blood 43 35468199
2018 Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release. Scientific reports 38 30127367
2013 CFLAR/c-FLIPL: a star in the autophagy, apoptosis and necroptosis alliance. Autophagy 37 23392074
2005 Influence of TRP53 status on FAS membrane localization, CFLAR (c-FLIP) ubiquitinylation, and sensitivity of GC-2spd (ts) cells to undergo FAS-mediated apoptosis. Biology of reproduction 36 16306425
2021 FLAME: A Web Tool for Functional and Literature Enrichment Analysis of Multiple Gene Lists. Biology 34 34356520
2022 Chromosome-level Thlaspi arvense genome provides new tools for translational research and for a newly domesticated cash cover crop of the cooler climates. Plant biotechnology journal 33 34990041
2020 Detrimental effects of flame retardant, PBB153, exposure on sperm and future generations. Scientific reports 33 32444626
2012 Brominated flame retardants stimulate mouse immune cells in vitro. Journal of applied toxicology : JAT 32 22972382
2021 Genetic comprehension of organophosphate flame retardants, an emerging threat to prostate cancer. Ecotoxicology and environmental safety 29 34358932
2021 Impact of brominated flame retardants on lipid metabolism: An in vitro approach. Environmental pollution (Barking, Essex : 1987) 28 34875267
2022 Anaphylatoxins spark the flame in early autoimmunity. Frontiers in immunology 27 35958588
2019 Glucocorticoid modulatory element-binding protein 1 (GMEB1) interacts with the de-ubiquitinase USP40 to stabilize CFLARL and inhibit apoptosis in human non-small cell lung cancer cells. Journal of experimental & clinical cancer research : CR 27 31046799
2018 Effect of silibinin on CFLAR-JNK pathway in oleic acid-treated HepG2 cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 30248539
2022 Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells. Cells 26 35053312
2015 An Old Flame Never Dies: Survivin in Cancer and Cellular Senescence. Gerontology 25 26159786
2021 Human CYP enzyme-activated clastogenicity of 2-ethylhexyl diphenyl phosphate (a flame retardant) in mammalian cells. Environmental pollution (Barking, Essex : 1987) 24 34380225
2020 Biomolecules as Flame Retardant Additives for Polymers: A Review. Polymers 24 32272648
2019 CFLAR is a critical regulator of cerebral ischaemia-reperfusion injury through regulating inflammation and endoplasmic reticulum (ER) stress. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 31387178
2011 Susceptibility to inhaled flame-generated ultrafine soot in neonatal and adult rat lungs. Toxicological sciences : an official journal of the Society of Toxicology 24 21914721
2023 Cellular and physiological mechanisms of halogenated and organophosphorus flame retardant toxicity. The Science of the total environment 22 37406685
2020 In Utero and Lactational Exposure to Flame Retardants Disrupts Rat Ovarian Follicular Development and Advances Puberty. Toxicological sciences : an official journal of the Society of Toxicology 22 32207525
2018 Fish energy budget under ocean warming and flame retardant exposure. Environmental research 20 29501006
2022 Organophosphate flame retardant TDCPP: A risk factor for renal cancer? Chemosphere 19 35764118
2023 The effects of brominated flame retardants (BFRs) on pro-atherosclerosis mechanisms. Ecotoxicology and environmental safety 18 37544066
2020 Organophosphorus flame retardant TDCPP-induced cytotoxicity and associated mechanisms in normal human skin keratinocytes. The Science of the total environment 18 32304943
2020 Generation of foxn1/Casper Mutant Zebrafish for Allograft and Xenograft of Normal and Malignant Cells. Stem cell reports 18 32822590
2019 Chlorinated phosphorus flame retardants exert oxidative damage to SMMC-7721 human hepatocarcinoma cells. The Science of the total environment 18 31972937
2017 Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq. Toxicology in vitro : an international journal published in association with BIBRA 18 29024780
2024 A Review of the Distribution and Health Effect of Organophosphorus Flame Retardants in Indoor Environments. Toxics 17 38535928
2023 Occurrence and risk of human exposure to organophosphate flame retardants in indoor air and dust in Hanoi, Vietnam. Chemosphere 17 37028719
2023 Flame (v2.0): advanced integration and interpretation of functional enrichment results from multiple sources. Bioinformatics (Oxford, England) 17 37540207
2021 Phenotypically Anchored mRNA and miRNA Expression Profiling in Zebrafish Reveals Flame Retardant Chemical Toxicity Networks. Frontiers in cell and developmental biology 17 33898466
2021 FLAME: long-read bioinformatics tool for comprehensive spliceome characterization. RNA (New York, N.Y.) 17 34253685
2020 Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway. Oxidative medicine and cellular longevity 17 33354276
2019 Effects of fasting on the central expression of appetite-regulating and reproductive hormones in wild-type and Casper zebrafish (Danio rerio). General and comparative endocrinology 17 31202720
2003 Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105. Biochemical and biophysical research communications 17 13679070
2023 The Organophosphate Esters Used as Flame Retardants and Plasticizers Affect H295R Adrenal Cell Phenotypes and Functions. Endocrinology 15 37522340
2023 Global patterns of human exposure to flame retardants indoors. The Science of the total environment 15 38104845
2015 Classification and toxicity mechanisms of novel flame retardants (NFRs) based on whole genome expression profiling. Chemosphere 15 26588597
2022 Developmental exposure to indoor flame retardants and hypothalamic molecular signatures: Sex-dependent reprogramming of lipid homeostasis. Frontiers in endocrinology 14 36277707
2021 Using recombinant adhesive proteins as durable and green flame-retardant coatings. Synthetic and systems biotechnology 14 34786512
2015 Elucidating toxicological mechanisms of current flame retardants using a bacterial gene profiling assay. Toxicology in vitro : an international journal published in association with BIBRA 14 26343755
2024 Epigenetic implications of common brominated flame retardants (PBDEs and TBBPA): Understanding the health risks of BFRs exposure. Chemosphere 13 38821124
2023 NMR chemical shift prediction and structural elucidation of linker-containing oligo- and polysaccharides using the computer program CASPER. Carbohydrate research 13 37734222
2022 Biphasic effects of typical chlorinated organophosphorus flame retardants on Microcystis aeruginosa. Ecotoxicology and environmental safety 13 36068742
2018 Androgen receptor modulation following combination exposure to brominated flame-retardants. Scientific reports 13 29556062
2017 Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma. Investigative ophthalmology & visual science 13 29204645
2016 New brominated flame retardants and their metabolites as activators of the pregnane X receptor. Toxicology letters 13 27506419
2016 Relationships between estimated flame retardant emissions and levels in indoor air and house dust. Indoor air 13 27614110
2015 Androgens Exert a Cysticidal Effect upon Taenia crassiceps by Disrupting Flame Cell Morphology and Function. PloS one 13 26076446
2024 Organophosphate ester flame retardants and plasticizers affect the phenotype and function of HepG2 liver cells. Toxicological sciences : an official journal of the Society of Toxicology 12 38518089
2024 Sulfolane-Based Flame-Retardant Electrolyte for High-Voltage Sodium-Ion Batteries. Nano-micro letters 12 39422856
2023 Toxicity assessment of organophosphate flame retardant triphenyl phosphate (TPHP) on intestines in mice. Ecotoxicology and environmental safety 12 37976930
2023 Reproductive toxicity of emerging plasticizers, flame retardants, and bisphenols, using culture of the rat fetal testis†. Biology of reproduction 11 36780129
2020 Bioaccumulation of legacy and emerging organophosphorus flame retardants and plasticizers in insects during metamorphosis. Journal of hazardous materials 11 33316674
2017 Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5 Cause Oculocutaneous Albinism and the casper Phenotype. G3 (Bethesda, Md.) 11 28739598
2011 Understanding cancer-induced cachexia: imaging the flame and its fuel. Current opinion in supportive and palliative care 11 21986909
2024 Cytotoxicity evaluation of organophosphorus flame retardants using electrochemical biosensors and elucidation of associated toxic mechanisms. Water research 10 39167971
2022 Estrogenic and growth inhibitory responses to organophosphorus flame retardant metabolites in zebrafish embryos. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 10 35227875
2022 Halogenated flame retardant exposure pathways in urban-adapted gulls: Are atmospheric routes underestimated? The Science of the total environment 10 36471522

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