Affinage

FADD

FAS-associated death domain protein · UniProt Q13158

Length
208 aa
Mass
23.3 kDa
Annotated
2026-04-28
100 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FADD is a central adaptor protein in extrinsic cell death signaling that bridges death receptors to downstream effector caspases and simultaneously serves as a critical checkpoint suppressing necroptosis and regulating NF-κB activation, cell cycle progression, and innate immune signaling. Through its C-terminal death domain (DD), FADD binds the cytoplasmic domains of Fas, TRADD (downstream of TNFR1), DR4, and DR5 to nucleate the death-inducing signaling complex (DISC), while its N-terminal death effector domain (DED) recruits procaspase-8, procaspase-10, and cFLIP via surface-specific interactions that determine whether the outcome is apoptosis, survival-associated NF-κB signaling via the RIPK1-containing FADDosome, or suppression of RIPK3/MLKL-dependent necroptosis (PMID:7538907, PMID:8681376, PMID:19118384, PMID:38710704, PMID:37988267). Genetic ablation of FADD in intestinal epithelial cells, keratinocytes, T lymphocytes, or whole embryos unleashes RIP3-dependent necroptosis and, in some contexts, ZBP1- and GSDMD-dependent inflammatory cell death, all of which are rescued by concurrent RIPK3 deletion (PMID:21804564, PMID:22000287, PMID:21368761, PMID:32362323, PMID:36191211). FADD phosphorylation at Ser194 by CK1α localizes FADD to mitotic spindle poles and regulates G2/M progression and RAS-driven tumorigenesis, while SUMOylation at K120/125/149 redirects FADD to mitochondria where it promotes Drp1-dependent necrosis, and K6-linked polyubiquitylation by CHIP at K149/153 suppresses DISC assembly (PMID:16061179, PMID:25628462, PMID:27799292, PMID:29795330).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1995 High

    Before FADD's discovery, how Fas transduced its death signal was unknown; identification of FADD as a DD-containing adaptor that binds Fas and induces CrmA-sensitive apoptosis established the first proximal signal transducer in the extrinsic death pathway.

    Evidence Yeast two-hybrid screen, overexpression in MCF7/BJAB cells, dominant-negative mutagenesis

    PMID:7538907

    Open questions at the time
    • The downstream effector protease was not yet identified
    • FADD's mechanism of inducing apoptosis was unclear
  2. 1996 High

    The identity of the enzyme recruited by FADD was resolved when caspase-8 (MACH/FLICE) was cloned as a DED-mediated FADD interactor, and FADD was shown to link both Fas and TNFR1 (via TRADD) to caspase activation, establishing the DISC concept and bifurcation of TNFR1 signaling into apoptosis (TRADD-FADD) versus NF-κB (TRADD-TRAF2).

    Evidence Protein interaction cloning for caspase-8, Co-IP and dominant-negative epistasis for TRADD-FADD versus TRADD-TRAF2 pathways

    PMID:8565075 PMID:8681376

    Open questions at the time
    • Structural basis of DED-DED interaction unknown
    • Whether FADD is required for all death receptors was untested
  3. 1997 High

    Extension of FADD's role to the TRAIL pathway was established when DR4 and DR5 were shown to directly bind FADD and require it for death signaling.

    Evidence Co-IP of DR4/DR5 with FADD, dominant-negative FADD blockade of TRAIL-induced death

    PMID:9430228

    Open questions at the time
    • Whether FADD is recruited directly or via TRADD to TRAIL receptors was debated
  4. 1998 High

    Multiple lines of evidence in 1998 redefined FADD from a pure death adaptor to a pleiotropic signaling node: the DED structure was solved revealing the hydrophobic surface for caspase-8 binding; FADD-null embryos died at E11.5 with cardiac failure (indicating non-apoptotic roles); FADD-DN transgenic mice showed impaired T cell development and proliferation; and FADD was required for PKR-dependent apoptosis.

    Evidence NMR structure with mutagenesis; FADD-knockout mice; FADD-DN transgenic mice with T cell assays; FADD-deficient fibroblasts with dsRNA/PKR

    PMID:9450996 PMID:9506948 PMID:9582077 PMID:9586634 PMID:9843495

    Open questions at the time
    • Mechanism of FADD's pro-survival/proliferative role in T cells was unknown
    • Identity of the kinase phosphorylating FADD was uncertain
    • Whether cardiac lethality was cell-autonomous was not determined
  5. 2000 High

    Endogenous DISC biochemistry was clarified: TRAIL recruits endogenous FADD and caspase-8 directly (without TRADD/RIP) to DR4/DR5 complexes, and FADD-null MEFs confirmed absolute FADD dependence for TRAIL killing; separately, FADD was shown to activate NF-κB through a caspase-8 scaffolding (non-catalytic) pathway requiring RIP and NIK.

    Evidence Endogenous Co-IP without overexpression for TRAIL-DISC; FADD-null MEFs with DR4/DR5 stable expression and FADD rescue; overexpression epistasis with catalytically inactive caspase-8, dominant-negative RIP/NIK

    PMID:10753878 PMID:10862756 PMID:10894161

    Open questions at the time
    • Stoichiometry and architecture of the native DISC were not resolved
    • Whether NF-κB activation by FADD is physiologically relevant in vivo was untested
  6. 2004 High

    FADD's NF-κB role was confirmed at endogenous levels downstream of Fas, requiring RIP and the scaffolding function of caspase-8 with FLIP as a negative regulator, while FADD was observed to aggregate into cap structures during T cell mitogenic stimulation, hinting at context-dependent signaling platforms.

    Evidence Co-IP with endogenous proteins, catalytically inactive caspase-8 mutant, siRNA against FLIP; confocal microscopy and subcellular fractionation in stimulated T cells

    PMID:15017386 PMID:15289496

    Open questions at the time
    • The post-translational modification of FADD during mitogenic stimulation was not biochemically identified
  7. 2005 High

    The kinase responsible for FADD Ser194 phosphorylation was identified as CK1α; phospho-FADD colocalizes with CK1α at mitotic spindle poles, linking FADD to cell cycle regulation beyond death signaling.

    Evidence In vitro kinase assay with CK1α, in vivo phosphorylation, immunofluorescence colocalization, CK1 pharmacological inhibition

    PMID:16061179

    Open questions at the time
    • Downstream targets of phospho-FADD at the spindle were not identified
    • How phospho-FADD mechanistically promotes mitotic arrest was unclear
  8. 2006 High

    The full-length FADD NMR structure revealed an orthogonal DED-DD arrangement with defined interaction surfaces for Fas-DD and procaspase-8 prodomain, and identified a DED hydrophobic patch mediating FADD self-association essential for DISC nucleation.

    Evidence NMR structure of full-length FADD, mutagenesis of interaction surfaces, functional reconstitution

    PMID:16762833

    Open questions at the time
    • Higher-order oligomeric DISC architecture remained unresolved
  9. 2007 High

    FADD's roles expanded to include negative regulation of TLR4 signaling (via IRAK1/MyD88 interaction) and intrinsic apoptosis (via AK2-FADD-caspase-10 complex), while phosphomimetic FADD knock-in mice revealed that constitutive Ser191 phosphorylation impairs G0/G1-to-S transition by disrupting CDK2/Rb/p27 regulation.

    Evidence Endogenous Co-IP of FADD-IRAK1-MyD88, FADD-null cells for TLR hyperactivation; AK2 reconstitution with caspase-10 in cell-free system; FADD-D phosphomimetic knock-in mice with cell cycle analysis

    PMID:17553783 PMID:17785432 PMID:17952061

    Open questions at the time
    • The physiological significance of AK2-FADD-caspase-10 in vivo was not established
    • Whether FADD's TLR-regulatory role operates in vivo was not tested
  10. 2008 High

    The crystal structure of the Fas-FADD DD complex revealed a tetrameric assembly (4 Fas DD : 4 FADD DD) with a conformational opening mechanism that prevents accidental DISC assembly and enables processive clustering upon sufficient ligand stimulus.

    Evidence X-ray crystallography at 2.7 Å resolution

    PMID:19118384

    Open questions at the time
    • Full DISC architecture including DED filament was not captured
    • How the tetramer transitions to productive signaling was modeled but not directly observed
  11. 2010 High

    FADD was established as a negative regulator of necroptosis: conditional FADD-KO T cells underwent RIP1-dependent programmed necrosis upon TCR stimulation, rescued by necrostatin-1, redefining FADD as a guardian against necroptotic death.

    Evidence T-cell-specific conditional FADD KO, necrostatin-1 rescue, proliferation assays

    PMID:20615958

    Open questions at the time
    • Whether the necroptosis-suppressive role requires caspase-8 catalytic activity or FADD scaffolding was not distinguished
    • RIP3 involvement was not directly tested
  12. 2011 High

    Compound genetic studies definitively established FADD as the central checkpoint preventing RIPK3-mediated necroptosis across tissues: FADD deletion in intestinal epithelium or keratinocytes caused RIP3-dependent necrosis and inflammation rescued by RIP3 KO; FADD/RIP1 double-KO rescued embryonic lethality, demonstrating that FADD-null lethality is driven by unrestrained RIP1 signaling.

    Evidence IEC-specific and keratinocyte-specific FADD conditional KOs crossed with RIP3-KO, CYLD-KO, and TNF pathway mutants; FADD/RIP1 double-KO embryos

    PMID:21368761 PMID:21804564 PMID:22000287

    Open questions at the time
    • ZBP1 contribution was not yet appreciated
    • Whether necroptosis or secondary inflammation drives pathology was not fully dissected
  13. 2012 High

    The FADD-caspase-8-cFLIPL heterocomplex was shown to have a distinct survival function that suppresses RIPK3-dependent necroptosis while cFLIPL simultaneously prevents FADD-caspase-8-driven apoptosis, as demonstrated by triple-KO genetic epistasis.

    Evidence FADD/RIPK3, cFLIP/RIPK3, and FADD/cFLIP/RIPK3 compound KO mouse genetics with embryonic viability analysis

    PMID:22675671

    Open questions at the time
    • How enzymatic activity of the heterodimer is regulated to suppress necroptosis but not kill was unclear
  14. 2013 High

    IFN-induced necroptosis was found to require FADD inactivation (via Ser191 phosphorylation) and caspase suppression; PKR was identified as the IFN-induced kinase bridging to RIP1 necrosome assembly, placing FADD phosphorylation as a physiological switch from apoptosis suppression to necroptosis permissiveness.

    Evidence FADD-deficient cells, phosphorylation mutants (S191), PKR-RIP1 Co-IP, Jak/STAT inhibition

    PMID:23898178

    Open questions at the time
    • Whether phospho-FADD is actively pro-necroptotic or merely non-functional was not resolved
  15. 2014 High

    Surface-specific DED interactions were mapped: FLIP preferentially binds FADD's α1/α4 surface while procaspase-8 binds α2/α5, explaining how FADD nucleates a defined DISC stoichiometry that determines cell fate.

    Evidence Structure-guided mutagenesis of DED surfaces, DISC stoichiometry analysis, functional apoptosis assays

    PMID:24577104

    Open questions at the time
    • Atomic-resolution ternary structure was not yet available
    • How stoichiometry shifts between apoptosis and survival was not quantitatively modeled
  16. 2015 High

    Phospho-FADD was linked to oncogenesis: CK1α-dependent Ser194 phosphorylation downstream of KRAS(G12D) was required for lung tumorigenesis, and phospho-FADD interacted with mitotic kinases PLK1, AURKA, and BUB1, establishing a non-apoptotic tumor-promoting function.

    Evidence Conditional mouse lung cancer models, mass spectrometry interactome of phospho-FADD, CK1α conditional KO

    PMID:25628462

    Open questions at the time
    • Direct substrates or effectors of the phospho-FADD–mitotic kinase complexes were not identified
    • Generalizability beyond KRAS-driven lung cancer was untested
  17. 2017 High

    Post-translational regulation of FADD was expanded: SUMOylation at K120/125/149 redirects FADD to mitochondria where it promotes Drp1-dependent necrosis via caspase-10; bacterial NleB1 GlcNAcylates FADD Arg117 to block death receptor signaling during infection; and LUBAC attaches linear ubiquitin chains to FADD.

    Evidence SUMO modification mapping with mutants, mitochondrial fractionation, ternary complex reconstitution; mass spectrometry for arginine-GlcNAcylation during EPEC infection; in vitro ubiquitination assays for LUBAC

    PMID:27799292 PMID:28189684 PMID:28860194

    Open questions at the time
    • Physiological triggers of FADD SUMOylation beyond calcium ionophore were limited to ischemia
    • Whether linear ubiquitylation of FADD regulates DISC in vivo was not shown
  18. 2018 High

    CHIP E3 ligase was identified as mediating K6-linked polyubiquitylation of FADD at K149/K153, which prevents DISC formation; CHIP depletion sensitized cells to FasL/TRAIL, defining a ubiquitin-dependent brake on death receptor signaling.

    Evidence Mass spectrometry for ubiquitin linkage and site, mutagenesis, siRNA depletion, DISC assembly assays, xenograft models

    PMID:29795330

    Open questions at the time
    • Deubiquitinase opposing CHIP on FADD was not identified
    • Interplay between K6-Ub and SUMO modifications at overlapping lysines was unexplored
  19. 2020 High

    The full scope of FADD's checkpoint role was clarified: in IECs, FADD loss triggers both MLKL-mediated necroptosis (via ZBP1 and TNFR1-RIPK1/RIPK3) and caspase-8/GSDMD-dependent pyroptosis-like death; the RIPK1-caspase-8-FADD 'FADDosome' was defined as a distinct NF-κB-activating complex whose dosage determines inflammatory outcomes in vivo.

    Evidence IEC-specific compound conditional KOs (FADD, caspase-8, MLKL, GSDMD, ZBP1); Casp8D387A knock-in with Mlkl-/- and Fadd heterozygosity

    PMID:32362323 PMID:32428502

    Open questions at the time
    • How FADD distinguishes DISC (apoptotic) from FADDosome (inflammatory) assembly in the same cell was mechanistically unclear
  20. 2022 High

    A cGAS-STING-TBK1 positive feedback loop was found to drive ZBP1 upregulation upon FADD or caspase-8 loss, explaining how FADD deficiency licenses spontaneous necroptosis through innate immune sensing.

    Evidence FADD/caspase-8-deficient cells, ZBP1 KO rescue, FLAG-MLKL reporter mice, cGAS/STING pathway inhibition

    PMID:36191211

    Open questions at the time
    • What nucleic acid species activates cGAS-STING upon FADD loss was not identified
    • Whether this feedback operates in all FADD-deficient tissues was untested
  21. 2023 High

    The mechanism by which cFLIPL suppresses FADDosome-driven NF-κB was resolved: cFLIPL's low affinity for FADD increases its occupancy of FADDosome complexes, competitively displacing FADD/RIPK1 from caspase-8 and blocking inflammatory cytokine output.

    Evidence cFLIP KO/siRNA, FADDosome immunoprecipitation, NF-κB reporter, cytokine ELISA

    PMID:37988267

    Open questions at the time
    • Structural basis of differential FLIP affinity for DISC versus FADDosome was not determined
  22. 2024 High

    Atomic-resolution structures of the FADD-procaspase-8-cFLIP ternary DED complex by X-ray crystallography and cryo-EM revealed a helical hetero-double-layer architecture that limits caspase-8 activation for survival signaling, providing the structural basis for how FADD nucleates fate decisions.

    Evidence X-ray crystallography and cryo-EM of ternary complex, structure-guided mutagenesis, caspase-8 activation and necroptosis functional assays

    PMID:38710704

    Open questions at the time
    • Full-length DISC structure including transmembrane receptor and lipid bilayer context is still lacking
    • How the ternary complex transitions from survival to apoptotic mode in real time is not captured

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how FADD discriminates between DISC and FADDosome assembly in the same cell upon the same stimulus; the structural basis of phospho-FADD function at mitotic spindle poles; whether FADD SUMOylation and K6-ubiquitylation at overlapping lysines are mutually regulated; and the identity of the endogenous nucleic acid ligand that activates cGAS-STING upon FADD loss to drive ZBP1-dependent necroptosis.
  • No full DISC structure in lipid bilayer context
  • Phospho-FADD mitotic substrates/effectors unknown
  • Cross-talk between SUMO and K6-Ub modifications uncharacterized
  • Endogenous cGAS-STING trigger in FADD-deficient cells unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 9
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-5357801 Programmed Cell Death 9 R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 1
Partners
CASP10CASP8CFLARCSNK1A1FASRIPK1STUB1TRADD
Complex memberships
AK2-FADD-caspase-10 (AFAC10)DISC (death-inducing signaling complex)FADD-caspase-8-cFLIPL heterocomplexFADDosome (RIPK1-caspase-8-FADD)

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 FADD (Fas-associated death domain protein) was identified as a novel protein that binds the cytoplasmic death domain of Fas via a homologous death domain, and overexpression of FADD induces apoptosis blocked by CrmA, placing FADD as a proximal signal transducer downstream of Fas. Yeast two-hybrid, overexpression in MCF7/BJAB cells, dominant-negative point mutation (analogous to lpr) abolishing Fas binding Cell High 7538907
1996 FADD (MORT1) recruits MACH (caspase-8/caspase-10 homolog) through a death effector domain interaction; proteolytic MACH isoforms induce cell death, making MACH the most upstream enzymatic component in Fas/APO-1- and p55-TNF-R-induced death cascades downstream of FADD. Protein interaction cloning, overexpression of isoforms, dominant-negative inhibition of Fas/TNF-R cytotoxicity Cell High 8681376
1996 TRADD directly interacts with both TRAF2 and FADD, defining two distinct TNFR1 signaling cascades: TRADD-TRAF2 activates NF-κB, and TRADD-FADD induces apoptosis. A dominant-negative FADD mutant lacking its N-terminal 79 amino acids selectively blocks TNF-induced apoptosis without affecting NF-κB activation. Co-immunoprecipitation, dominant-negative mutants, NF-κB reporter assays, apoptosis assays Cell High 8565075
1997 TRAIL receptors DR4 and DR5 directly bind FADD and TRADD as adaptor molecules; death signaling through both receptors is blocked by a dominant-negative form of FADD and by FLIP, and both receptors activate NF-κB. Co-immunoprecipitation, dominant-negative FADD inhibition, NF-κB reporter assays Immunity High 9430228
1998 NMR solution structure of the FADD death effector domain (DED) reveals a six-antiparallel-helix bundle similar to death domains; mutagenesis showed that a hydrophobic region unique to the DED (absent from death domains) is critical for binding FLICE/caspase-8 and apoptotic activity, while Fas-DD mutations have no effect on DED function. NMR structure determination (biologically active mutant), site-directed mutagenesis, functional apoptosis assays Nature High 9582077
1998 FADD is essential for apoptosis induced by CD95, TNFR-1, and DR3 in mouse embryonic fibroblasts, but not for apoptosis triggered by DR4, E1A, c-myc, or adriamycin. FADD-null mice die by embryonic day 11.5 with cardiac failure and hemorrhage, demonstrating a non-apoptotic developmental role. FADD gene knockout mice (loss-of-function), embryonic fibroblast apoptosis assays, chimeric embryo analysis Science High 9506948
1998 In transgenic mice expressing dominant-negative FADD (FADD-DN), early thymocyte development was impaired and peripheral T cell pools were depleted, indicating FADD plays a role in T cell development and activation beyond death-receptor-induced apoptosis. Transgenic mice expressing FADD-DN, T cell development assays, signaling analyses Immunity High 9586634
1998 FADD-DN transgenic mice showed enhanced negative selection of autoreactive thymocytes and inhibited T cell activation-induced proliferation; under certain circumstances FADD signaling promotes cell survival and proliferation rather than cell death. Transgenic mice expressing dominant-negative FADD, thymocyte selection assays, T cell activation assays The EMBO Journal High 9450996
1998 PKR-induced apoptosis by dsRNA requires FADD: murine fibroblasts lacking FADD were almost completely resistant to dsRNA-mediated cell death, placing FADD downstream of PKR activation in the death receptor-mediated apoptosis pathway. FADD-deficient fibroblasts, tetracycline-inducible PKR cell lines, dsRNA treatment, apoptosis assays The EMBO Journal High 9843495
1998 Kinases that associate with the membrane-proximal (non-death-domain) cytoplasmic region of Fas phosphorylate FADD/MORT1, suggesting FADD is a substrate for Fas-associated kinases distinct from the death domain interaction. GST fusion pulldown of Fas cytoplasmic domain, in vitro kinase assays, phosphorylation of FADD Journal of Immunology Medium 9590235
1998 TRADD and FADD signal activation of acid sphingomyelinase downstream of the p55 TNF receptor; TRAF2 and RIP, which activate NF-κB, do not affect A-SMase activation; caspase inhibitors reduce A-SMase activity, suggesting caspase involvement downstream of FADD. Overexpression in 293 cells, enzymatic A-SMase activity assay, caspase inhibitors The Journal of Biological Chemistry Medium 9488730
1999 Detachment-induced apoptosis (anoikis) is blocked by dominant-negative FADD in untransformed epithelial cells, and detachment induces strong caspase-8 activation upstream of caspase-3, in a manner independent of soluble death receptor ligands (CD95, DR4, DR5). Dominant-negative FADD overexpression, soluble receptor domain blocking, caspase activity assays, epithelial cell lines Current Biology High 10508619
2000 Apo2L/TRAIL stimulates formation of homomeric DR4/DR5 and heteromeric DR4-DR5 complexes and directly recruits endogenous FADD and caspase-8 (without TRADD or RIP) to activate caspase-8, using a mechanism similar to FasL/Fas signaling. Co-immunoprecipitation of endogenous proteins in non-transfected cells, caspase-8 activity assay Immunity High 10894161
2000 FADD is required for DR4- and DR5-mediated apoptosis by TRAIL: FADD-/- MEFs stably expressing TRAIL receptors are completely resistant to TRAIL-induced death, and re-introduction of FADD restores sensitivity. FADD-/- MEFs with stable receptor transfection, retroviral FADD reconstitution, apoptosis assays The Journal of Biological Chemistry High 10862756
2000 FADD overexpression potently activates NF-κB through a pathway requiring caspase-8 (but not its catalytic activity), TRAF2, NIK, IKKα, and IKKβ; RIP dominant-negative inhibits FADD-induced but not Casper-induced NF-κB; activated caspase-8 proteolytically inactivates NIK to negatively regulate NF-κB. Overexpression, caspase inhibitors (CrmA, BD-fmk), dominant-negative kinase mutants, NF-κB reporter, NIK cleavage by caspase-8 The Journal of Biological Chemistry High 10753878
2004 Fas activates NF-κB via a pathway requiring RIP, FADD, and caspase-8 scaffolding function (catalytic activity dispensable); endogenous FLIP isoforms negatively regulate Fas-induced NF-κB activation. Co-immunoprecipitation, dominant-negative mutants, caspase-inactive point mutants, siRNA knockdown, NF-κB reporter assays The Journal of Cell Biology High 15289496
2005 Casein kinase Iα (CKIα) phosphorylates FADD at Ser194 both in vitro and in vivo; FADD-CKIα association regulates FADD subcellular localization; phosphorylated FADD colocalizes with CKIα at spindle poles in metaphase; CKI inhibition prevents Taxol-mediated mitotic arrest and blocks mitogen-induced proliferation. In vitro kinase assay with CKIα, in vivo phosphorylation, immunofluorescence co-localization, pharmacological CKI inhibition, FADD phosphorylation-site mutant mice Molecular Cell High 16061179
2006 The full FADD structure was solved by NMR, revealing DED and DD in orthogonal tail-to-tail arrangement; mutagenesis defined interaction surfaces for CD95 intracellular domain and procaspase-8 prodomain; a hydrophobic patch around F25 in the DED mediates FADD self-association; the FADD DED preferentially contacts one DED of procaspase-8 perpendicularly. NMR structure, mutagenesis, functional reconstitution with binding partners Molecular Cell High 16762833
2007 Mitochondrial AK2 forms a ternary AFAC10 complex with FADD and caspase-10 during intrinsic apoptosis; AK2 translocates to cytoplasm upon intrinsic apoptotic signals and promotes FADD-caspase-10 association and caspase-10 activation (but not caspase-8), subsequently activating caspase-3. Co-immunoprecipitation, siRNA knockdown, cell-free caspase activation assay with purified AK2, confocal microscopy of AK2 translocation Nature Cell Biology High 17952061
2007 FADD negatively regulates TLR4/LPS signaling by interacting with IRAK1 and MyD88; LPS stimulation increases IRAK1-FADD interaction and recruitment of the IRAK1-FADD complex to MyD88; FADD-null cells show hyperactivation of JNK and PI3K; FADD requires IRAK1 to interact with MyD88. Co-immunoprecipitation of endogenous proteins, FADD-null cells, IRAK1-null cells, forced expression, cytokine production assays Molecular and Cellular Biology High 17785432
2008 Crystal structure of the human Fas-FADD death domain complex at 2.7 Å reveals a tetrameric arrangement of four FADD DDs bound to four Fas DDs; an opening of the Fas DD exposes the FADD binding site and generates a Fas-Fas bridge, forming a regulatory complex that prevents accidental DISC assembly while allowing processive DISC clustering upon sufficient stimulus. X-ray crystallography (2.7 Å), isolation and characterization of the human Fas-FADD DD complex Nature High 19118384
2010 FADD functions as a negative regulator of TCR-induced necroptosis in T cells; conditional FADD-KO T cells respond poorly to TCR triggering and exhibit amplified RIP1-dependent programmed necrosis; inhibition of RIP1 kinase activity rescues the FADD-KO proliferative defect. Conditional T-cell-specific FADD knockout, TCR stimulation, RIP1 kinase inhibitor (necrostatin), proliferation assays PNAS High 20615958
2010 FADD interacts with TRIM21; together they suppress IFN-α production by ubiquitinating IRF7, affecting its phosphorylation, and interfering with TRAF6 ubiquitin ligase activity; FADD-TRIM21 interaction enhances TRIM21 E3 ligase activity. Co-immunoprecipitation, ubiquitination assays, IRF7 phosphorylation, Sendai virus infection, siRNA knockdown, virus titer measurement The Journal of Biological Chemistry High 21183682
2011 FADD prevents RIP3-mediated epithelial cell necrosis in the intestine; IEC-specific FADD-KO mice develop spontaneous epithelial necrosis, Paneth cell loss, and colitis that is genetically prevented by RIP3 deficiency; CYLD deubiquitinase and TNF signaling contribute to RIP3-dependent necrosis in the colon. IEC-specific conditional KO mice, RIP3 double-KO, CYLD conditional KO, TNF/MYD88 deficiency crosses, histological and genetic epistasis analysis Nature High 21804564
2011 FADD deficiency in keratinocytes induces RIP3-mediated necroptosis (necroptosis) and skin inflammation; genetic ablation of RIP3 prevents inflammatory skin lesions in FADD(E-KO) mice; CYLD deubiquitinase and TNF-TNFR1 signaling contribute partly to keratinocyte necroptosis. Keratinocyte-specific conditional FADD KO, RIP3 double-KO epistasis, CYLD conditional KO, TNF pathway analysis Immunity High 22000287
2011 FADD deficiency causes embryonic lethality accompanied by massive necrosis and elevated RIP1; RIP1 deficiency rescues normal embryogenesis of FADD-/- mice; conversely, FADD deletion partially corrects RIP1-/- lymphocyte developmental defects; RIP1 deficiency fully restores normal T cell (but not B cell) proliferation in FADD-/- mice, revealing a cell-type-specific interplay between FADD and RIP1. FADD/RIP1 double-knockout mice, embryonic viability assays, lymphocyte proliferation, apoptosis assays with Fas/TNF-α Nature High 21368761
2012 The FADD-caspase-8-cFLIPL complex has a survival function: FADD/RIPK3 double-KO mice develop normally, but lethality of cFLIP-null mice is not rescued by RIPK3 ablation; in FADD/cFLIP/RIPK3 triple-KO mice embryonic development is normal, showing the FADD-caspase-8-cFLIPL enzymatic complex blocks RIPK3-dependent signaling while cFLIPL blocks RIPK3-independent apoptosis by the FADD-caspase-8 complex. FADD/RIPK3, cFLIP/RIPK3, and FADD/cFLIP/RIPK3 compound KO mouse genetics, embryonic viability analysis Cell Reports High 22675671
2013 IFN-induced necrosis via RIP1/RIP3 necrosome assembly requires FADD to be lost or disabled; FADD phosphorylation on Ser191 disables FADD and collaborates with caspase inactivation to allow IFN-activated necrosis; IFNs transcriptionally activate PKR, which interacts with RIP1 to initiate necrosome formation; FADD and caspases act as negative regulators of this IFN-induced necroptosis. FADD-deficient cells, FADD phosphorylation mutant (S191), Jak1/STAT1 inhibition, PKR-RIP1 Co-IP, necrosome assembly assays PNAS High 23898178
2014 FLIP has preferential affinity for the α1/α4 surface of the FADD DED, whereas procaspase-8 preferentially binds the α2/α5 surface; following death receptor recruitment, FADD DED preferentially engages FLIP via α1/α4 and procaspase-8 via α2/α5, with tripartite FLIP/FADD/procaspase-8 intermediates forming via FLIP DED1 α1/α4 and procaspase-8 DED2 α2/α5. Mutagenesis of FADD/FLIP/procaspase-8 DED surfaces, DISC stoichiometry analysis, functional apoptosis assays Nature Communications High 24577104
2015 CK1α phosphorylates FADD downstream of RAS, and KRAS(G12D)-driven lung cancer requires both FADD and its phosphorylation by CK1α; phosphorylated FADD interacts with mitotic kinases PLK1, AURKA, and BUB1 at G2/M; CK1α deletion abrogates FADD phosphorylation and suppresses lung cancer development. Conditional mouse models, immunohistochemistry, in vivo imaging, mass spectrometry of phospho-FADD interactome, CK1α inhibitor Science Signaling High 25628462
2017 The bacterial effector NleB1 modifies Arg117 of FADD with N-acetylglucosamine (GlcNAc) as an arginine glycosyltransferase, irreversibly blocking death-receptor-induced apoptosis; during EPEC and C. rodentium infection, FADD is the preferred substrate for NleB1-mediated GlcNAcylation. Affinity proteomics for arginine-GlcNAcylated glycopeptides, EPEC/C. rodentium infection (in vitro and in vivo), mass spectrometry, apoptosis assays The Journal of Biological Chemistry High 28860194
2017 FADD is SUMOylated at K120/125/149 by SUMO2 during necrosis caused by calcium ionophore A23187 or ischemia; SUMOylated FADD binds Drp1 to promote its mitochondrial recruitment via Mff, driving mitochondrial fragmentation and necrosis; caspase-10 (but not caspase-8) forms a ternary complex with SUMO-FADD/Drp1 on mitochondria, potentiating Drp1 oligomerization. SUMO modification mapping, FADD SUMO-defective mutants, Co-IP in cells and ischemic tissue, mitochondrial fractionation, in vitro binding Molecular and Cellular Biology High 27799292
2018 CHIP E3 ubiquitin ligase mediates K6-linked polyubiquitylation of FADD at Lys149 and Lys153, preventing DISC formation and suppressing cell death; CHIP-depleted cells show enhanced sensitivity to FasL and TRAIL with increased DISC assembly; FADD mutated at K149/153 cannot be suppressed by CHIP. Co-immunoprecipitation, ubiquitination assays, mass spectrometry identification of ubiquitination sites, siRNA depletion, xenograft assays Oncogene High 29795330
2019 NLRP3 inflammasome activation induces unconventional secretion of FADD through microvesicle shedding in human monocytes/macrophages; this FADD secretion requires K+ efflux, NLRP3 sensor, ASC adaptor, and caspase-1, and is distinct from IL-1β release and pyroptosis. Pharmacological NLRP3 activation, K+ efflux assays, siRNA knockdown of NLRP3 components, microvesicle isolation, proteomics Cell Death & Disease Medium 30804327
2020 FADD and caspase-8 act in IECs to prevent intestinal inflammation by inhibiting ZBP1- and TNFR1-mediated RIPK1/RIPK3 signaling; IEC FADD deficiency causes MLKL-mediated necroptosis and also caspase-8/GSDMD-dependent pyroptosis-like death, with both pathways contributing to ileitis. IEC-specific conditional KO for FADD, caspase-8, MLKL, GSDMD; compound genetic epistasis, histological analysis Immunity High 32362323
2020 The RIPK1-caspase-8-FADD (FADDosome) complex mediates NF-κB-driven inflammation in vivo; double-KO studies showed that removal of one allele of Fasl, Fadd, or Ripk1 prevented pathology in Casp8D387A/D387A Mlkl-/- mice; complete FADD ablation revealed a FADD-independent inflammatory role of caspase-8 involving an inflammasome. Compound conditional KO mice (Caspase-8 mutant, Mlkl-/-, Fadd-/-, Ripk1 heterozygous), in vivo pathology analysis Immunity High 32428502
2022 Caspase-8 and FADD suppress spontaneous ZBP1 expression and ZBP1-dependent necroptosis; FADD- or caspase-8-deficient cells show increased ZBP1 expression, leading to spontaneous RIPK3 activation and MLKL phosphorylation; this ZBP1 upregulation relies on a cGAS-STING-TBK1 positive feedback mechanism. Caspase-8/FADD-deficient cells, ZBP1 KO in Casp8-/- mice, FLAG-tagged MLKL knock-in reporter mice, cGAS/STING pathway inhibition, ZBP1 reconstitution PNAS High 36191211
2023 cFLIPL suppresses Fas- and TRAIL-initiated NF-κB activation by inhibiting assembly of caspase-8/FADD/RIPK1 FADDosome complexes; cFLIPL's low affinity for FADD causes increased cFLIPL occupancy of FADDosomes to diminish FADD/RIPK1 recruitment to caspase-8, thereby blocking NF-κB and inflammatory cytokine production. cFLIP siRNA/KO, FADDosome complex immunoprecipitation, NF-κB reporter, cytokine ELISA, FADD/RIPK1 interaction assays Cell Reports High 37988267
2024 X-ray crystallography and cryo-EM structures of human FADD-procaspase-8-cFLIP ternary DED complexes reveal how FADD and cFLIP orchestrate assembly; a helical procaspase-8-cFLIP hetero-double layer promotes limited caspase-8 activation for cell survival; structure-guided mutagenesis confirmed roles in caspase-8 activation and RIPK1 regulation. X-ray crystallography, cryo-EM structure determination, structure-guided mutagenesis, functional caspase-8 activation and necroptosis assays Nature Communications High 38710704
2017 HOIP (LUBAC subunit) is cleaved by caspases during apoptosis, decreasing linear ubiquitination of FADD (and NEMO); FADD is identified as a substrate for LUBAC-mediated linear ubiquitin chain attachment. In vitro and cell-based ubiquitination assays, HOIP cleavage mapping, Co-IP Biochemical and Biophysical Research Communications Medium 28189684
2007 Constitutive phosphorylation of FADD at Ser191 (phosphomimetic FADD-D mutant) causes defective G0/G1-to-S transition with abnormalities in p130, p27 degradation, Rb phosphorylation, CDK2 activity, and FoxM1 upregulation; phosphomimetic FADD is also mislocalized during cell cycle progression. FADD-D knock-in mice, flow cytometric cell cycle analysis, biochemical analysis of cell cycle regulators, localization studies The Journal of Biological Chemistry High 17553783
2004 During T lymphocyte stimulation, FADD and caspase-8 aggregate in multiprotein complexes and form caps at the plasma membrane; mitogenic stimulation (but not Fas ligation) induces a unique post-translational modification of FADD, potentially determining whether FADD promotes death or proliferation. Novel monoclonal antibodies, confocal microscopy, subcellular fractionation, Co-IP during apoptosis and mitogenic activation Cell Death and Differentiation Medium 15017386

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 2096 7538907
1996 Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 2048 8681376
1996 TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 1708 8565075
2000 Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 817 10894161
1998 FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science (New York, N.Y.) 761 9506948
1997 TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity 598 9430228
2011 FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 511 21804564
1998 A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. The EMBO journal 362 9450996
2011 Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature 360 21368761
1997 Casper is a FADD- and caspase-related inducer of apoptosis. Immunity 339 9208847
1998 Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling. The EMBO journal 315 9843495
2013 Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proceedings of the National Academy of Sciences of the United States of America 300 23898178
2008 The Fas-FADD death domain complex structure unravels signalling by receptor clustering. Nature 299 19118384
2012 Survival function of the FADD-CASPASE-8-cFLIP(L) complex. Cell reports 281 22675671
1999 Fas ligand-independent, FADD-mediated activation of the Fas death pathway by anticancer drugs. The Journal of biological chemistry 277 10075697
2011 The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation. Immunity 251 22000287
2000 Activation of NF-kappaB by FADD, Casper, and caspase-8. The Journal of biological chemistry 244 10753878
2015 MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD. Circulation research 234 26038570
2020 FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells. Immunity 229 32362323
2004 NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP. The Journal of cell biology 210 15289496
1998 NMR structure and mutagenesis of the FADD (Mort1) death-effector domain. Nature 205 9582077
1998 A role for FADD in T cell activation and development. Immunity 201 9586634
2017 Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates. Nature medicine 190 28218919
1999 Involvement of FADD and caspase-8 signalling in detachment-induced apoptosis. Current biology : CB 189 10508619
2000 FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts. The Journal of biological chemistry 188 10862756
2010 FADD: a regulator of life and death. Trends in immunology 160 20576468
1999 FADD is required for multiple signaling events downstream of the receptor Fas. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 157 10616904
2006 The structure of FADD and its mode of interaction with procaspase-8. Molecular cell 152 16762833
2010 Whole-exome-sequencing-based discovery of human FADD deficiency. American journal of human genetics 144 21109225
1998 TNF receptor death domain-associated proteins TRADD and FADD signal activation of acid sphingomyelinase. The Journal of biological chemistry 137 9488730
2010 Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proceedings of the National Academy of Sciences of the United States of America 129 20615958
2005 Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities. Molecular cell 129 16061179
2020 AFP promotes HCC progression by suppressing the HuR-mediated Fas/FADD apoptotic pathway. Cell death & disease 126 33009373
2020 Caspase-8-Dependent Inflammatory Responses Are Controlled by Its Adaptor, FADD, and Necroptosis. Immunity 124 32428502
2000 FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor. The EMBO journal 120 10698935
2005 Phosphorylated FADD induces NF-kappaB, perturbs cell cycle, and is associated with poor outcome in lung adenocarcinomas. Proceedings of the National Academy of Sciences of the United States of America 117 16109772
2012 The roles of FADD in extrinsic apoptosis and necroptosis. BMB reports 110 23010170
2017 Long Noncoding RNA H19/miR-675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 104 28848149
2005 Nonapoptotic functions of FADD-binding death receptors and their signaling molecules. Current opinion in cell biology 103 16226446
1999 Improved artificial death switches based on caspases and FADD. Human gene therapy 100 10515447
2020 ATRX/EZH2 complex epigenetically regulates FADD/PARP1 axis, contributing to TMZ resistance in glioma. Theranostics 94 32194873
2011 Requirement of FADD, NEMO, and BAX/BAK for aberrant mitochondrial function in tumor necrosis factor alpha-induced necrosis. Molecular and cellular biology 93 21746883
2006 Prolonged activation of ERK1,2 induces FADD-independent caspase 8 activation and cell death. Apoptosis : an international journal on programmed cell death 79 16538383
2007 AK2 activates a novel apoptotic pathway through formation of a complex with FADD and caspase-10. Nature cell biology 78 17952061
2006 Morphine promotes Jurkat cell apoptosis through pro-apoptotic FADD/P53 and anti-apoptotic PI3K/Akt/NF-kappaB pathways. Journal of neuroimmunology 76 16529824
1999 FADD/MORT1, a signal transducer that can promote cell death or cell growth. The international journal of biochemistry & cell biology 73 10399313
2018 FADD at the Crossroads between Cancer and Inflammation. Trends in immunology 72 30401514
2014 Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces regulates DISC assembly. Nature communications 68 24577104
1997 Characterization of reaper- and FADD-induced apoptosis in a lepidopteran cell line. Molecular and cellular biology 63 9001220
2022 Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis. Proceedings of the National Academy of Sciences of the United States of America 62 36191211
2004 Phosphorylation of FADD is critical for sensitivity to anticancer drug-induced apoptosis. Carcinogenesis 62 15001534
2010 Fas-associated death domain (FADD) and the E3 ubiquitin-protein ligase TRIM21 interact to negatively regulate virus-induced interferon production. The Journal of biological chemistry 61 21183682
2010 Oligodendrocyte-specific FADD deletion protects mice from autoimmune-mediated demyelination. Journal of immunology (Baltimore, Md. : 1950) 60 21068410
2007 FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. Molecular and cellular biology 52 17785432
1998 FADD gene therapy for malignant gliomas in vitro and in vivo. Human gene therapy 52 9694158
2012 The adaptor protein FADD and the initiator caspase-8 mediate activation of NF-κB by TRAIL. Cell death & disease 47 23096115
2009 Curcumin induces apoptosis through FAS and FADD, in caspase-3-dependent and -independent pathways in the N18 mouse-rat hybrid retina ganglion cells. Oncology reports 46 19513510
2005 Nuclear localized phosphorylated FADD induces cell proliferation and is associated with aggressive lung cancer. Cell cycle (Georgetown, Tex.) 46 16258269
2017 The bacterial arginine glycosyltransferase effector NleB preferentially modifies Fas-associated death domain protein (FADD). The Journal of biological chemistry 45 28860194
2021 The lncRNA H19-Derived MicroRNA-675 Promotes Liver Necroptosis by Targeting FADD. Cancers 43 33499244
2016 FADD regulates NF-κB activation and promotes ubiquitination of cFLIPL to induce apoptosis. Scientific reports 43 26972597
2015 Phosphorylation of FADD by the kinase CK1α promotes KRASG12D-induced lung cancer. Science signaling 43 25628462
2008 Japanese encephalitis virus infection activates caspase-8 and -9 in a FADD-independent and mitochondrion-dependent manner. The Journal of general virology 43 18632964
2004 Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes. Cell death and differentiation 43 15017386
2004 FADD and its phosphorylation. IUBMB life 43 15545216
2017 RIPK3 Mediates Necroptosis during Embryonic Development and Postnatal Inflammation in Fadd-Deficient Mice. Cell reports 42 28445730
2000 Novel gene therapy for rheumatoid arthritis by FADD gene transfer: induction of apoptosis of rheumatoid synoviocytes but not chondrocytes. Gene therapy 42 10757027
2019 The classical NLRP3 inflammasome controls FADD unconventional secretion through microvesicle shedding. Cell death & disease 41 30804327
2017 RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice. Cell death and differentiation 40 28574501
1998 Phosphorylation of FADD/MORT1 and Fas by kinases that associate with the membrane-proximal cytoplasmic domain of Fas. Journal of immunology (Baltimore, Md. : 1950) 40 9590235
2019 FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications. Cancers 39 31569512
2016 A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death. The Journal of biological chemistry 39 27974463
2000 c-Jun NH2-terminal kinase activation leads to a FADD-dependent but Fas ligand-independent cell death in Jurkat T cells. The Journal of biological chemistry 38 11106658
2006 Molecular roles of MAP kinases and FADD phosphorylation in prostate cancer. Histology and histopathology 36 16437387
2021 TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection. Cellular and molecular neurobiology 35 33683530
2019 Diabetes induces IL-17A-Act1-FADD-dependent retinal endothelial cell death and capillary degeneration. Journal of diabetes and its complications 35 31239234
2023 cFLIPL acts as a suppressor of TRAIL- and Fas-initiated inflammation by inhibiting assembly of caspase-8/FADD/RIPK1 NF-κB-activating complexes. Cell reports 34 37988267
2022 FADD as a key molecular player in cancer progression. Molecular medicine (Cambridge, Mass.) 34 36348274
2018 K6 linked polyubiquitylation of FADD by CHIP prevents death inducing signaling complex formation suppressing cell death. Oncogene 34 29795330
2007 Constitutive phosphorylation mutation in Fas-associated death domain (FADD) results in early cell cycle defects. The Journal of biological chemistry 34 17553783
2010 Apigenin suppresses the growth of colorectal cancer xenografts via phosphorylation and up-regulated FADD expression. Oncology letters 33 22870126
2017 SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis. Molecular and cellular biology 32 27799292
2017 Decreased linear ubiquitination of NEMO and FADD on apoptosis with caspase-mediated cleavage of HOIP. Biochemical and biophysical research communications 32 28189684
2002 Identification of a basic surface area of the FADD death effector domain critical for apoptotic signaling. FEBS letters 31 12220669
2023 Ginsenoside Rb1 promotes the activation of PPARα pathway via inhibiting FADD to ameliorate heart failure. European journal of pharmacology 29 37001580
2004 Fas-associated protein with death domain (FADD)-independent recruitment of c-FLIPL to death receptor 5. The Journal of biological chemistry 29 15485835
2012 Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development. Human molecular genetics 27 22357656
2003 The CB1/VR1 agonist arvanil induces apoptosis through an FADD/caspase-8-dependent pathway. British journal of pharmacology 26 14530215
2010 The time course of unconditioned morphine-induced psychomotor sensitization mirrors the phosphorylation of FADD and MEK/ERK in rat striatum: role of PEA-15 as a FADD-ERK binding partner in striatal plasticity. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 24 19758790
2005 Recruitment of TRADD, FADD, and caspase 8 to double-stranded RNA-triggered death inducing signaling complexes (dsRNA-DISCs). Apoptosis : an international journal on programmed cell death 24 15711932
2003 Dominant negative MORT1/FADD rescues mice from CD95 and TNF-induced liver failure. Hepatology (Baltimore, Md.) 24 12500197
2017 FADD, Caspase-3, and Caspase-8 and Incidence of Coronary Events. Arteriosclerosis, thrombosis, and vascular biology 23 28302628
2024 Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis. Nature communications 22 38710704
2021 Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL. Cell death & disease 22 33976111
2017 The small molecule that packs a punch: ubiquitin-mediated regulation of RIPK1/FADD/caspase-8 complexes. Cell death and differentiation 22 28574505
2021 The cardioprotective effect of microRNA-103 inhibitor against isoprenaline-induced myocardial infarction in mice through targeting FADD/RIPK pathway. European review for medical and pharmacological sciences 21 33577038
2008 Changes in FADD levels, distribution, and phosphorylation in TNFalpha-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent. Apoptosis : an international journal on programmed cell death 21 18543108
2006 Signaling through the TRAIL receptor DR5/FADD pathway plays a role in the apoptosis associated with skeletal myoblast differentiation. Apoptosis : an international journal on programmed cell death 21 17041756
2022 DED Interaction of FADD and Caspase-8 in the Induction of Apoptotic Cell Death. Journal of microbiology and biotechnology 20 35879276
2021 The role of Fas-FasL-FADD signaling pathway in arsenic-mediated neuronal apoptosis in vivo and in vitro. Toxicology letters 20 34953944