Affinage

Showing FASLG — FASL is a alias.

FASLG

Tumor necrosis factor ligand superfamily member 6 · UniProt P48023

Length
281 aa
Mass
31.5 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FASLG (FasL/CD178/CD95L) is a type II transmembrane TNF-superfamily ligand that triggers apoptosis in Fas-bearing cells and is the non-redundant effector of activation-induced cell death (AICD) in T lymphocytes (PMID:7530337, PMID:22857792); its homozygous null mutation causes human autoimmune lymphoproliferative syndrome with intact Fas-induced apoptosis but defective reactivation-induced death (PMID:22857792). Productive death-signaling depends on ligand geometry: hexagonal FasL presentation at ~10 nm spacing drives fastest DISC-mediated apoptosis, and reduced ligand number or altered spacing impairs signaling (PMID:34057291), while aggregation state (modulated by glycosylation and the decoy receptor DcR3) tunes apoptotic potency (PMID:27806260). Downstream, FADD and caspase-8 execute killing, which proceeds through Bcl-2-dependent (type II) or Bcl-2-independent (type I) routes depending on target cell (PMID:11593384). FasL surface availability is governed by proteolytic shedding by ADAM10 — favored within palmitoylation-dependent lipid-raft nanodomains and requiring Fas–FasL contact — which generates soluble FasL and limits cytotoxicity and AICD (PMID:17290285, PMID:21368861), by an alternative MMP3-mediated cleavage downstream of osteoblast ERα signaling that solubilizes FasL to kill osteoclasts (PMID:22927007), and by endocytic internalization independent of metalloprotease shedding (PMID:11529932). Expression is controlled at multiple levels: chromatin remodeling at the HSS1 promoter site (PMID:16595663), transcriptional activation through NF-κB and Sp-1 and repression by the glucocorticoid receptor competing for an overlapping site (PMID:17192273, PMID:16770006), and post-transcriptional stabilization of FasL mRNA by HuR at 3'-UTR AU-rich elements (PMID:20675370). Beyond classical cytotoxicity, FasL mediates iNKT-cell killing (PMID:20660713), neuronal elimination of inflammatory T cells (PMID:10885654), exosome-delivered apoptosis of CD4+ T cells (PMID:24765093), adipocyte necroptosis (PMID:30546087), and platelet–red-blood-cell procoagulant signaling that promotes thrombosis (PMID:29952767). The intracellular polyproline region binds SH3-domain proteins (Grb2, FBP17, PACSIN2, Tec kinases, sorting nexins), implicated in trafficking and potential reverse signaling (PMID:12023017, PMID:19807924).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Established that FasL engagement of Fas is the molecular trigger of activation-induced T-cell death, defining the ligand-receptor axis underlying peripheral immune homeostasis.

    Evidence Soluble Fas-Ig decoy blockade and receptor crosslinking in T-cell hybridoma death assays

    PMID:7530337

    Open questions at the time
    • Did not resolve the structural geometry of receptor engagement
    • Did not address regulation of FasL surface levels
  2. 2000 Medium

    Extended FasL effector function beyond lymphocytes by showing neurons use FasL to kill encephalitogenic T cells, framing FasL as a tissue immune-privilege mechanism.

    Evidence In situ hybridization, IHC, and FasL-blocking antibody rescue in neuron/T-cell co-culture

    PMID:10885654

    Open questions at the time
    • Co-culture model, not in vivo neuroinflammation
    • Mechanism of neuronal FasL regulation not addressed
  3. 2001 Medium

    Resolved that downstream apoptosis requires FADD and caspase-8 and can be Bcl-2-dependent or independent, defining type I/type II FasL death pathways.

    Evidence Glioma cell-line panel with Bcl-2 overexpression and caspase inhibition

    PMID:11593384

    Open questions at the time
    • Cell-type basis for type I vs type II behavior not molecularly explained
  4. 2001 Medium

    Identified endocytosis, rather than metalloprotease shedding, as a route for FasL surface downregulation in activated T cells, revealing context-specific control of ligand availability.

    Evidence Endocytosis vs metalloprotease inhibitor panel on IL-2-stimulated T cells, flow cytometry

    PMID:11529932

    Open questions at the time
    • Endocytic machinery not identified
    • Apparent conflict with later ADAM10 shedding data unresolved by context
  5. 2002 Medium

    Showed the intracellular polyproline region of FasL recruits SH3-domain adaptors, opening the possibility of trafficking control and reverse signaling.

    Evidence Peptide pulldown, mass fingerprinting, and SH3 mutagenesis in T-cell lysates/overexpression

    PMID:12023017

    Open questions at the time
    • Overexpression-based interactions
    • Functional consequence for trafficking not demonstrated
  6. 2006 Medium

    Mapped multiple transcriptional and chromatin control points (HSS1 remodeling, NF-κB/Sp-1 activation, GR repression, ERK5/Foxo3a) defining how FasL expression is set.

    Evidence Promoter-reporter, EMSA, ChIP, nucleosome mapping, and kinase/transcription-factor genetic perturbation across multiple systems

    PMID:16595663 PMID:16710360 PMID:16770006 PMID:17192273

    Open questions at the time
    • Largely single-system promoter studies
    • Cross-talk integration among these inputs not established
  7. 2007 High

    Identified ADAM10 as the protease shedding FasL, establishing that ectodomain cleavage limits cytotoxic and AICD activity.

    Evidence In vitro cleavage, MEF KO/KI, pharmacological inhibition, primary human T cells

    PMID:17290285

    Open questions at the time
    • Did not define spatial/membrane control of cleavage
  8. 2010 Medium

    Linked FasL palmitoylation and lipid-raft localization to ADAM10 processing and killing efficiency, and added HuR-mediated mRNA stabilization as a post-transcriptional control.

    Evidence Palmitoylation/raft fractionation with cytotoxicity assays; RIP and 3'-UTR reporter with HuR knockdown

    PMID:20675370 PMID:21368861

    Open questions at the time
    • Palmitoyltransferase not identified
    • HuR work largely in HEK293 reporter context
  9. 2010 Medium

    Demonstrated that iNKT cytotoxicity depends almost exclusively on the Fas/FasL axis, distinguishing it from perforin-based NK killing.

    Evidence In vivo cytotoxicity in FasL-deficient gld mice with tumor protection assays

    PMID:20660713

    Open questions at the time
    • Mechanism of FasL polarization at the iNKT synapse not addressed
  10. 2011 Medium

    Placed FasL-Fas-caspase apoptosis downstream of TGF-β3/Tgfbr2 signaling in epithelial fusion, showing a developmental role via genetic epistasis.

    Evidence Tgfbr2 conditional KO with FasL/Fas inhibition and ectopic FasL rescue in palatal organ culture

    PMID:21593251

    Open questions at the time
    • Transcriptional link from TGF-β3 to FasL not defined
  11. 2012 High

    Provided the definitive human genetic proof that FasL is non-redundantly required for AICD, as null mutation causes ALPS with defective reactivation-induced death.

    Evidence FASLG sequencing, Western blot, FAS-induced apoptosis and AICD assays, plasma FasL ELISA in patient

    PMID:22857792

    Open questions at the time
    • Single homozygous case
    • Does not address partial loss-of-function phenotypes
  12. 2013 High

    Identified MMP3 as an ERα-induced alternative protease that solubilizes FasL to drive osteoclast apoptosis, broadening the proteolytic regulation of FasL beyond ADAM10.

    Evidence EGFP-FasL cleavage, MMP3 inhibitors/siRNA, ERα-KO osteoblasts, co-culture and soluble FasL ELISA

    PMID:22927007

    Open questions at the time
    • Relative contribution of MMP3 vs ADAM10 across tissues unclear
  13. 2014 Medium

    Showed FasL is delivered via exosomes as MHCII+FasL+ vesicles capable of antigen-specific T-cell killing, adding a secreted delivery mode.

    Evidence Flow cytometry, bead-based exosome capture, two apoptosis assays with LCL exosomes and autologous CD4+ T cells

    PMID:24765093

    Open questions at the time
    • In vivo relevance of exosomal FasL not established
  14. 2016 High

    Determined the FasL–DcR3 structure and showed aggregation state controls apoptotic potency, connecting molecular architecture to activity.

    Evidence X-ray crystallography with structure-guided mutagenesis and Jurkat apoptosis assays

    PMID:27806260

    Open questions at the time
    • Did not directly resolve the apoptosis-competent membrane DISC geometry
  15. 2018 High

    Expanded FasL into procoagulant and metabolic biology—platelet FasL drives RBC PS exposure and thrombosis, and osteocalcin-induced FasL triggers adipocyte necroptosis—and showed TNFα/NF-κB sensitizes hepatocytes by upregulating Fas.

    Evidence FasL/FasR KO thrombosis models, GPRC6A→CREB→FoxO1 signaling with MLKL readouts, p65 genetic/shRNA perturbation in hepatocytes in vitro and in vivo

    PMID:29952767 PMID:30185788 PMID:30546087

    Open questions at the time
    • Diverse systems with limited cross-validation
    • Switch between apoptotic and necroptotic outcomes not mechanistically unified
  16. 2021 Medium

    Defined the molecular geometry requirements for FasL signaling, showing hexagonal ~10 nm ligand spacing maximizes apoptosis, linking nanoscale ligand arrangement to DISC assembly.

    Evidence DNA origami scaffolds with systematic FasL spacing/number variation and apoptosis kinetics

    PMID:34057291

    Open questions at the time
    • Predicted hexagonal DISC architecture inferred functionally, not structurally observed in cells

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the competing fates of FasL — surface presentation, ADAM10/MMP3 shedding, endocytosis, and exosomal export — are integrated in a single cell to set output (apoptosis vs necroptosis vs reverse signaling) remains unresolved.
  • No unified model coordinating trafficking, cleavage, and SH3-adaptor reverse signaling
  • Physiological role of intracellular polyproline interactions undemonstrated
  • Determinants selecting apoptotic vs necroptotic downstream outcome unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-109582 Hemostasis 1
Partners
ADAM10DCR3FASFBP17GRB2HURMMP3PACSIN2
Complex memberships
DISC

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Receptor crosslinking of T-cell hybridomas induces Fas ligand (FasL) expression and upregulates Fas, and the ensuing engagement of Fas by FasL activates the programmed cell death programme; a soluble Fas-immunoglobulin fusion protein selectively blocks cell death but not activation, establishing FasL/Fas interaction as the molecular mechanism of activation-induced T-cell death (AICD). Soluble Fas-Ig fusion protein blockade, receptor crosslinking assays, T-cell hybridoma death assays Nature High 7530337
2007 ADAM10 (a disintegrin and metalloprotease) mediates proteolytic shedding of FasL from the cell surface, generating soluble FasL (sFasL) and membrane-bound N-terminal fragments; ADAM10 inhibition elevates FasL surface expression and increases both cytotoxic killing capacity and AICD in primary human T cells. Pharmacological inhibition, in vitro cleavage assays, loss- and gain-of-function studies in murine embryonic fibroblasts (MEFs), primary human T cell experiments Cell death and differentiation High 17290285
2002 The cytosolic polyproline region of CD95L (FasL/CD178) interacts via SH3 domain binding with Grb2, FBP17, and PACSIN2 in T-cell lysates; these interactions are abolished by mutation of the respective SH3 domains and may regulate FasL trafficking and directed expression. Peptide pulldown from T-cell lysates, peptide mass fingerprinting, co-precipitation with overexpressed constructs, SH3 domain mutagenesis FEBS letters Medium 12023017
2009 Phage display screening of a human SH3 domain library identified Tec kinases and sorting nexins as novel interaction partners of the FasL intracellular proline-rich region; interactions were verified by cellular pulldown experiments. SH3 domain phage display library screening, cellular pulldown assays BMC immunology Medium 19807924
2010 FasL palmitoylation within its transmembrane domain is critical for efficient FasL-mediated killing and for FasL processing by ADAM10; FasL processing occurs preferentially within cholesterol/sphingolipid-rich membrane nanodomains (lipid rafts), and Fas–FasL contact is required for efficient processing. Palmitoylation assays, ADAM10 cleavage assays, lipid raft fractionation, functional cytotoxicity assays Cell death & disease Medium 21368861
2006 ERK5 activation promotes cell survival by downregulating FasL expression via a mechanism involving PKB-dependent inhibition of the Forkhead transcription factor Foxo3a; loss of ERK5 or MEK5 leads to increased Foxo3a activity and elevated FasL expression that acts as a positive feedback loop enhancing apoptosis under osmotic stress. Genetic knockout of erk5 and mek5 in fibroblasts, PKB activity assays, Foxo3a activity assays, FasL expression analysis under osmotic stress Cell death and differentiation Medium 16710360
2006 MEHP-induced FasL transcription in Sertoli cells is regulated through NF-κB and Sp-1 cis-regulatory elements in the FasL promoter; MEHP exposure increases sTNF-α production, which activates NF-κB and Sp-1 via TNFR1 on Sertoli cells, causing robust FasL upregulation and germ cell apoptosis in a feed-forward mechanism. Serial deletion FasL promoter-luciferase assays, site-directed mutagenesis, EMSA, chromatin immunoprecipitation, in vitro and in vivo siRNA/TNF-α neutralization experiments The Journal of biological chemistry High 17192273
2006 The glucocorticoid receptor (GR) represses the human FasL promoter by binding to a negative glucocorticoid response element at position -990 that overlaps an NF-κB binding site, competing sterically with NF-κB for DNA binding; this represents a DNA binding-dependent mechanism of GR repression distinct from transrepression. Promoter-reporter assays, in vitro DNA binding assays, chromatin context binding assays, competition binding experiments FASEB journal Medium 16770006
2006 Active transcription of the FASLG/CD178/TNFSF6 gene in T lymphocytes requires chromatin remodeling at a hypersensitive site (HSS1, -189 to +185), where two precisely positioned nucleosomes are displaced; HSS1 remodeling precedes detectable FasL mRNA accumulation and is blocked by cycloheximide, indicating it is a primary regulatory event independent of DNA methylation or histone deacetylation at this locus. Indirect end-labeling, DNase I hypersensitivity mapping, micrococcal nuclease and restriction enzyme digestion, cycloheximide inhibition, primary and leukemia T cell comparisons The Journal of biological chemistry Medium 16595663
2010 FasL mRNA is stabilized in activated T cells through binding of the RNA-binding protein HuR to two AU-rich elements (AREs) in the FasL 3'-UTR; HuR knockdown prevents PMA-induced expression of a GFP reporter fused to the FasL 3'-UTR, demonstrating posttranscriptional regulation of FasL by HuR. Sequence analysis of 3'-UTR, in vitro and ex vivo RNA-protein interaction assays (RIP), HuR knockdown in HEK293 cells, GFP-reporter fused to FasL 3'-UTR The Journal of biological chemistry Medium 20675370
2016 Crystal structure of human FasL in complex with its decoy receptor DcR3 was determined; structure-informed mutations and native glycosylation of recombinant FasL reduce aggregation tendency and significantly enhance FasL-induced apoptosis in Jurkat cells, revealing how aggregation state modulates FasL activity. X-ray crystallography, recombinant protein production, site-directed mutagenesis, Jurkat cell apoptosis assays Structure High 27806260
2013 ERα signaling in osteoblasts induces upregulation of MMP3 expression; MMP3 cleaves and solubilizes membrane-bound FasL, and the released soluble FasL induces osteoclast apoptosis; MMP3 inhibition blocks FasL cleavage and osteoclast apoptosis, and ERα-KO osteoblasts show decreased MMP3 but not MMP7 or ADAM10 expression. EGFP-FasL cleavage assays, MMP3-specific inhibitors, siRNA knockdown of MMP3, ERα-KO mouse-derived osteoblasts, calvarial organ culture, conditioned media soluble FasL ELISA, osteoblast-osteoclast co-culture Journal of bone and mineral research High 22927007
2018 FasL on platelets directly interacts with FasR (CD95) on red blood cells (RBCs), causing phosphatidylserine (PS) externalization on RBC membranes; this enhances thrombin generation and thrombus formation. Genetic deletion or inhibition of FasL reduces PS exposure, thrombin generation, and arterial thrombosis in vivo. FasL-/- and FasR-/- mouse models, in vitro platelet-RBC interaction assays, carotid artery injury model, IVC ligation model, flow cytometry, human surgical specimens The Journal of clinical investigation High 29952767
2001 FADD and Caspase-8 are essential for FasL-induced apoptosis in glioma cells; one sensitive glioma line (D270) can be protected by anti-apoptotic Bcl-2 family members (type II behavior) while another (D645) cannot (type I behavior), demonstrating that FasL-induced apoptosis can proceed via Bcl-2-dependent or Bcl-2-independent pathways depending on cell type. Panel of seven glioma cell lines, FasL and TRAIL treatment, caspase inhibitor analysis, Bcl-2 overexpression protection assays, cycloheximide sensitization Oncogene Medium 11593384
2011 TGF-β3 signaling through Tgfβr2 in the medial edge epithelium (MEE) is required upstream of the FasL-Fas-Caspase extrinsic apoptosis pathway during palatal fusion; inhibition of the FasL-Fas system prevents MEE disappearance and caspase activity, while ectopic FasL rescues apoptosis in Tgfbr2-deficient MEE. Tgf-β3 and Tgfbr2 conditional knockout mice, FasL/Fas inhibition in palatal organ culture, ectopic FasL protein rescue experiment, caspase activity assays Journal of dental research Medium 21593251
2010 Antigen-specific cytotoxicity of invariant NKT (iNKT) cells in vivo depends almost exclusively on CD95 (Fas)/CD178 (FasL) interaction, correlating with CD1d expression level and TCR affinity for the target glycolipid; this is distinct from NK cells which rely primarily on perforin/granzyme mechanisms. In vivo cytotoxicity assays in mice, genetic deficiency models (FasL-deficient gld mice), tumor protection experiments, in vitro cytotoxicity with spleen/liver/thymus iNKT cells Journal of immunology Medium 20660713
2000 Neurons express FasL protein and mRNA; neuronal FasL induces apoptosis of co-cultured CD4+ encephalitogenic T cells, and antibodies blocking neuronal FasL protect T cells from death in co-culture, identifying neuronal FasL as a mechanism for eliminating inflammatory T cells in neuroinflammation. In situ hybridization, immunohistochemistry, hippocampal neuron/T-cell co-culture, FasL-blocking antibody experiments Brain pathology Medium 10885654
2014 Human B cell-derived lymphoblastoid cell lines (LCL) constitutively produce FasL retained intracellularly in secretory lysosomes and secreted via exosomes as MHCII+FasL+ vesicles; these LCL-derived exosomes induce antigen-specific apoptosis in autologous CD4+ T cells. Flow cytometry, bead-based exosome capture assay, two independent apoptosis assays with LCL-derived exosomes and autologous CD4+ T cells Frontiers in immunology Medium 24765093
2018 High-dose osteocalcin (GluOC) activates GPRC6A→cAMP→PKA→CREB→p300→FoxO1 signaling, leading to FasL upregulation at the plasma membrane of adipocytes; FasL engagement of Fas on neighboring adipocytes triggers MLKL phosphorylation/homotrimerization and necroptosis. Signaling pathway dissection (CREB/p300/FoxO1 activation assays), FasL expression and membrane localization analysis, MLKL phosphorylation and homotrimerization assays, 3T3-L1 adipocyte model Cell death & disease Medium 30546087
2021 DNA origami nanoagents presenting FasL in a hexagonal arrangement with 10 nm inter-molecular spacing mimic the predicted hexagonal DISC architecture and induce fastest and most efficient apoptosis signaling; reduced FasL number, altered spacing, or increased coupling flexibility impairs signaling, defining molecular geometry requirements for FasL-mediated death receptor activation. DNA origami scaffold engineering with defined FasL arrangements, cell apoptosis kinetics assays, comparison of geometric configurations Small Medium 34057291
2012 Complete FasL deficiency due to a homozygous null FASLG mutation (F87fs×95) causes autoimmune lymphoproliferative syndrome (ALPS) with absent plasma FasL, normal FAS-induced apoptosis, and defective reactivation-induced cell death, establishing that FasL is non-redundantly required for AICD in vivo. FASLG gene sequencing, Western blotting for FasL expression, FAS-induced apoptosis assay, reactivation-induced cell death (AICD) test, plasma FasL ELISA The Journal of allergy and clinical immunology High 22857792
2001 Downregulation of FasL surface expression on activated T cells proceeds via endocytosis (not metalloprotease shedding in this context); cytochalasin, sodium azide, deoxyglucose, and low temperature (endocytosis inhibitors) prevented FasL loss, while the metalloprotease inhibitor KB8301 had no effect on FasL loss or AICD in these T cells. Flow cytometry of FasL surface expression, endocytosis inhibitors, metalloprotease inhibitor KB8301, IL-2-stimulated T cells Immunology Medium 11529932
2012 HBx activates FasL expression and mediates HepG2 cell apoptosis through a MLK3→MKK7→JNK signaling module; JNK inhibitor SP600125 and MLK3 inhibitor K252a each blocked FasL upregulation and reduced apoptosis in HBx-expressing cells. HBx expression vector transfection, siRNA knockdown, Western blotting for FasL and signaling intermediates, JNK and MLK3 inhibitors, apoptosis rate measurement World journal of gastroenterology Medium 22509080
2018 TNFα sensitizes hepatocytes to FasL-induced apoptosis by transcriptionally upregulating Fas surface expression via the NF-κB pathway (p65 subunit); genetic deletion, dominant-negative inhibition, or shRNA knockdown of p65 reduces Fas expression and prevents TNFα-induced sensitization to FasL-mediated cell death both in vitro and in vivo (via hydrodynamic p65 shRNA injection). Primary hepatocytes and cell lines, p65 genetic knockout, dominant-negative inhibition, shRNA knockdown, hydrodynamic tail vein injection in mice, Fas surface expression assays Cell death & disease High 30185788

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 1391 7530337
1995 Fas and FasL in the homeostatic regulation of immune responses. Immunology today 505 8579749
2004 Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma. Journal of the National Cancer Institute 169 15240787
2017 Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance. Frontiers in immunology 165 28424702
2007 ADAM10 regulates FasL cell surface expression and modulates FasL-induced cytotoxicity and activation-induced cell death. Cell death and differentiation 161 17290285
2005 Impact of FASL-induced apoptosis in the elimination of tumor cells by NK cells. Molecular immunology 124 15607805
2012 Targeting the Fas/FasL signaling pathway in cancer therapy. Expert opinion on therapeutic targets 121 22239437
2010 Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency. Journal of immunology (Baltimore, Md. : 1950) 114 20660713
2002 The biological role of the Fas/FasL system during tumor formation and progression. Seminars in cancer biology 100 12147205
2001 Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells. Oncogene 92 11593384
2000 Neuronal FasL induces cell death of encephalitogenic T lymphocytes. Brain pathology (Zurich, Switzerland) 86 10885654
2014 Human B Cell-Derived Lymphoblastoid Cell Lines Constitutively Produce Fas Ligand and Secrete MHCII(+)FasL(+) Killer Exosomes. Frontiers in immunology 82 24765093
2019 TRAIL and FasL Functions in Cancer and Autoimmune Diseases: Towards an Increasing Complexity. Cancers 78 31072029
2001 The role of Fas and FasL as mediators of anticancer chemotherapy. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 76 11991678
2018 Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosis. The Journal of clinical investigation 75 29952767
1998 Expression of Fas (CD95) and FasL (CD95L) in human airway epithelium. American journal of respiratory cell and molecular biology 74 9761749
2021 Nanoscale FasL Organization on DNA Origami to Decipher Apoptosis Signal Activation in Cells. Small (Weinheim an der Bergstrasse, Germany) 61 34057291
2014 MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG. Molecular biology reports 61 25394756
2013 ERα signaling regulates MMP3 expression to induce FasL cleavage and osteoclast apoptosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 61 22927007
2010 Insights into the molecular regulation of FasL (CD178) biology. European journal of cell biology 61 21126798
2005 Hyperoxia-induced apoptosis and Fas/FasL expression in lung epithelial cells. American journal of physiology. Lung cellular and molecular physiology 61 16148053
2012 TRAIL but not FasL and TNFα, regulates IL-33 expression in murine hepatocytes during acute hepatitis. Hepatology (Baltimore, Md.) 58 22961755
2021 Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis. Cell death & disease 52 33980818
2006 Activation of extracellular signal-regulated protein kinase 5 downregulates FasL upon osmotic stress. Cell death and differentiation 52 16710360
2003 Biology of FasL. Cytokine & growth factor reviews 52 12787569
2009 The role of FasL and Fas in health and disease. Advances in experimental medicine and biology 51 19760067
2006 Transcriptional regulation of FasL expression and participation of sTNF-alpha in response to sertoli cell injury. The Journal of biological chemistry 51 17192273
2004 Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells. Blood 51 15339846
2018 TNFα sensitizes hepatocytes to FasL-induced apoptosis by NFκB-mediated Fas upregulation. Cell death & disease 49 30185788
2015 Downregulation of let-7e-5p contributes to endothelial progenitor cell dysfunction in deep vein thrombosis via targeting FASLG. Thrombosis research 49 26826505
2001 Apoptosis induced by FasL and TRAIL/Apo2L in the pathogenesis of thyroid diseases. Trends in endocrinology and metabolism: TEM 49 11595539
2000 Fas and Fas-L expression in Huntington's disease and Parkinson's disease. Neuropathology and applied neurobiology 49 11054182
2006 Competition between glucocorticoid receptor and NFkappaB for control of the human FasL promoter. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 46 16770006
2010 Palmitoylation of human FasL modulates its cell death-inducing function. Cell death & disease 44 21368861
2002 Genetic polymorphisms of Fas (CD95) and FasL (CD178) in human longevity: studies on centenarians. Cell death and differentiation 44 11965496
2019 miR-21-5p Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting FASLG. DNA and cell biology 43 31225740
2018 Localized immune tolerance from FasL-functionalized PLG scaffolds. Biomaterials 43 30458362
2018 Osteocalcin triggers Fas/FasL-mediated necroptosis in adipocytes via activation of p300. Cell death & disease 43 30546087
2016 Inhibition of MicroRNA-149-5p Induces Apoptosis of Acute Myeloid Leukemia Cell Line THP-1 by Targeting Fas Ligand (FASLG). Medical science monitor : international medical journal of experimental and clinical research 43 28013316
2015 Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery. Current stem cell research & therapy 43 25381758
2020 FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke. Translational stroke research 42 32036560
2012 Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutation. The Journal of allergy and clinical immunology 42 22857792
1999 New kids in the block: the role of FasL and Fas in kidney damage. Journal of nephrology 40 10440512
2005 Genetic polymorphisms of Fas (CD95) and Fas ligand (CD178) influence the rise in CD4+ T cell count after antiretroviral therapy in drug-naïve HIV-positive patients. Immunogenetics 39 16158329
2002 Identification of interaction partners of the cytosolic polyproline region of CD95 ligand (CD178). FEBS letters 39 12023017
2016 Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3. Structure (London, England : 1993) 38 27806260
2011 Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis. Apoptosis : an international journal on programmed cell death 38 21910009
2001 The regulation of FasL expression during activation-induced cell death (AICD). Immunology 38 11529932
2021 FasL+ PD-L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 34957697
2005 The C terminus of HIV-1 Tat modulates the extent of CD178-mediated apoptosis of T cells. The Journal of biological chemistry 37 16155003
2009 Role of the Fas/FasL pathway in HIV or SIV disease. Retrovirology 36 19832988
2004 Regulation of FasL expression in natural killer cells. Human immunology 36 15120186
2002 Immune privilege and FasL: two ways to inactivate effector cytotoxic T lymphocytes by FasL-expressing cells. Immunology 35 11918688
2014 miR-21 regulates N-methyl-N-nitro-N'-nitrosoguanidine-induced gastric tumorigenesis by targeting FASLG and BTG2. Toxicology letters 34 24821435
2012 HBx activates FasL and mediates HepG2 cell apoptosis through MLK3-MKK7-JNKs signal module. World journal of gastroenterology 34 22509080
2001 The Fas-FasL death receptor and PI3K pathways independently regulate monocyte homeostasis. European journal of immunology 33 11500826
2018 Inhibition of CD95/CD95L (FAS/FASLG) Signaling with APG101 Prevents Invasion and Enhances Radiation Therapy for Glioblastoma. Molecular cancer research : MCR 32 29453321
2006 FasL gene therapy: a new therapeutic modality for head and neck cancer. Cancer gene therapy 32 16543918
2000 Regulation of Fas and FasL expression on rat Schwann cells. Glia 32 10797617
2010 Systemic FasL and TRAIL neutralisation reduce leishmaniasis induced skin ulceration. PLoS neglected tropical diseases 31 20967287
2014 Fas/FasL in the immune pathogenesis of severe aplastic anemia. Genetics and molecular research : GMR 30 24938700
2021 Fas/FasL Contributes to HSV-1 Brain Infection and Neuroinflammation. Frontiers in immunology 29 34526992
1998 On the role and significance of Fas (Apo-1/CD95) ligand (FasL) expression in immune privileged tissues and cancer cells using multiple myeloma as a model. Leukemia & lymphoma 29 9922038
2010 Extreme lymphoproliferative disease and fatal autoimmune thrombocytopenia in FasL and TRAIL double-deficient mice. Blood 28 20185587
2023 CD95 (Fas) and CD95L (FasL)-mediated non-canonical signaling pathways. Biochimica et biophysica acta. Reviews on cancer 27 37865305
2015 Cutting edge: FasL(+) immune cells promote resolution of fibrosis. Journal of autoimmunity 26 25812467
2014 Targeting the Fas/FasL system in Rheumatoid Arthritis therapy: Promising or risky? Cytokine 26 25481649
2011 Tgf-beta-mediated FasL-Fas-Caspase pathway is crucial during palatogenesis. Journal of dental research 26 21593251
2008 Polymorphisms of death pathway genes FAS and FASL and risk of premalignant gastric lesions. Anticancer research 25 18383830
2009 FasL expression and reverse signalling. Results and problems in cell differentiation 24 19132323
2001 Fas-FasL in Hashimoto's thyroiditis. Journal of clinical immunology 24 11321234
2015 Decreased activation-induced cell death by EBV-transformed B-cells from a patient with autoimmune lymphoproliferative syndrome caused by a novel FASLG mutation. Pediatric research 23 26334989
2005 Perforin and Fas/FasL cytolytic pathways at the maternal-fetal interface. American journal of reproductive immunology (New York, N.Y. : 1989) 23 16212646
2003 CTLA-4. FasL induces alloantigen-specific hyporesponsiveness. Journal of immunology (Baltimore, Md. : 1950) 23 12794109
2017 Fas/FasL induces myocardial cell apoptosis in myocardial ischemia-reperfusion rat model. European review for medical and pharmacological sciences 22 28682425
2015 Fas/FasL pathway participates in regulation of antiviral and inflammatory response during mousepox infection of lungs. Mediators of inflammation 22 25873756
2021 Long non-coding RNA CASC7 suppresses malignant behaviors of breast cancer by regulating miR-21-5p/FASLG axis. Bioengineered 21 34889164
2020 Molecular mechanisms of FasL-mediated 'reverse-signaling'. Molecular immunology 21 32905906
2018 Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis - Manipulation by the electromagnetic field. PloS one 21 30286163
2007 Correlation between expression of DcR3 on tumor cells and sensitivity to FasL. Cellular & molecular immunology 21 18163957
2021 Microfluidic Tumor Vasculature Model to Recapitulate an Endothelial Immune Barrier Expressing FasL. ACS biomaterials science & engineering 20 33586426
2017 Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA. Oncotarget 20 27682872
2005 Adenovirus-mediated FasL gene transfer into human gastric carcinoma. World journal of gastroenterology 19 15948252
2019 Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis. Bioscience reports 18 31782491
2012 Altered expression of survivin, Fas and FasL contributed to cervical cancer development and metastasis. European review for medical and pharmacological sciences 18 23280017
2010 FasL gene knock-down therapy enhances the antiglioma immune response. Neuro-oncology 18 20406899
2010 FasL expression in activated T lymphocytes involves HuR-mediated stabilization. The Journal of biological chemistry 18 20675370
2009 Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC immunology 18 19807924
2006 Active transcription of the human FASL/CD95L/TNFSF6 promoter region in T lymphocytes involves chromatin remodeling: role of DNA methylation and protein acetylation suggest distinct mechanisms of transcriptional repression. The Journal of biological chemistry 18 16595663
2020 Associations of serum soluble Fas and Fas ligand (FasL) with outcomes in systemic lupus erythematosus. Lupus science & medicine 17 32546562
2011 The expression of Fas/FasL and apoptosis in yak placentomes. Animal reproduction science 17 22014664
2000 Expression of FasL and Fas protein and their soluble form in patients with hypersensitivity pneumonitis. International archives of allergy and immunology 17 10899765
2021 Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens. Frontiers in immunology 16 33841416
2012 CD4+ CD25+ Foxp3+ IFNγ+ CD178+ human induced Treg (iTreg) contribute to suppression of alloresponses by apoptosis of responder cells. Human immunology 16 23017670
2009 FAS and FASLG polymorphisms and susceptibility to idiopathic azoospermia or severe oligozoospermia. Reproductive biomedicine online 16 19146781
2013 Effects of FasL expression in oral squamous cell cancer. Asian Pacific journal of cancer prevention : APJCP 15 23534738
2011 Fas receptor (CD95) & Fas ligand (CD178) expression in patients with tobacco-related intraoral squamous cell carcinoma. The Indian journal of medical research 15 21808135
2011 Evaluation of apoptosis-related gene Fas (CD95) and FasL (CD178) polymorphisms in Iranian rheumatoid arthritis patients. Rheumatology international 15 21879377
2010 Functional polymorphisms of the FAS/FASLG genes are associated with risk of alopecia areata in a Chinese population: a case-control analysis. The British journal of dermatology 15 20394629
2006 Study of Fas (CD95) and FasL (CD178) polymorphisms in liver transplant recipients. Tissue antigens 15 16441482

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