Affinage

FAS

Tumor necrosis factor receptor superfamily member 6 · UniProt P25445

Length
335 aa
Mass
37.7 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 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

FAS (APO-1/CD95) is a death-domain-containing receptor that initiates apoptosis when oligomerized by trimeric FasL, nucleating a death-inducing signaling complex (DISC) in which the receptor C-terminal cytoplasmic tail recruits serine-phosphorylated FADD/MORT1 and downstream caspase-8 (PMID:8521815, PMID:9228058). NMR structure determination of the Fas death domain (six antiparallel amphipathic α-helices) mapped the self-association and FADD-binding surface, and disruption of this interface—by the lpr(cg) substitution or by death-domain mutations—abolishes FADD recruitment and signaling (PMID:8967952, PMID:8521815). Heterozygous death-domain mutations that block FADD binding cause autoimmune lymphoproliferative syndrome (ALPS) through dominant-negative interference with DISC formation (PMID:10200300). Two signaling tiers exist: in Type I cells abundant DISC-generated caspase-8 directly drives effector caspases independently of mitochondria, whereas in Type II cells limited DISC activity requires mitochondrial amplification and is blocked by Bcl-2/Bcl-xL (PMID:9501089). FAS surface availability is set transcriptionally—p53, and the family members TAp63/TAp73, transactivate FAS via an intronic p53-responsive element cooperating with promoter elements, sensitizing cells to apoptosis (PMID:9841917, PMID:10660538, PMID:19615968)—and post-translationally, with FAP-1 retaining Fas intracellularly to limit surface expression and Cys194 palmitoylation required for lipid-raft localization and efficient apoptosis in primary immune cells (PMID:12724420, PMID:28008916). Beyond death, FAS triggers non-apoptotic outputs including caspase-dependent JNK/SAPK activation, caspase-dependent acidic-sphingomyelinase activation and ceramide generation that is tissue-restricted (required in hepatocytes but not lymphocytes), NF-κB activation, and caspase-8-dependent maturation of IL-1β/IL-18 in myeloid cells (PMID:8950975, PMID:10200443, PMID:10722706, PMID:23144495).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1994 Medium

    Established that CD95 engagement generates a lipid second messenger, linking receptor ligation to ceramide-based signaling before the DISC was defined.

    Evidence In vivo and in vitro acidic sphingomyelinase activity assays plus C2-ceramide treatment in CD95-sensitive lines

    PMID:7523573

    Open questions at the time
    • Did not place aSMase activation relative to caspases
    • Tissue dependence of ceramide requirement not addressed
  2. 1995 High

    Defined the physical basis of FAS signal initiation by identifying the DISC and FADD/MORT1 as the recruited adaptor, answering how an oligomerized receptor transmits a death signal.

    Evidence Co-IP of APO-1-associated proteins after receptor crosslinking in T/B cell lines with mutant receptor mapping

    PMID:8521815

    Open questions at the time
    • Caspase-8 not yet shown as the enzymatic effector at the DISC
    • Quantitative differences between cell types not resolved
  3. 1995 High

    Demonstrated that FAS drives physiological activation-induced T cell death via an autocrine FasL loop, defining a functional context for the pathway.

    Evidence Blocking antibody fragments and soluble receptor decoys in Jurkat and primary T cell systems

    PMID:7530335

    Open questions at the time
    • Did not address surface vs soluble ligand control
    • In vivo relevance beyond cultured T cells not tested here
  4. 1995 Medium

    Showed that membrane FasL availability is post-translationally controlled by metalloprotease shedding, distinguishing membrane-bound from soluble ligand.

    Evidence Class-specific protease inhibitors with detection of soluble FasL in T cell lines

    PMID:7545118

    Open questions at the time
    • The responsible metalloprotease was not directly identified
    • Mechanism inferred pharmacologically
  5. 1996 High

    Provided the atomic structure of the Fas death domain and mapped the interaction surface, explaining how DISC-disrupting mutations act.

    Evidence NMR solution structure with site-directed mutagenesis

    PMID:8967952

    Open questions at the time
    • Structure of the death-domain:FADD complex not solved here
    • Higher-order oligomer geometry not defined
  6. 1996 Medium

    Separated FAS apoptotic from non-apoptotic signaling by showing NF-κB activation persists when a cytotoxicity-required tail segment is deleted.

    Evidence EMSA with C-terminal deletion mutants across multiple cell lines

    PMID:8621545

    Open questions at the time
    • Adaptors mediating the NF-κB branch not identified
    • Physiological consequences not defined
  7. 1996 Low

    Identified a candidate death-domain-associated ubiquitin-conjugating enzyme (UBC-FAP/Ubc9), raising the possibility of conjugation enzymes in FAS signaling.

    Evidence Yeast two-hybrid and co-IP with death-domain point mutant correlation

    PMID:8940097

    Open questions at the time
    • Single pulldown without functional validation of the interaction in FAS signaling
    • Causal role in apoptosis not established
  8. 1996 Medium

    Placed JNK/SAPK activation downstream of caspases and the DISC, ordering a stress-kinase branch of FAS signaling.

    Evidence c-Jun kinase assays with zVAD-fmk/CrmA epistasis and DISC IP

    PMID:8950975

    Open questions at the time
    • The specific caspase and kinase intermediates not pinned down
    • Downstream transcriptional outputs not mapped
  9. 1997 Medium

    Defined the FasL trimer–Fas binding stoichiometry and interface, and the glycosylation requirement for ligand secretion.

    Evidence FasL mutagenesis with Fas-Fc binding and cytotoxicity assays, modeled on LTα–TNFRI

    PMID:9228058

    Open questions at the time
    • No co-crystal structure of the Fas–FasL complex
    • Single lab, modeling-based interface
  10. 1997 Medium

    Connected genotoxic stress to FAS by showing ceramide induces CD95L expression and FADD-dependent apoptosis, embedding FAS in a stress-response loop.

    Evidence Antisense CD95L, dominant-negative FADD, and Niemann-Pick A fibroblasts with ceramide rescue

    PMID:9321399

    Open questions at the time
    • Direct receptor-level apoptosis remained intact in NPA cells, limiting generality
    • Quantitative ceramide thresholds not defined
  11. 1998 High

    Resolved the Type I/Type II dichotomy, explaining why mitochondrial amplification (and Bcl-2 sensitivity) governs apoptosis in some cells but not others.

    Evidence Kinetic caspase assays, Bcl-2/Bcl-xL overexpression, DISC IP, and caspase-3 reconstitution in MCF7-Fas cells

    PMID:9501089

    Open questions at the time
    • Molecular determinant of Type I vs Type II identity not defined here
    • Did not identify what limits DISC formation in Type II cells
  12. 1998 High

    Established p53 as a transcriptional inducer of FAS through an intronic p53-RE, linking DNA-damage responses to FAS-mediated drug sensitivity.

    Evidence Reporter assays, p53 binding, wt-p53 restitution in p53-null cells, and temperature-sensitive mutants

    PMID:9841917

    Open questions at the time
    • Did not separate sensitization from direct induction
    • Other transcription factors at the locus not surveyed
  13. 1998 Medium

    Identified NO-mediated S-nitrosylation of caspase-8/-1 as a brake on FAS apoptosis acting at the caspase level.

    Evidence NO donors and iNOS transfection with caspase cleavage and S-nitrosylation assays, cGMP-independent

    PMID:9607562

    Open questions at the time
    • Physiological NO sources controlling FAS not defined
    • Single lab
  14. 1998 Medium

    Showed PKC restrains FAS by inhibiting receptor oligomerization at the surface, defining a pre-DISC regulatory node.

    Evidence PKC activators/inhibitors with CD95 aggregation and UVB-apoptosis readouts in Jurkat cells

    PMID:10528172

    Open questions at the time
    • Direct PKC substrate on the oligomerization machinery not identified
    • Single cell system
  15. 2000 Medium

    Ordered the ceramide branch by placing aSMase activation downstream of initiator caspases during the initiation phase of apoptosis.

    Evidence Dominant-negative FADD and CrmA with aSMase activity, ceramide, and JNK/p38 assays; titrated caspase-8 expression and mass spectrometry

    PMID:10200443 PMID:10722705

    Open questions at the time
    • Direct caspase substrate activating aSMase not identified
    • Single lab
  16. 2000 High

    Defined the ceramide pathway as tissue-restricted, showing aSMase is required for FAS-induced hepatocyte but not lymphocyte death.

    Evidence aSMase-/- mice challenged with anti-Fas in vivo and in vitro, comparing hepatocytes and lymphocytes

    PMID:10722706

    Open questions at the time
    • Molecular basis of the hepatocyte-specific requirement not defined
    • Did not address aSMase role in non-apoptotic FAS signaling
  17. 2000 Medium

    Showed the intronic FAS p53-RE is engaged even by apoptosis-defective p53 mutants, distinguishing FAS as a sensitization rather than direct apoptosis-inducing target.

    Evidence Reporter and p53 binding assays in mammalian and yeast systems with discriminatory p53 mutants

    PMID:10660538

    Open questions at the time
    • Endogenous chromatin context not tested
    • Single lab
  18. 2003 Medium

    Identified FAP-1 as a post-translational regulator that retains Fas intracellularly and limits surface expression, with Cys275 controlling the interaction.

    Evidence FAP-1 overexpression, dominant-negative, and siRNA with surface-Fas flow cytometry, confocal microscopy, and mutation analysis

    PMID:12724420

    Open questions at the time
    • Mechanism of cytoskeletal retention not detailed
    • In vivo relevance not addressed
  19. 2003 Medium

    Revealed maturation-dependent divergence of FAS signaling in myeloid cells: caspase-dependent cytokine output in monocytes versus caspase-independent responses in macrophages.

    Evidence Fas ligation on primary monocytes/macrophages with cytokine ELISA, NF-κB translocation, and caspase inhibitors

    PMID:12794152

    Open questions at the time
    • Molecular switch underlying maturation-state divergence not defined
    • Single lab
  20. 2005 Medium

    Identified CD47 as a Fas-associated co-factor that augments Fas apoptosis via the mitochondrial branch.

    Evidence CD47-deficient Jurkat and CD47-null primary T cells with Fas–CD47 co-IP, caspase/PARP cleavage, cytochrome c release, and ΔΨm assays

    PMID:15917238

    Open questions at the time
    • Whether the Fas–CD47 association is direct vs complex-mediated not resolved
    • Structural basis not defined
  21. 2012 High

    Established a non-apoptotic FAS function: caspase-8-dependent IL-1β/IL-18 maturation in myeloid cells independent of inflammasomes or RIP3.

    Evidence RIP3-/- and caspase-1-/- cells with FasL stimulation, cytokine maturation, and caspase-8 activation assays

    PMID:23144495

    Open questions at the time
    • Direct caspase-8 substrate for cytokine processing not pinned down
    • In vivo contribution to inflammation not quantified
  22. 2013 Medium

    Showed FAS-induced apoptosis is proinflammatory, generating chemokine 'find-me' signals requiring RIPK1 and IAPs.

    Evidence Cytokine/chemokine profiling, chemotaxis and phagocyte recruitment assays with RIPK1 knockdown and IAP antagonists

    PMID:23434371

    Open questions at the time
    • Mechanism coupling RIPK1/IAPs to specific chemokines not detailed
    • Single lab
  23. 2016 High

    Demonstrated that Cys194 palmitoylation drives Fas into lipid rafts and is required for efficient apoptosis in primary immune cells, separating death from non-apoptotic functions in vivo.

    Evidence C194V knock-in mice with palmitoylation assay, raft fractionation, primary-cell apoptosis, and autoimmunity phenotyping

    PMID:28008916

    Open questions at the time
    • The palmitoyl transferase acting on Fas not identified
    • How raft localization mechanistically enhances DISC assembly not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular determinant that assigns cells to Type I versus Type II FAS signaling, and the rules governing the switch between apoptotic and the diverse non-apoptotic outputs (NF-κB, JNK, ceramide, cytokine maturation), remain unresolved.
  • No defined factor predicting Type I vs Type II identity
  • Switch between death and inflammatory/proliferative outputs not mechanistically specified
  • Palmitoyl transferase and raft-assembly machinery for Fas unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2
Partners
CASP8CD47FADDFAP1FASL
Complex memberships
DISC (death-inducing signaling complex)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Upon APO-1/Fas (CD95) oligomerization, cytotoxicity-dependent APO-1-associated proteins (CAP1-4) are recruited to form a death-inducing signaling complex (DISC) with the aggregated receptor. CAP1 and CAP2 were identified as serine-phosphorylated MORT1/FADD. Association required the C-terminal cytoplasmic tail of APO-1 and was abolished by the lpr(cg) amino acid replacement in the death domain. Immunoprecipitation of APO-1-associated proteins from T and B cell lines after receptor crosslinking; mutant receptor analysis The EMBO journal High 8521815
1996 The NMR solution structure of the Fas death domain was determined: it consists of six antiparallel amphipathic alpha-helices in a novel fold. Site-directed mutagenesis identified the surface region involved in death-domain self-association and in binding to the downstream signaling partner FADD. NMR spectroscopy; site-directed mutagenesis Nature High 8967952
1998 Two distinct CD95 signaling pathways exist: in Type I cells, caspase-8 is activated rapidly and in large amounts at the DISC, bypassing mitochondria (Bcl-2/Bcl-xL overexpression does not block apoptosis); in Type II cells, DISC formation is reduced, caspase activation depends on mitochondrial membrane potential loss (ΔΨm), and Bcl-2/Bcl-xL overexpression blocks both caspase activation and apoptosis. Kinetic caspase activation assays, Bcl-2/Bcl-xL overexpression, DISC immunoprecipitation, caspase-3 reconstitution in MCF7-Fas cells The EMBO journal High 9501089
1994 CD95 crosslinking activates an acidic sphingomyelinase (optimal pH 5.0), causing sphingomyelin hydrolysis and ceramide generation. Cell-permeant ceramide analogue C2-ceramide was sufficient to induce apoptosis in CD95-sensitive lines, suggesting ceramide is an early intracellular signal downstream of CD95. In vivo sphingomyelin hydrolysis assay; direct in vitro enzymatic activity measurement with labeled SM vesicles; ceramide treatment The Journal of experimental medicine Medium 7523573
1995 TCR-induced apoptosis in human T cells (Jurkat, alloreactive clone S13, peripheral activated T cells) is mediated by autocrine CD95L: TCR stimulation induces CD95L expression and secretion of soluble CD95L, and apoptosis is blocked by anti-APO-1 antibody fragments or soluble APO-1 receptor decoys. Functional blocking antibodies; single-cell cultures; soluble receptor decoy competition; CD95L detection in supernatant Nature High 7530335
1995 Cell surface expression of APO-1 ligand (FasL) is regulated by Zn2+-dependent metalloproteases: metalloprotease inhibitors increase surface FasL accumulation, indicating that metalloprotease cleavage generates the soluble form of FasL and limits membrane-bound FasL. Immunofluorescence with class-specific protease inhibitors; antibody detection of soluble FasL; Zn2+/Ca2+ modulation European journal of immunology Medium 7545118
1998 p53 transcriptionally activates the CD95 receptor gene by binding to a p53-responsive element in the first intron of CD95 and cooperating with promoter elements, thereby upregulating CD95 surface expression in response to DNA-damaging anticancer drugs. This sensitizes cells to CD95-mediated apoptosis. Mutant p53 failed to induce CD95 upregulation. Reporter gene assays with p53-RE constructs; p53 binding assays; restitution of wt p53 in p53-null cells; temperature-sensitive p53 mutants The Journal of experimental medicine High 9841917
1996 CD95 engagement activates NF-κB DNA-binding activity independently of its cytotoxic function: a C-terminal 37-amino-acid deletion in the CD95 cytoplasmic domain that abrogates apoptosis only marginally affects NF-κB activation. Electrophoretic mobility shift assay (EMSA); deletion mutant analysis in multiple cell lines The Journal of biological chemistry Medium 8621545
1996 CD95-triggered activation of stress-activated protein kinases (JNK/SAPK, 46 kDa and 54 kDa) occurs downstream of ICE-like proteases (caspases) and downstream of DISC formation: caspase inhibitor zVAD-fmk and CrmA blocked SAP kinase activation but not DISC formation, placing caspases between DISC and SAP kinases. Kinase assays (phosphorylation of c-Jun); caspase inhibitor (zVAD-fmk, CrmA overexpression); DISC immunoprecipitation Oncogene Medium 8950975
1997 The FasL homotrimer binds three Fas molecules. Point mutations at the FasL–Fas interaction interface (P206, Y218, F275/gld) reduced or abolished Fas binding and cytotoxicity; F275L (gld equivalent) caused aggregation and loss of Fas binding. Glycosylation of FasL N-linked glycans was required for efficient secretion. Site-directed mutagenesis of FasL; binding assays with recombinant Fas-Fc fusion; cytotoxicity assays; molecular modeling based on LTα–TNFRI structure The Journal of biological chemistry Medium 9228058
1999 In autoimmune lymphoproliferative syndrome (ALPS), heterozygous CD95 death-domain mutations cause structural alterations that abolish FADD/MORT1 binding. Despite heterozygosity, lymphocytes from ALPS patients show markedly reduced FADD association and loss of caspase recruitment after CD95 crosslinking, establishing dominant-negative interference with DISC formation. Co-IP of FADD with CD95 from patient lymphocytes; caspase recruitment assay; structural analysis of nine independent death-domain mutations Proceedings of the National Academy of Sciences of the United States of America High 10200300
1997 Ceramide links cellular stress responses (gamma-irradiation, doxorubicin) to CD95-mediated apoptosis: ceramide induces CD95L expression and apoptosis; antisense CD95L and dominant-negative FADD block ceramide-induced and stress-induced apoptosis. Fibroblasts from Niemann-Pick type A patients (lacking ceramide synthesis) fail to upregulate CD95L and resist apoptosis after irradiation/doxorubicin but can still undergo apoptosis when directly triggered through CD95. Antisense CD95L; dominant-negative FADD transfection; genetically deficient NPA fibroblasts; exogenous ceramide rescue The EMBO journal Medium 9321399
1998 Fas/CD95-triggered acidic sphingomyelinase activation, ceramide release, and subsequent JNK/p38 kinase activation are regulated downstream of caspases: caspase inhibition (Ac-YVAD-cmk or CrmA) prevented aSMase activation and ceramide generation, placing caspases upstream of aSMase in the CD95 signaling cascade. Caspase inhibitor (Ac-YVAD-cmk); CrmA transfection; aSMase activity assay; ceramide measurement; JNK/p38 kinase assay Cell death and differentiation Medium 10200443
2000 Acid sphingomyelinase (aSMase) is required for Fas-mediated cell death in hepatocytes but not in thymocytes, T cells, or B cells: aSMase-/- mice showed protection from anti-Fas-induced hepatocyte apoptosis and mortality, while lymphocyte apoptosis and activation-induced cell death were unaffected by aSMase status. Genetically engineered aSMase-/- mice; in vitro and in vivo anti-Fas antibody challenge; comparison of hepatocyte vs. lymphocyte apoptosis The Journal of biological chemistry High 10722706
2000 Ceramide generation downstream of CD95 is initiator-caspase-dependent and occurs during the initiation phase of apoptosis, prior to the effector phase: dominant-negative FADD blocked ceramide generation; CrmA blocked FADD-induced ceramide elevation; limited pro-caspase-8 expression raised ceramide without causing apoptosis. Titrated FADD transfection in HeLa and 293T cells; dominant-negative FADD; CrmA; diacylglycerol kinase assay; electrospray tandem mass spectrometry for ceramide The Journal of biological chemistry Medium 10722705
2003 FAP-1 (Fas-associated phosphatase 1) binds the C-terminus of Fas and retains it intracellularly within the cytoskeleton network, reducing cell surface Fas expression. Dominant-negative FAP-1 or FAP-1 siRNA upregulates surface Fas. A Fas C275 mutation decreases FAP-1 association and increases Fas surface export. FAP-1 overexpression/dominant-negative transfection; siRNA knockdown; flow cytometry for surface Fas; confocal microscopy; mutation analysis Molecular and cellular biology Medium 12724420
2012 FAS/CD95 mediates noncanonical IL-1β and IL-18 maturation in macrophages and dendritic cells via caspase-8 activation, independently of inflammasomes or RIP3. TLR ligand priming upregulates Fas expression and renders cells responsive to FasL-mediated caspase-8 activation and IL-1β/IL-18 processing. Genetic knockout cells (RIP3-/-, caspase-1-/-); FasL stimulation of macrophages and DCs; IL-1β/IL-18 maturation assay; caspase-8 activation assay Journal of immunology (Baltimore, Md. : 1950) High 23144495
2013 Fas/CD95-induced apoptosis is accompanied by production of chemokines (MCP-1, IL-8, CXCL1, IL-6, GMCSF) that serve as 'find-me' signals promoting phagocyte chemotaxis toward apoptotic cells. RIPK1 and IAPs are required for optimal Fas-induced cytokine/chemokine production; IAP antagonists suppress this proinflammatory response. Cytokine/chemokine profiling after Fas stimulation; chemotaxis assay; RIPK1 knockdown; IAP antagonist treatment; phagocyte recruitment assay Molecular cell Medium 23434371
1998 Nitric oxide (NO) inhibits APO-1/Fas-mediated apoptosis by S-nitrosylating caspase-8 and caspase-1, preventing their activation. NO blocks proteolytic cleavage of caspase-3 upstream of its activation. The effect is cGMP-independent and also inhibits apoptosis induced by FADD overexpression. NO donor and inducible NOS transfection; caspase-3 cleavage assay; caspase-8 S-nitrosylation assay; FADD overexpression apoptosis assay; 8-bromo-cGMP control Cell growth & differentiation Medium 9607562
2000 Human and mouse Fas/CD95 genes each contain a p53-responsive element (p53RE) in the first intron that is specifically bound by p53 and functions as a p53-dependent enhancer. Unlike the bax p53RE, the Fas p53RE is activated by p53 mutants that cannot induce apoptosis (Pro-175 and Ala-143), suggesting Fas upregulation by p53 sensitizes to apoptosis rather than directly inducing it. Reporter gene assays in mammalian and yeast systems; p53 binding assays; discriminatory p53 mutant analysis The Journal of biological chemistry Medium 10660538
2009 TAp63 and TAp73 isoforms of the p53 family, in addition to wt p53, transactivate the CD95/FAS gene through the intronic p53-responsive element and promoter p53-REs, with cooperation between intronic and promoter elements required for maximal transcriptional activation. Reporter gene assays with p53-RE constructs; p63/p73 isoform expression Biochemical and biophysical research communications Medium 19615968
1996 A novel ubiquitin-conjugating enzyme (UBC-FAP/HsUbc9) associates with the Fas death domain. A single amino acid substitution in the Fas death domain that abolishes apoptosis also abolishes Fas–UBC-FAP association, suggesting UBC-FAP may participate in Fas signal transduction. Yeast two-hybrid screen; co-immunoprecipitation; complementation of ubc9-1 yeast mutant; death-domain point mutant analysis The Journal of biological chemistry Low 8940097
2005 CD47 (integrin-associated protein) physically associates with Fas upon Fas activation and augments Fas-mediated apoptosis: Jurkat cells lacking CD47 are resistant to Fas-mediated death and show impaired caspase activation, cytochrome c release, loss of mitochondrial membrane potential, and DNA cleavage downstream of Fas engagement. CD47-deficient Jurkat cells; anti-Fas co-immunoprecipitation showing Fas–CD47 association; caspase and PARP cleavage assays; mitochondrial membrane potential assay; CD47-null primary mouse T cells The Journal of biological chemistry Medium 15917238
1998 Protein kinase C (PKC) inhibits CD95 receptor oligomerization at the cell surface as a mechanism for restraining CD95-mediated apoptosis; PKC activation diminishes CD95 aggregation induced by agonistic antibodies and UVB-induced CD95 oligomerization and apoptosis in Jurkat T cells. PKC activators (PMA) and inhibitors; CD95 aggregation assay; UVB-induced apoptosis; MAP kinase pathway inhibition Journal of immunology (Baltimore, Md. : 1950) Medium 10528172
2016 Fas-mediated apoptosis in primary mouse T cells, B cells, and dendritic cells requires receptor palmitoylation at Cys194 for lipid raft localization: a palmitoylation-defective Fas C194V mutant fails to efficiently induce apoptosis in primary immune cells despite retaining ability to enhance T-cell differentiation and to prevent lymphoaccumulation and autoimmunity. Knock-in C194V mutant mice; palmitoylation assay; lipid raft fractionation; apoptosis assays in primary immune cells; lymphoproliferation phenotype analysis Nature communications High 28008916
2003 Fas (CD95) ligation on human monocytes induces proinflammatory cytokine (TNF-α, IL-8) production and NF-κB nuclear translocation through a caspase-dependent mechanism, while in monocyte-derived macrophages Fas-induced cytokine responses occur without apoptosis and are caspase-independent, demonstrating maturation-dependent divergence in Fas signaling. Fas ligation on primary monocytes and macrophages; ELISA for TNF-α and IL-8; NF-κB nuclear translocation; caspase inhibitor treatment; neutrophil chemotaxis assay Journal of immunology (Baltimore, Md. : 1950) Medium 12794152

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Two CD95 (APO-1/Fas) signaling pathways. The EMBO journal 2423 9501089
1995 Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. The EMBO journal 1732 8521815
1995 Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 1555 7530335
1996 Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science (New York, N.Y.) 1075 8910274
1996 Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nature medicine 931 8616718
2003 The CD95(APO-1/Fas) DISC and beyond. Cell death and differentiation 839 12655293
1996 Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion? Nature medicine 833 8946836
1998 p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. The Journal of experimental medicine 714 9841917
1995 Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. The EMBO journal 664 8557033
1995 Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. The Journal of experimental medicine 629 7595193
1994 Apoptotic signaling through CD95 (Fas/Apo-1) activates an acidic sphingomyelinase. The Journal of experimental medicine 527 7523573
1996 Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils. The Journal of experimental medicine 508 8760796
1998 Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis. Current opinion in immunology 402 9794832
1997 The CD95 (APO-1/Fas) system mediates drug-induced apoptosis in neuroblastoma cells. Cancer research 397 9288794
1996 NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain. Nature 314 8967952
1997 Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors. Cancer research 306 9354463
1997 Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis. The EMBO journal 266 9321399
2011 Regulation of CD95/Fas signaling at the DISC. Cell death and differentiation 265 22075988
2012 Cutting edge: FAS (CD95) mediates noncanonical IL-1β and IL-18 maturation via caspase-8 in an RIP3-independent manner. Journal of immunology (Baltimore, Md. : 1950) 257 23144495
1996 Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain. The Journal of experimental medicine 251 8879222
1997 CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology 221 9207274
2001 Fas (CD95) induces alveolar epithelial cell apoptosis in vivo: implications for acute pulmonary inflammation. The American journal of pathology 219 11141488
1999 Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer. Oncogene 210 10391683
1998 Involvement of the CD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis. The Journal of clinical investigation 209 9788963
2000 Involvement of CD95/Apo1/Fas in cell death after myocardial ischemia. Circulation 198 10952962
1995 Regulation of cell surface APO-1/Fas (CD95) ligand expression by metalloproteases. European journal of immunology 195 7545118
1995 Local Fas/APO-1 (CD95) ligand-mediated tumor cell killing in vivo. European journal of immunology 189 7545115
1998 Induction of Fas (Apo-1, CD95)-mediated apoptosis of activated lymphocytes by polyclonal antithymocyte globulins. Blood 187 9516135
1996 Fas/APO-1/CD95 system as a mediator of granulosa cell apoptosis in ovarian follicle atresia. Endocrinology 186 8612534
1995 Functional expression of Fas antigen (CD95) on hematopoietic progenitor cells. Blood 186 7542501
2013 Fas/CD95-induced chemokines can serve as "find-me" signals for apoptotic cells. Molecular cell 184 23434371
1997 Deficient activation of the CD95 (APO-1/Fas) system in drug-resistant cells. Leukemia 179 9369415
2000 Death the Fas way: regulation and pathophysiology of CD95 and its ligand. Pharmacology & therapeutics 173 11337030
1997 Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. The Journal of biological chemistry 165 9228058
1999 Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia. Proceedings of the National Academy of Sciences of the United States of America 150 10200300
2003 Fas (CD95) induces proinflammatory cytokine responses by human monocytes and monocyte-derived macrophages. Journal of immunology (Baltimore, Md. : 1950) 143 12794152
1997 Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic syndromes. Leukemia 140 9177438
1995 Fas/APO-1 gene transfer for human malignant glioma. Cancer research 135 7540953
1996 The CD95 (APO-1/Fas) receptor activates NF-kappaB independently of its cytotoxic function. The Journal of biological chemistry 128 8621545
1996 CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases. Oncogene 125 8950975
1995 Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo. International immunology 123 7495753
2000 Fas (CD95/APO-1) plays a role in the pathophysiology of focal cerebral ischemia. Journal of neuroscience research 122 10972965
1997 Fas/APO-1 (CD95) is not translocated to the cell membrane in esophageal adenocarcinoma. Cancer research 122 9407969
1998 Mutation of CD95 (Fas/Apo-1) gene in adult T-cell leukemia cells. Blood 119 9573032
1998 Activation of the CD95 (APO-1/Fas) pathway in drug- and gamma-irradiation-induced apoptosis of brain tumor cells. Cell death and differentiation 118 10203687
1997 Constitutive expression of Fas (Apo-1/CD95) ligand on multiple myeloma cells: a potential mechanism of tumor-induced suppression of immune surveillance. Blood 118 9207432
2000 Role of acidic sphingomyelinase in Fas/CD95-mediated cell death. The Journal of biological chemistry 116 10722706
1999 Alterations of Fas (Apo-1/CD95) gene in cutaneous malignant melanoma. The American journal of pathology 112 10362803
2000 Human and mouse Fas (APO-1/CD95) death receptor genes each contain a p53-responsive element that is activated by p53 mutants unable to induce apoptosis. The Journal of biological chemistry 109 10660538
1999 Alterations of Fas (APO-1/CD95) gene in transitional cell carcinomas of urinary bladder. Cancer research 109 10397246
1998 Fas/CD95/Apo-I activates the acidic sphingomyelinase via caspases. Cell death and differentiation 108 10200443
1995 Expression of Fas/APO-1 during the progression of astrocytomas. Cancer research 100 7585627
1999 Dendritic cells are resistant to apoptosis through the Fas (CD95/APO-1) pathway. Journal of immunology (Baltimore, Md. : 1950) 95 10553053
1998 CD95 (Fas/APO-1) induces ceramide formation and apoptosis in the absence of a functional acid sphingomyelinase. The Journal of biological chemistry 94 9516458
2003 FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface. Molecular and cellular biology 88 12724420
2003 Function and regulation of the CD95 (APO-1/Fas) ligand in the immune system. Seminars in immunology 86 14563113
1996 CD95 (APO-1/Fas)-associating signalling proteins. Cell death and differentiation 80 17180078
1995 Expression and function of Fas (APO-1/CD95) in patient myeloma cells and myeloma cell lines. Blood 79 7540067
1999 NF-kappaB regulates Fas/APO-1/CD95- and TCR- mediated apoptosis of T lymphocytes. European journal of immunology 78 10092091
1998 Nitric oxide inhibits APO-1/Fas-mediated cell death. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 78 9607562
2003 Fas (CD95/Apo-1) ligand regulation in T cell homeostasis, cell-mediated cytotoxicity and immune pathology. Seminars in immunology 77 14563115
2000 CD95(Fas/APO-1) signals ceramide generation independent of the effector stage of apoptosis. The Journal of biological chemistry 74 10722705
1998 Expression of Fas (CD95) and FasL (CD95L) in human airway epithelium. American journal of respiratory cell and molecular biology 74 9761749
2000 T cell activation-induced and HIV tat-enhanced CD95(APO-1/Fas) ligand transcription involves NF-kappaB. European journal of immunology 73 10671224
2005 Fas (CD95)-related apoptosis and rheumatoid arthritis. Rheumatology (Oxford, England) 67 16159946
1997 Expression and function of Fas (CD95) on human renal tubular epithelial cells. Journal of the American Society of Nephrology : JASN 67 9335379
1997 Expression and function of CD95 (FAS/APO-1) in leukaemia-lymphoma tumour lines. British journal of haematology 66 9054667
2017 Nonapoptotic functions of Fas/CD95 in the immune response. The FEBS journal 65 29032605
2005 CD47 augments Fas/CD95-mediated apoptosis. The Journal of biological chemistry 65 15917238
1998 Immune evasion by tumours: involvement of the CD95 (APO-1/Fas) system and its clinical implications. Molecular medicine today 63 9547792
1994 The APO-1/Fas (CD95) receptor is expressed in homozygous MRL/lpr mice. European journal of immunology 63 7528670
2004 Carbon monoxide promotes Fas/CD95-induced apoptosis in Jurkat cells. The Journal of biological chemistry 62 15280387
1999 Death receptor Fas/Apo-1/CD95 expressed by human placental cytotrophoblasts does not mediate apoptosis. Biology of reproduction 61 10208976
2002 Frequent downregulation of Fas (CD95) expression and function in melanoma. Melanoma research 60 12140383
1998 Inhibition of Fas (CD95) expression and Fas-mediated apoptosis by oncogenic Ras. Cancer research 60 9699671
2016 Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction. Nature communications 59 28008916
1998 Necrogenesis and Fas/APO-1 (CD95) expression in primary (de novo) and secondary glioblastomas. Journal of neuropathology and experimental neurology 58 9600216
2006 Hypoxia induces p53-dependent transactivation and Fas/CD95-dependent apoptosis. Cell death and differentiation 56 16917513
1995 Expression of Fas/Apo-1 (CD95) and apoptosis in tumor cells from patients with plasma cell disorders. Blood 55 7544648
2000 CD95 (Fas/APO-1) and p53 signal apoptosis independently in diverse cell types. Cancer research 54 10728678
1999 Involvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation. Gastroenterology 53 10029626
1996 Association of human fas (CD95) with a ubiquitin-conjugating enzyme (UBC-FAP). The Journal of biological chemistry 53 8940097
2001 Regulation of CD95 (Fas/APO-1)-induced apoptosis in human chondrocytes. Arthritis and rheumatism 51 11465715
1999 Protein kinase C inhibits CD95 (Fas/APO-1)-mediated apoptosis by at least two different mechanisms in Jurkat T cells. Journal of immunology (Baltimore, Md. : 1950) 51 10528172
1996 Comparison of Fas(Apo-1/CD95)- and perforin-mediated cytotoxicity in primary T lymphocytes. International immunology 51 8671589
1995 Regulation of Fas(Apo-1/CD95)- and perforin-mediated lytic pathways of primary cytotoxic T lymphocytes by the protooncogene bcl-2. European journal of immunology 50 8566045
2011 Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 21209208
1998 CD95 (APO-1/FAS)-mediated apoptosis in cytokine-activated hematopoietic cells. Experimental hematology 45 9694505
1997 Metallothionein and Fas (CD95) are expressed in squamous cell carcinoma of the tongue. European journal of cancer (Oxford, England : 1990) 45 9470847
1998 Protein kinase C regulates Fas (CD95/APO-1) expression. Journal of immunology (Baltimore, Md. : 1950) 44 9725212
1996 CD95 (Fas/Apo-1)-induced apoptosis results in loss of glucose transporter function. Journal of immunology (Baltimore, Md. : 1950) 44 8666774
1995 APO-1(CD95)-mediated apoptosis in Jurkat cells does not involve src kinases or CD45. FEBS letters 44 7543423
1997 Anti-Fas IgG1 antibodies recognizing the same epitope of Fas/APO-1 mediate different biological effects in vitro. International immunology 41 9040002
1996 Soluble Fas/Apo-1 splicing variants and apoptosis. Frontiers in bioscience : a journal and virtual library 41 9159204
1999 Regulation of CD95 (Apo-1/Fas) ligand and receptor expression in squamous-cell carcinoma by interferon-gamma and cisplatin. International journal of cancer 40 9935158
1998 The role of p53 and the CD95 (APO-1/Fas) death system in chemotherapy-induced apoptosis. European cytokine network 40 9889415
1997 Fas (CD95, APO-1) antigen expression and function in murine mast cells. Journal of immunology (Baltimore, Md. : 1950) 39 9378990
1998 Differential regulation of CD95 (Fas/APO-1) expression in human blood eosinophils. European journal of immunology 38 9692873
1997 Expression of fas (CD95/APO-1) antigen induced by radiation therapy for diffuse B-cell lymphoma: immunohistochemical study. Clinical cancer research : an official journal of the American Association for Cancer Research 38 9815617
2009 Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family. Biochemical and biophysical research communications 37 19615968

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