Affinage

TRADD

Tumor necrosis factor receptor type 1-associated DEATH domain protein · UniProt Q15628

Length
312 aa
Mass
34.2 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRADD is the central death-domain adaptor of TNF receptor 1 (TNFR1) signaling, recruited to the activated receptor at the plasma membrane and nucleating two competing downstream branches: a TRAF2-dependent arm that activates NF-κB, JNK and MAPK survival/inflammatory programs, and a FADD-dependent arm that triggers caspase-8 apoptosis (PMID:7758105, PMID:8565075). Death-domain interactions assemble this signaling node — TRADD specifically engages the TNFR1 death domain and directly binds both TRAF2 and FADD, with the two effector pathways bifurcating at TRADD as defined by dominant-negative epistasis (PMID:8565075, PMID:8621670); structural work established a distinct TRADD–TRAF2 binding mode of higher affinity than direct receptor–TRAF2 contact, ensuring efficient TRAF2/cIAP recruitment (PMID:10892748, PMID:10911999). Genetic ablation in mice confirmed TRADD as the obligate organizer of the TNFR1 complex — required for TRAF2 recruitment, RIP1 ubiquitination, NF-κB/MAPK activation and apoptosis, and for TRIF-dependent TLR signaling, though partially dispensable in macrophages where abundant RIP1 compensates (PMID:18641654, PMID:18641653, PMID:18719121). TRADD competes with RIPK1 for TNFR1 recruitment, and this balance dictates whether NF-κB activation, caspase-8 apoptosis, or RIPK1-dependent necrosis is engaged (PMID:16611992); RIPK1 in turn restrains TRADD from forming the FADD–caspase-8 complex, so loss of RIPK1 unleashes TRADD-driven, TNFR1-independent apoptosis in vivo (PMID:30185824). Beyond TNFR1, TRADD is the shared adaptor for DR3/TL1A costimulation, TRAIL receptors, and p75NTR death-domain engagement (PMID:21421854, PMID:21187341, PMID:34175311), and it organizes a MAVS/Cardif antiviral complex with TRAF3, TANK, FADD and RIP1 to drive IRF3/NF-κB and type-I interferon responses (PMID:18439848). TRADD also shuttles into the nucleus, where it negatively regulates IFN-γ/STAT1 signaling (PMID:14730360), facilitates NHEJ DNA repair by recruiting 53BP1 and Ku70/Ku80 to double-strand breaks (PMID:28611389), and stabilizes p19Arf by modulating its ULF-mediated ubiquitination to enforce oncogene-induced senescence (PMID:22561347). Mechanistic control extends to autophagy and proteostasis: TRADD suppresses TRAF2/cIAP-mediated K63-ubiquitination of Beclin 1, and small molecules binding its N-terminal TRAF2-binding domain modulate ubiquitination of both RIPK1 and Beclin 1 (PMID:32968279). TRADD activity is further tuned by phosphorylation of death-domain SXXE/D motifs required for stable complex assembly (PMID:21724995) and by TAK1-dependent phosphorylation governing RIPK1-dependent cell death in intestinal epithelium (PMID:39987261), and it is targeted by bacterial effectors that arginine-GlcNAcylate it to block TNF signaling as an immune-evasion strategy (PMID:32766249).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Established TRADD as the proximal TNFR1 death-domain adaptor and showed that its apoptotic and NF-κB outputs are separable, defining the receptor as a bimodal signaling hub.

    Evidence Interaction screen, Co-IP, overexpression and crmA inhibitor dissection of TNFR1 death domain binding

    PMID:7758105

    Open questions at the time
    • Effector partners downstream of TRADD not yet identified
    • Endogenous receptor-complex dynamics not addressed by overexpression
  2. 1996 High

    Resolved how the two outputs bifurcate by showing TRADD directly recruits TRAF2 (NF-κB) and FADD (apoptosis) as separable branches, and mapped TRADD as an obligate intermediate.

    Evidence Reciprocal Co-IP, dominant-negative TRAF2/FADD epistasis, alanine-scanning mutagenesis of the death domain with NF-κB/apoptosis readouts

    PMID:8565075 PMID:8621670

    Open questions at the time
    • Structural basis of TRADD–TRAF2/FADD selectivity not yet defined
    • Determinants of branch choice in physiological cells unknown
  3. 1999 High

    Defined where TNFR1–TRADD assembly occurs, showing TRADD binds receptor only at the plasma membrane within 1 min of TNF and requires endocytosis-competent receptor.

    Evidence Confocal imaging, subcellular fractionation, Co-IP, hypertonic block of endocytosis

    PMID:9916731

    Open questions at the time
    • Trafficking signals controlling TRADD's resting Golgi localization unresolved
    • Role of internalized receptor complexes in signaling not defined
  4. 2000 High

    Provided the structural and biophysical basis for TRADD-mediated TRAF2 recruitment, showing a unique high-affinity binding mode that explains preferential signaling through TRADD over direct receptor–TRAF2 contact.

    Evidence Crystal structure of TRADD–TRAF2, NMR structure of N-TRADD, SPR affinity measurements, in vivo signaling assays

    PMID:10892748 PMID:10911999

    Open questions at the time
    • Structure of full-length TRADD with both domains not solved
    • FADD-binding interface not structurally characterized in these studies
  5. 2002 High

    Discovered that TRADD shuttles between cytoplasm and nucleus and that nuclear TRADD activates a PML/p53-dependent, caspase-independent apoptosis pathway distinct from the cytoplasmic FADD/caspase-8 route.

    Evidence NLS/NES mutant localization, dominant-negative FADD, caspase and Bcl-xL manipulation, PML-deficient cells

    PMID:12045187

    Open questions at the time
    • Physiological signals driving nuclear shuttling not defined
    • Nuclear binding partners not yet identified
  6. 2004 Medium

    Assigned a nuclear regulatory function by showing TRADD forms a nuclear STAT1-α complex and dampens IFN-γ/STAT1 signaling.

    Evidence Co-IP, subcellular fractionation, antisense knockdown with STAT1 phosphorylation/DNA-binding readouts

    PMID:14730360

    Open questions at the time
    • Single-lab knockdown without genetic confirmation here
    • Mechanism by which nuclear TRADD limits STAT1 phosphorylation unresolved
  7. 2006 High

    Clarified branch selection at the receptor by demonstrating TRADD and RIPK1 compete for TNFR1 recruitment, with TRADD required for NF-κB and caspase-8 apoptosis but dispensable for RIP1-dependent necrosis.

    Evidence siRNA knockdown in primary T cells, NF-κB and caspase-8 readouts, TNFR1 complex Co-IP

    PMID:16611992

    Open questions at the time
    • Molecular determinants of TRADD-vs-RIPK1 occupancy not defined
    • Necroptotic machinery downstream not characterized here
  8. 2008 High

    Genetic knockout established TRADD as the in vivo organizer of the TNFR1 signaling complex and a contributor to TRIF-dependent TLR signaling, with cell-type-dependent (RIP1-compensated) requirements.

    Evidence TRADD-KO mice, TNFR1/TLR4 complex Co-IP, RIP1 ubiquitination, NF-κB/MAPK assays, in vivo TNF/LPS/poly(I:C) challenge

    PMID:18641653 PMID:18641654 PMID:18719121

    Open questions at the time
    • Basis for macrophage vs MEF differential requirement only partially explained
    • Contribution of nuclear TRADD functions to these phenotypes not separated
  9. 2008 High

    Extended TRADD to antiviral immunity by showing it is recruited to MAVS/Cardif to assemble a TRAF3–TANK–FADD–RIP1 complex driving IRF3/NF-κB and type-I IFN responses.

    Evidence Co-IP with Cardif, siRNA knockdown, IFN-β reporter, VSV replication assay

    PMID:18439848

    Open questions at the time
    • Stoichiometry and assembly order of the MAVS complex not resolved
    • Whether nuclear TRADD contributes to antiviral output unknown
  10. 2011 Medium

    Generalized TRADD as a shared death-receptor adaptor (DR3/TL1A) and identified phosphorylation of death-domain SXXE/D motifs as a requirement for stable TNFR1–TRADD complex formation.

    Evidence TRADD-KO T cells with DR3 complex Co-IP and proliferation/NF-κB readouts; phospho-specific antibodies and SXXE/D mutagenesis

    PMID:21421854 PMID:21724995

    Open questions at the time
    • Kinase(s) phosphorylating TRADD S215/S296 not identified here
    • Dynamics of phosphorylation during signaling not measured
  11. 2012 High

    Defined a TNFR1-independent nuclear tumor-suppressive function by showing TRADD stabilizes p19Arf via modulation of ULF-mediated ubiquitination, promoting senescence and restraining carcinogenesis.

    Evidence TRADD-KO mice, chemical carcinogenesis and HRas senescence assays, TRADD–ULF–p19Arf Co-IP, protein stability assay

    PMID:22561347

    Open questions at the time
    • How nuclear TRADD biochemically interferes with ULF–p19Arf engagement not detailed
    • Relationship to its receptor signaling role unclear
  12. 2017 High

    Provided structural detail of the TRADD death domain and a second nuclear function in genome maintenance, showing TRADD facilitates NHEJ by recruiting 53BP1 and Ku70/Ku80 to DSBs.

    Evidence NMR structure of TRADD-DD with novel fold; γH2AX foci, NHEJ-factor Co-IP, KO/NLS mutants, JNK/ROS measurements

    PMID:28611389 PMID:28765645

    Open questions at the time
    • Signal targeting TRADD to break sites not defined
    • DNA-repair role validated in a single lab without independent confirmation
  13. 2018 High

    Resolved how RIPK1 controls TRADD output in vivo, showing RIPK1 normally restrains TRADD from forming FADD–caspase-8 complexes; its loss unleashes TRADD-driven, TNFR1-independent apoptosis.

    Evidence Ripk1-/-Tradd-/- double-KO mice, genetic epistasis, caspase-8 activation, histopathology

    PMID:30185824

    Open questions at the time
    • Molecular basis of RIPK1's restraint on TRADD not defined
    • Which receptor or platform nucleates TNFR1-independent complexes unknown
  14. 2019 Medium

    Refined TRADD's role at TRAIL receptors and its anti-necroptotic, RIPK1-redundant functions, showing context-dependent pro-survival and pro-inflammatory roles.

    Evidence TRADD-KO MEFs and CRISPR single/double KO panels in RIPK3-expressing cells, apoptosis/necroptosis/NF-κB readouts, rescue

    PMID:21187341 PMID:30741924

    Open questions at the time
    • Mechanism by which TRADD limits FADD recruitment at TRAIL receptors not structurally defined
    • Single-lab CRISPR panels for redundancy claims
  15. 2020 High

    Connected TRADD to autophagy and proteostasis and identified druggable control, showing it suppresses TRAF2/cIAP-mediated K63-ubiquitination of Beclin 1 and that small molecules binding TRADD-N modulate RIPK1 and Beclin 1 ubiquitination; also revealed RIPK1-independent necroptosis via RIPK3 and bacterial GlcNAcylation as an evasion mechanism.

    Evidence TRADD-KO cells, Beclin 1 ubiquitination/autophagy flux, small-molecule binding (ICCB-19/Apt-1), tau P301S proteinopathy mouse; TRADD–RIPK3 Co-IP; SseK1/NleB GlcNAcylation site mapping and mouse infection

    PMID:32039207 PMID:32766249 PMID:32968279

    Open questions at the time
    • In vivo relevance of the RIPK3-direct necroptosis branch limited to RIPK1-depleted lines
    • How GlcNAcylation at Arg235/245 structurally blocks signaling not fully resolved
  16. 2021 High

    Structurally defined TRADD–p75NTR engagement and confirmed receptor degradation control, showing TRADD-DD binds the p75NTR-DD homodimer interface to regulate neuronal NF-κB survival, while RIPK1 prevents TNF-induced TRADD ubiquitination/degradation.

    Evidence NMR structure of p75NTR-DD–TRADD-DD complex with mutagenesis and neuronal NF-κB assays; RIPK1-KO/TRADD-KO human cells with degradation and NIK/ripoptosome readouts

    PMID:34175311 PMID:34830347

    Open questions at the time
    • Physiological p75NTR ligand context for TRADD recruitment not addressed
    • Identity of the ligase degrading TRADD upon RIPK1 loss not defined
  17. 2025 High

    Identified TAK1-dependent phosphorylation as a regulator of TRADD/RIPK1 cooperative cell death in epithelium and linked TRADD-driven death programs to disease, including diabetic cardiomyopathy pyroptosis driven by XBP1-induced TRADD expression.

    Evidence TAK1 IEC-KO and TRADD-KO mice with RIPK1-inhibitor epistasis and intestinal pathology; XBP1 ChIP on TRADD promoter, STZ diabetic mice with TRADD KO/Apt-1, pyroptosis and echocardiography

    PMID:39753984 PMID:39987261

    Open questions at the time
    • TAK1 phosphosites on TRADD and their mechanistic effect not fully mapped
    • Direct molecular link between TRADD and pyroptotic machinery not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRADD partitions among its membrane-proximal adaptor function, nuclear DNA-repair/senescence/STAT1 roles, and autophagy/proteostasis control — and what signals govern this partitioning — remains unresolved.
  • No structure of full-length TRADD in a receptor complex
  • Signals controlling nuclear vs cytoplasmic distribution undefined
  • Quantitative rules governing TRAF2 vs FADD vs RIPK1 branch selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 1 R-HSA-9612973 Autophagy 1
Partners
FADDMAVSP75NTRRIPK1RIPK3STAT1TNFR1TRAF2
Complex memberships
DR3 (TL1A) signaling complexMAVS/Cardif antiviral complex (TRAF3-TANK-FADD-RIP1)TNFR1 signaling complexTRADD-FADD-caspase-8 complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TRADD (34 kDa) was identified as a protein that specifically interacts with the intracellular death domain of TNFR1; overexpression of TRADD induces both apoptosis and NF-κB activation, and the C-terminal 118 amino acids are sufficient for both activities and for TNFR1 death domain interaction. TRADD-mediated cell death is suppressible by crmA (an ICE inhibitor), but NF-κB activation by TRADD is not inhibited by crmA, demonstrating that the two signaling pathways are distinct downstream of TRADD. Protein interaction screen, co-immunoprecipitation, overexpression, dominant-negative mutants, crmA inhibitor assay Cell High 7758105
1996 TRADD directly interacts with both TRAF2 and FADD, defining two distinct TNFR1 signaling cascades: the TRADD–TRAF2 branch activates NF-κB, and the TRADD–FADD branch induces apoptosis. A dominant-negative TRAF2 (lacking N-terminal RING finger) blocks NF-κB but not apoptosis; a dominant-negative FADD (lacking N-terminal 79 aa) blocks apoptosis but not NF-κB, establishing that these pathways bifurcate at TRADD. Co-immunoprecipitation, dominant-negative mutant overexpression, NF-κB reporter assay, apoptosis assay Cell High 8565075
1996 Alanine scanning mutagenesis of the TRADD death domain showed that mutations affecting distinct activities (cell killing vs. NF-κB activation) are distributed throughout the domain rather than mapping to discrete regions. A specific mutant was identified that separates cell killing from NF-κB activation. Additionally, a dominant-negative TRADD death domain mutant blocked TNF-induced NF-κB activation, establishing TRADD as an obligate intermediate. Systematic alanine scanning mutagenesis, NF-κB reporter assay, apoptosis assay, dominant-negative overexpression The Journal of biological chemistry High 8621670
1999 By confocal microscopy and cell fractionation/co-immunoprecipitation, TRADD is concentrated in the cis/medial-Golgi in untreated cells, while TNF-R1 is principally in the trans-Golgi network. Upon TNF stimulation, TRADD binds TNF-R1 exclusively at the plasma membrane within 1 min, and this association is prevented when receptor-mediated endocytosis is blocked. No TRADD–TNF-R1 association was detected in the Golgi in response to exogenous TNF. Confocal immunofluorescence microscopy, subcellular fractionation, co-immunoprecipitation, hypertonic medium to block endocytosis Journal of immunology High 9916731
2000 Crystal structure of the TRADD–TRAF2 complex revealed a binding mode highly distinct from direct receptor–TRAF2 interactions. The TRADD–TRAF2 interaction has significantly stronger affinity than receptor–TRAF2. TRADD is specific for TRAF1 and TRAF2, ensuring cIAP recruitment to the signaling complex for direct inhibition of caspase activation. In vivo signaling assays showed TRAF2 signaling is more readily initiated by TRADD than by direct receptor–TRAF2 interactions. Crystal structure determination, BIAcore surface plasmon resonance affinity measurements, in vivo signaling assay Cell High 10892748
2000 NMR solution structure of the N-terminal domain of TRADD (N-TRADD) revealed a novel protein fold. Combined NMR, BIAcore, and mutagenesis experiments identified the interaction site of N-TRADD with the C-terminal domain of TRAF2 (C-TRAF2), establishing the structural basis for N-TRADD-mediated recruitment of TRAF2 to TNFR1 and downstream JNK/AP-1 and NF-κB activation. NMR structure determination, BIAcore SPR, mutagenesis Molecular cell High 10911999
2000 Stat1 forms a complex with TNFR1 and TRADD in a TNF-α-dependent manner. In vitro recombinant protein binding studies showed Stat1 directly interacts with TNFR1 and TRADD but not FADD, RIP, or TRAF2. In Stat1-deficient cells, TRADD–RIP and TRADD–TRAF2 complex formation is enhanced, leading to increased NF-κB activation; overexpression of Stat1 blocked NF-κB activation by TNF-α, establishing Stat1 as a negative regulator of the TNFR1–TRADD signaling complex. Antibody array screening, co-immunoprecipitation, in vitro recombinant protein-protein interaction, NF-κB reporter assay in Stat1-deficient cells Molecular and cellular biology Medium 10848577
2001 Keratin 18 (K18) was identified as a TRADD-binding protein; the C-terminal region of TRADD interacts with the coil Ia of the K18 rod domain. Endogenous TRADD co-immunoprecipitated with K18 and colocalized with K8/K18 filaments. Overexpression of K18 N-terminus (TRADD-binding domain) or K8/K18 rendered cells more resistant to TNF-induced killing, and this correlated with inhibition of caspase-8 activation. K18 is proposed to sequester TRADD away from activated TNFR1. Yeast two-hybrid, co-immunoprecipitation, confocal colocalization, overexpression, caspase-8 activity assay The Journal of cell biology High 11684708
2002 TRADD contains functional nuclear export and import sequences allowing it to shuttle between cytoplasm and nucleus. In the absence of nuclear export, TRADD accumulates in nuclear structures associated with PML nuclear bodies. Nuclear TRADD death domain activates a distinct apoptosis pathway that is PML-dependent, involves p53, is inhibited by Bcl-xL but not by caspase inhibitors or dominant-negative FADD. Conversely, cytoplasmic TRADD apoptosis is resistant to Bcl-xL but sensitive to caspase inhibitors and DN-FADD. Fluorescence localization of NLS/NES mutants, dominant-negative FADD, caspase inhibitors, Bcl-xL overexpression, PML-deficient cells The Journal of cell biology High 12045187
2002 A20 (an NF-κB-inducible zinc finger protein) protects IKKγ-deficient Jurkat cells from TNF-induced apoptosis by disrupting recruitment of TRADD and RIP to the TNFR1 signaling complex, establishing that A20 acts upstream of TRADD at the receptor complex level. IKKγ-deficient Jurkat mutant cells, co-immunoprecipitation of receptor signaling complex, apoptosis assays, A20 overexpression Molecular and cellular biology Medium 12167698
2002 FKHR (Forkhead) transcription factor-dependent TRADD promoter transactivation was demonstrated: chemotherapeutic drug-induced Akt inactivation leads to nuclear FKHR which binds a Forkhead-responsive element in the TRADD promoter to upregulate TRADD expression, contributing to apoptosis. Overexpression of dominant-negative TRADD mutants attenuated drug-induced apoptosis. cDNA microarray, TRADD promoter analysis, luciferase reporter assay, dominant-negative TRADD overexpression Molecular and cellular biology Medium 12446787
2004 IFN-γ induces formation of a nuclear-localized TRADD–STAT1-α complex. TRADD knockdown prolongs IFN-γ-mediated STAT1-α phosphorylation, increases STAT1-α DNA-binding activity, nuclear presence, and transcriptional potential, indicating TRADD negatively regulates IFN-γ/STAT1-α signaling from within the nucleus. Co-immunoprecipitation, subcellular fractionation, TRADD antisense knockdown, STAT1 phosphorylation and DNA-binding assays Nature immunology Medium 14730360
2005 Cytoplasmic TRADD activates apoptosis through FADD and caspase-8 (blocked by caspase inhibitors or DN-FADD), while nuclear TRADD (death domain only) activates a distinct pathway requiring caspase-9 catalytic activity but only partial Apaf-1 dependence, and this pathway is blocked only by combining caspase inhibitors with a serine protease inhibitor. NLS/NES mutants for forced nuclear/cytoplasmic localization, dominant-negative FADD, caspase inhibitors, Apaf-1-deficient cells, caspase-9 catalytic mutant Cell death and differentiation High 15761471
2006 siRNA-mediated TRADD silencing demonstrated that TRADD is required for TNFR1-induced NF-κB activation and caspase-8-dependent apoptosis, but is dispensable for TNFR1-initiated RIP1-dependent necrosis. TRADD and RIP1 compete for recruitment to the TNFR1 signaling complex, and their independent association determines whether NF-κB activation, apoptosis, or nonapoptotic necrotic death is triggered. siRNA knockdown in primary T cells, NF-κB reporter assay, caspase-8 activity, flow cytometry for necrosis/apoptosis, co-immunoprecipitation of TNFR1 complex Molecular and cellular biology High 16611992
2008 TRADD is recruited to the mitochondrial antiviral signaling adaptor Cardif/MAVS and orchestrates formation of a complex including TRAF3, TANK, FADD, and RIP1, leading to IRF3 and NF-κB activation. Loss of TRADD prevented Cardif-dependent IFN-β activation and reduced IFN-β production in response to RNA viruses (RIG-I/MDA5 pathway), enhancing VSV replication. Co-immunoprecipitation of TRADD with Cardif, siRNA knockdown, IFN-β reporter assay, viral replication assay (VSV) Immunity High 18439848
2008 TRADD-deficient mice (genetic knockout) showed abrogated TNF-induced apoptosis, prevented recruitment of TRAF2 and RIP1 ubiquitination in the TNFR1 signaling complex, and considerably inhibited NF-κB and MAPK activation. TRIF-dependent cytokine production in response to poly(I:C) and LPS was impaired in TRADD-deficient cells, with TRADD-dependent RIP1 ubiquitination and NF-κB activation in fibroblasts but not macrophages. TRADD knockout mice, co-immunoprecipitation of TNFR1 complex, ubiquitination assay, NF-κB/MAPK activation assays, cytokine ELISA Nature immunology High 18641654
2008 TRADD-deficient mice showed that TRADD orchestrates TNFR1 signaling complex formation and is essential for TNFR1 signaling in mouse embryonic fibroblasts but partially dispensable in macrophages (where abundant RIP expression compensates). TRADD is also required for TRIF-dependent TLR signaling in MEFs but not macrophages. TRADD-deficient mice were resistant to TNF, LPS, and poly(I:C) toxicity. TRADD knockout mice, MEF and macrophage cell culture assays, NF-κB reporter, cytokine production, in vivo TNF/LPS challenge Nature immunology High 18641653
2008 In TRADD-deficient mouse T cells, TNFα-mediated apoptosis and TNFα-stimulated NF-κB, JNK, and ERK activation are defective. TRADD is important for germinal center formation and DR3-mediated costimulation of T cells. TRADD participates in the TLR4 complex formed upon LPS stimulation, and TRADD-deficient macrophages show impaired cytokine production in response to TLR ligands. TRADD deficiency does not affect IFN-γ-induced signaling. TRADD knockout mice, T-cell functional assays, germinal center analysis, TLR4 complex co-immunoprecipitation, cytokine ELISA PNAS High 18719121
2011 TRADD is essential for DR3 (death receptor 3) signaling by TL1A: TRADD KO T cells lack TL1A-induced proliferation and show dramatically reduced MAPK signaling and NF-κB activation. TRADD is required for recruitment of RIP1 and TRAF2 to the DR3 signaling complex and for RIP1 ubiquitination. TRADD KO mouse T cells, proliferation assay, NF-κB/MAPK activation, co-immunoprecipitation of DR3 complex, ubiquitination assay Journal of immunology High 21421854
2011 Phosphorylation of SXXE/D motifs in the death domains of TNFR1 (S381) and TRADD (S215, S296) is required for stable TNFR1–TRADD complex formation and subsequent NF-κB activation. Phospho-S215LKD and phospho-S296LAE in TRADD are also critical for recruiting FADD and RIP1. IKKβ phosphorylates TNFR1 at S381, facilitating T-cell migration and accumulation. Phospho-specific antibodies, mutagenesis of SXXE/D motifs, co-immunoprecipitation, NF-κB reporter assay, T-cell migration assay Journal of immunology Medium 21724995
2012 TRADD shuttles into the nucleus to modulate interaction between p19Arf and its E3 ubiquitin ligase ULF, promoting p19Arf protein stability. Tradd-deficient primary cells show reduced p19Arf accumulation and decreased susceptibility to HRas-induced senescence, and Tradd-deficient mice show accelerated chemical carcinogenesis, establishing a tumor-suppressive role for nuclear TRADD independent of TNFR1 signaling. TRADD KO mice, chemical carcinogenesis model, HRas-induced senescence assay, co-immunoprecipitation of TRADD–ULF–p19Arf, p19Arf protein stability assay Nature cell biology High 22561347
2012 GST pull-down and Biacore biosensor experiments established direct binding interactions among the death domains of TNFR1, TRADD, and RIP1. Structure-based mutations of TNFR1 (P367A/P368A), TRADD (F266A), and RIP1 (M637A/R638A) disrupted death domain complex formation and prevented stable interactions. GST pull-down, Biacore biosensor, structure-guided mutagenesis Biochemical and biophysical research communications Medium 24361886
2013 EVER2 interacts with the N-terminal domain of TRADD, which impairs the recruitment of TRAF2 and RIPK1 to TRADD and promotes TNF-α- and TRAIL-dependent apoptosis. A skin cancer-associated EVER2 allele (I306) shows impaired TRADD–EVER2 interaction and reduced cell death following TNF-α treatment. Co-immunoprecipitation, EVER2 mutant analysis, apoptosis assay, TRAF2/RIPK1 recruitment assay Cell death & disease Medium 23429285
2017 NMR solution structure of the TRADD C-terminal death domain (TRADD-DD) revealed a novel fold within the death domain superfamily comprising an all-helix Greek key motif and a β-hairpin motif flanked by two α-helices. The β-hairpin is essential for folding. NMR titration revealed a direct weak interaction between TRADD-DD and p75NTR-DD monomers, with a binding site near the p75NTR-DD homodimerization interface, suggesting TRADD recruitment requires separation of the p75NTR DD homodimer. High-resolution NMR structure determination, NMR titration Scientific reports High 28765645
2017 Nuclear TRADD translocates to DNA double-strand break (DSB) sites during the DNA damage response and facilitates non-homologous end-joining (NHEJ) repair by recruiting 53BP1 and the Ku70/Ku80 complex. TRADD deficiency or cytoplasmic sequestration leads to accumulation of γH2AX foci after DNA damage. TRADD is dispensable for homologous recombination repair. Impaired nuclear TRADD localization triggers cell death via persistent JNK activation and ROS accumulation. Immunofluorescence of γH2AX foci, co-immunoprecipitation of NHEJ factors (53BP1, Ku70/Ku80), TRADD KO/knockdown, NLS mutant constructs, JNK and ROS measurements Scientific reports Medium 28611389
2018 In Ripk1-/- mice, genetic deletion of Tradd reduces systemic cell death, inflammation, intestinal and thymic pathology, and anemia by blocking TRADD-driven FADD–caspase-8 complex formation and caspase-8 activation. These data show that RIPK1 normally prevents TRADD from forming a FADD–caspase-8 complex, and that TRADD-dependent apoptosis in Ripk1-/- animals is TNFR1-independent. Ripk1-/-Tradd-/- double-KO mice, genetic epistasis, caspase-8 activation assays, histopathology Cell death and differentiation High 30185824
2019 In TRADD-deficient mouse embryonic fibroblasts, TRAIL-induced apoptosis is paradoxically enhanced (TRADD has a survival role in TRAIL signaling). TRADD is recruited to the TRAIL receptor complex and mediates RIP1 recruitment; TRADD limits FADD binding to the receptor complex, reducing caspase activation. TRADD also mediates RIP1-dependent non-apoptotic ERK signaling downstream of TRAIL receptors. TRADD KO MEFs, TRAIL treatment, FACS apoptosis assay, co-immunoprecipitation of TRAIL receptor complex, ERK assay, TRADD rescue FASEB journal High 21187341
2020 TRADD modulates cellular homeostasis by inhibiting K63-linked ubiquitination of Beclin 1 mediated by TRAF2, cIAP1, and cIAP2, thereby reducing autophagy. TRADD deficiency inhibits both RIPK1-dependent extrinsic apoptosis and proteasomal stress-induced intrinsic apoptosis. Small molecules ICCB-19 and Apt-1 bind to a pocket on the N-terminal TRAF2-binding domain of TRADD (TRADD-N), which interacts with TRADD-C and TRAF2 to modulate ubiquitination of RIPK1 and Beclin 1. TRADD KO cells, ubiquitination assay for Beclin 1, autophagy flux measurement, small molecule binding assay, in vivo mouse model of proteinopathy (mutant tau P301S), proteostasis assay Nature High 32968279
2020 TRADD mediates RIPK1-independent necroptosis induced by TNF in RIPK1-knockdown L929 and HT-22 cells. Mechanistically, TRADD binds RIPK3 to form a new protein complex, facilitating RIPK3 oligomerization and phosphorylation, thereby activating the RIPK3–MLKL signaling pathway. TRADD is also critical for ROS accumulation contributing to this necroptosis. RIPK1 knockdown, TRADD knockdown, co-immunoprecipitation of TRADD–RIPK3, RIPK3 phosphorylation assay, MLKL activation, ROS measurement, necroptosis assay Frontiers in cell and developmental biology Medium 32039207
2020 NleB (EPEC effector) and SseK1 (Salmonella effector) modify TRADD through arginine-GlcNAcylation. SseK1 modifies TRADD at Arg235/Arg245, disrupting TNF signaling. Mouse infection studies showed SseK1 rescues bacterial colonization deficiency via TRADD (in vivo substrate), demonstrating that bacteria exploit GlcNAcylation of TRADD as an immune evasion strategy. Substrate screen of 12 DD proteins, GlcNAcylation assays, site-directed mutagenesis (Arg235/Arg245), mouse infection model Frontiers in cell and developmental biology High 32766249
2021 RIPK1 is essential for preventing TNF-induced ubiquitination and degradation of TRADD. In RIPK1 KO human cell lines, TRADD undergoes TNF-induced ubiquitination and degradation. TRADD acts as a negative regulator of NIK stabilization and subsequent ripoptosome formation; TRADD is required for apoptosis but dispensable for necroptosis. RIPK1 and TRADD do not appear essential for MAPK signaling activation. RIPK1 KO and TRADD KO human cell lines (CRISPR), ubiquitination/degradation assay, apoptosis/necroptosis readouts, NIK stabilization assay International journal of molecular sciences Medium 34830347
2021 NMR structure of the p75NTR death domain–TRADD death domain complex revealed that TRADD-DD is specifically recognized by p75NTR-DD mainly through electrostatic interactions. The binding site is adjacent to the p75NTR-DD homodimerization interface, indicating that TRADD recruitment requires separation of the p75NTR-DD homodimer. In cerebellar granule neurons, TRADD–p75NTR interaction regulates canonical NF-κB signaling and cell survival. NMR structure of the complex, mutagenesis, co-immunoprecipitation, NF-κB reporter assay in cerebellar granule neurons The Journal of biological chemistry High 34175311
2015 Calmodulin (CaM) binds directly to TRADD death domain via a calcium-dependent site in α-helices 1–2. Both N- and C-terminal domains of CaM are important for TRADD binding. Oxidation of CaM methionines drastically reduces CaM affinity for TRADD. CaM pull-down assays, mutagenesis (CaM Met-to-Leu mutants), TRADD death domain α-helix mutagenesis, oxidized CaM binding assay PLoS one Medium 25643035
2016 IRF-1 binds the TRADD gene promoter to promote its transcription in response to sublytic C5b-9 and p38 MAPK activation in glomerular mesangial cells. TRADD then activates caspase-8 leading to apoptosis. Silencing MEKK2, p38 MAPK, IRF-1, or TRADD in vivo inhibited mesangial cell apoptosis in Thy-1 nephritis rats. IRF-1 chromatin immunoprecipitation (ChIP) on TRADD promoter, siRNA knockdown of MEKK2/IRF-1/TRADD in vivo, caspase-8 activation assay Journal of immunology Medium 28039298
2025 TAK1 phosphorylates TRADD, and this phosphorylation modulates RIPK1-dependent apoptosis. TRADD and RIPK1 act cooperatively to mediate cell death regulated by TNF and TLR signaling in intestinal epithelial cells; RIPK1-dependent ileitis evolves to RIPK1- and TRADD-co-dependent colitis in TAK1 IEC-deficient conditions. Combined RIPK1 inhibition and TRADD knockout completely protects against intestinal pathology and lethality in TAK1 IEC KO mice. TAK1 IEC KO mice, TRADD KO mice, double RIPK1 inhibitor + TRADD KO genetic/pharmacological epistasis, intestinal pathology, cell death assays, microbiota analysis Nature communications High 39987261
2025 High glucose treatment increases XBP1 expression, which binds the TRADD promoter to elevate TRADD expression in cardiomyocytes. TRADD-mediated pyroptosis contributes to diabetic cardiomyopathy (DCM): TRADD knockdown or treatment with the TRADD inhibitor Apt-1 significantly reduces pyroptosis, myocardial hypertrophy, and fibrosis in diabetic mice. XBP1 ChIP on TRADD promoter, TRADD knockdown/KO in STZ diabetic mouse model, Apt-1 pharmacological inhibition, pyroptosis assay, cardiac echocardiography Acta pharmacologica Sinica Medium 39753984
2019 TRADD redundantly mediates NF-κB and proinflammatory signaling with RIPK1 in response to both TNF and TRAIL. TRADD has an anti-necroptotic function: in RIPK3-expressing HeLa cells lacking TRADD, TNF- and TRAIL-induced necroptosis is enhanced. TRADD and RIPK1 act redundantly in TNF-induced but not TRAIL-induced apoptosis, while FADD alone is sufficient for TRAIL- but not TNF-induced apoptosis. CRISPR KO of TRADD, RIPK1, FADD (single and double KO) in RIPK3-expressing HeLa cells; apoptosis, necroptosis, NF-κB assays Cell death & disease Medium 30741924
2014 The APL fusion protein NPM-RAR directly binds TRADD, impairing TNF-induced signaling through TRADD and blunting TNF-mediated activation of caspase-8 and caspase-3, while being permissive for NF-κB and JNK activation. This establishes a selective block of extrinsic apoptosis via TRADD sequestration. Proteomic identification of NPM-RAR binding partners, co-immunoprecipitation, colocalization, caspase-3/caspase-8 activation assay, NF-κB reporter Molecular cancer research Medium 25033841

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 1735 7758105
1996 TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 1709 8565075
2008 TRADD protein is an essential component of the RIG-like helicase antiviral pathway. Immunity 253 18439848
2008 Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nature immunology 222 18641654
2006 Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-kappaB activation and proliferation in human head and neck squamous cell carcinoma. Oncogene 183 16953224
2008 The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors. Nature immunology 175 18641653
1999 Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2. Journal of virology 172 9882303
2000 A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 160 10892748
2002 A20 inhibits tumor necrosis factor (TNF) alpha-induced apoptosis by disrupting recruitment of TRADD and RIP to the TNF receptor 1 complex in Jurkat T cells. Molecular and cellular biology 159 12167698
2001 Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD. The Journal of cell biology 147 11684708
2000 Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation. Molecular and cellular biology 141 10848577
1998 TNF receptor death domain-associated proteins TRADD and FADD signal activation of acid sphingomyelinase. The Journal of biological chemistry 137 9488730
2006 Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Molecular and cellular biology 124 16611992
2012 The role of TRADD in death receptor signaling. Cell cycle (Georgetown, Tex.) 122 22333735
1999 TNF recruits TRADD to the plasma membrane but not the trans-Golgi network, the principal subcellular location of TNF-R1. Journal of immunology (Baltimore, Md. : 1950) 121 9916731
1999 The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein (RIP) but does not induce apoptosis or require RIP for NF-kappaB activation. Molecular and cellular biology 116 10409763
1999 LMP1 signal transduction differs substantially from TNF receptor 1 signaling in the molecular functions of TRADD and TRAF2. The EMBO journal 94 10228165
2020 Modulating TRADD to restore cellular homeostasis and inhibit apoptosis. Nature 93 32968279
2008 Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors. Proceedings of the National Academy of Sciences of the United States of America 92 18719121
2015 MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer. Molecular oncology 82 25732226
2005 PAK4 functions in tumor necrosis factor (TNF) alpha-induced survival pathways by facilitating TRADD binding to the TNF receptor. The Journal of biological chemistry 81 16227624
2001 Hepatitis C virus core protein enhances FADD-mediated apoptosis and suppresses TRADD signaling of tumor necrosis factor receptor. Virology 70 11336543
2002 Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms. The Journal of cell biology 66 12045187
1996 Systematic mutational analysis of the death domain of the tumor necrosis factor receptor 1-associated protein TRADD. The Journal of biological chemistry 66 8621670
2019 Redundant and receptor-specific activities of TRADD, RIPK1 and FADD in death receptor signaling. Cell death & disease 63 30741924
2007 Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis. Journal of neurochemistry 61 17666051
2018 RIPK1 prevents TRADD-driven, but TNFR1 independent, apoptosis during development. Cell death and differentiation 59 30185824
2020 SNHG9, delivered by adipocyte-derived exosomes, alleviates inflammation and apoptosis of endothelial cells through suppressing TRADD expression. European journal of pharmacology 53 32007500
2020 TRADD Mediates RIPK1-Independent Necroptosis Induced by Tumor Necrosis Factor. Frontiers in cell and developmental biology 52 32039207
2016 The ORF3 Protein of Genotype 1 Hepatitis E Virus Suppresses TLR3-induced NF-κB Signaling via TRADD and RIP1. Scientific reports 51 27270888
2011 The adaptor protein TRADD is essential for TNF-like ligand 1A/death receptor 3 signaling. Journal of immunology (Baltimore, Md. : 1950) 50 21421854
2005 The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm. Cell death and differentiation 50 15761471
2000 Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway. Molecular cell 49 10911999
2002 Involvement of FKHR-dependent TRADD expression in chemotherapeutic drug-induced apoptosis. Molecular and cellular biology 48 12446787
2010 The role of TRADD in TRAIL-induced apoptosis and signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 47 21187341
2007 A class of small molecules that inhibit TNFalpha-induced survival and death pathways via prevention of interactions between TNFalphaRI, TRADD, and RIP1. Chemistry & biology 46 17961823
2008 The viral oncoprotein LMP1 exploits TRADD for signaling by masking its apoptotic activity. PLoS biology 44 18198944
1999 The A20 protein interacts with the Epstein-Barr virus latent membrane protein 1 (LMP1) and alters the LMP1/TRAF1/TRADD complex. Virology 44 10544141
2015 Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma. Oncotarget 43 26164206
2004 TRADD interacts with STAT1-alpha and influences interferon-gamma signaling. Nature immunology 42 14730360
2018 Interleukin-35 Inhibits TNF-α-Induced Osteoclastogenesis and Promotes Apoptosis via Shifting the Activation From TNF Receptor-Associated Death Domain (TRADD)-TRAF2 to TRADD-Fas-Associated Death Domain by JAK1/STAT1. Frontiers in immunology 40 30061878
2007 Zfra affects TNF-mediated cell death by interacting with death domain protein TRADD and negatively regulates the activation of NF-kappaB, JNK1, p53 and WOX1 during stress response. BMC molecular biology 39 17567906
2004 Mutation analysis of the apoptotic "death-receptors" and the adaptors TRADD and FADD/MORT-1 in osteosarcoma tumor samples and osteosarcoma cell lines. International journal of cancer 39 14999771
2012 Ribosomal protein S3 interacts with TRADD to induce apoptosis through caspase dependent JNK activation. Biochemical and biophysical research communications 37 22510408
2016 Hydrogen sulfide protects against TNF-α induced neuronal cell apoptosis through miR-485-5p/TRADD signaling. Biochemical and biophysical research communications 36 27562714
2000 FADD and TRADD expression and apoptosis in primary hepatocellular carcinoma. World journal of gastroenterology 36 11819561
2008 Pursuing different 'TRADDes': TRADD signaling induced by TNF-receptor 1 and the Epstein-Barr virus oncoprotein LMP1. Biological chemistry 33 18713013
2021 Knockdown of circROBO2 attenuates acute myocardial infarction through regulating the miR-1184/TRADD axis. Molecular medicine (Cambridge, Mass.) 32 33658002
2013 EVER2 protein binds TRADD to promote TNF-α-induced apoptosis. Cell death & disease 32 23429285
2012 TRADD contributes to tumour suppression by regulating ULF-dependent p19Arf ubiquitylation. Nature cell biology 32 22561347
2011 TRADD is critical for resistance to TRAIL-induced cell death through NF-κB activation. FEBS letters 32 21627969
2020 Functional roles in cell signaling of adaptor protein TRADD from a structural perspective. Computational and structural biotechnology journal 31 33163147
2016 CFTR Controls the Activity of NF-κB by Enhancing the Degradation of TRADD. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 31 27960153
2021 RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation. International journal of molecular sciences 30 34830347
2001 Transcriptional activation of TRADD mediates p53-independent radiation-induced apoptosis of glioma cells. Oncogene 30 11420694
2021 Bacterial death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans. eLife 29 34061031
2023 Inhibition of TRADD ameliorates chondrocyte necroptosis and osteoarthritis by blocking RIPK1-TAK1 pathway and restoring autophagy. Cell death discovery 28 37002200
2013 Death domain complex of the TNFR-1, TRADD, and RIP1 proteins for death-inducing signaling. Biochemical and biophysical research communications 28 24361886
2022 Roles of the adaptor protein tumor necrosis factor receptor type 1-associated death domain protein (TRADD) in human diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 36076575
2009 The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD). Annals of the rheumatic diseases 24 19854717
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
2012 The viral TRAF protein (ORF111L) from infectious spleen and kidney necrosis virus interacts with TRADD and induces caspase 8-mediated apoptosis. PloS one 22 22615868
2019 MiR-199a-5p regulates rat liver regeneration and hepatocyte proliferation by targeting TNF-α TNFR1/TRADD/CASPASE8/CASPASE3 signalling pathway. Artificial cells, nanomedicine, and biotechnology 21 31682476
2001 Hepatitis C virus core protein potentiates c-Jun N-terminal kinase activation through a signaling complex involving TRADD and TRAF2. Virus research 21 11226577
2020 Arg-GlcNAcylation on TRADD by NleB and SseK1 Is Crucial for Bacterial Pathogenesis. Frontiers in cell and developmental biology 20 32766249
2019 Grouper TRADD Mediates Innate Antiviral Immune Responses and Apoptosis Induced by Singapore Grouper Iridovirus (SGIV) Infection. Frontiers in cellular and infection microbiology 20 31620373
2017 TRADD, TRAF2, RIP1 and TAK1 are required for TNF-α-induced pro-labour mediators in human primary myometrial cells. American journal of reproductive immunology (New York, N.Y. : 1989) 20 28337828
2013 Anticancer activity of an antisense oligonucleotide targeting TRADD combined with proteasome inhibitors in chemoresistant hepatocellular carcinoma cells. Journal of chemotherapy (Florence, Italy) 19 24070137
2017 Dynamic expression of death receptor adapter proteins tradd and fadd in Eimeria tenella-induced host cell apoptosis. Poultry science 18 28204749
2013 Effect of infliximab combined with methylprednisolone on expressions of NF-κB, TRADD, and FADD in rat acute spinal cord injury. Spine 18 23574812
2013 Agonist antibody activates death receptor 6 downstream signaling involving TRADD recruitment. FEBS letters 18 24374337
2022 Eriodictyol mediated selective targeting of the TNFR1/FADD/TRADD axis in cancer cells induce apoptosis and inhibit tumor progression and metastasis. Translational oncology 17 35462210
2015 TNFα triggers release of extracellular vesicles containing TNFR1 and TRADD, which can modulate TNFα responses of the parental cells. Archives of biochemistry and biophysics 17 26475675
2025 Cooperation of TRADD- and RIPK1-dependent cell death pathways in maintaining intestinal homeostasis. Nature communications 16 39987261
2017 Structure of the C-terminal domain of TRADD reveals a novel fold in the death domain superfamily. Scientific reports 16 28765645
2001 TRADD domain of Epstein-Barr virus transforming protein LMP1 is essential for inducing immortalization and suppressing senescence of primary rodent fibroblasts. Journal of virology 16 11222727
2000 The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells. Biochemical and biophysical research communications 16 11032752
2024 tRNA-derived fragment 3'tRF-AlaAGC modulates cell chemoresistance and M2 macrophage polarization via binding to TRADD in breast cancer. Journal of translational medicine 15 39080676
2016 Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis through the Cascade Pathway of MEKK2-p38 MAPK-IRF-1-TRADD-Caspase 8 in Rat Thy-1 Nephritis. Journal of immunology (Baltimore, Md. : 1950) 15 28039298
2013 Y14 positively regulates TNF-α-induced NF-κB transcriptional activity via interacting RIP1 and TRADD beyond an exon junction complex protein. Journal of immunology (Baltimore, Md. : 1950) 15 23817415
2006 EMAP-II facilitates TNF-R1 apoptotic signalling in endothelial cells and induces TRADD mobilization. Apoptosis : an international journal on programmed cell death 15 17051333
2021 Sertaconazole provokes proapoptotic autophagy via stabilizing TRADD in nonsmall cell lung cancer cells. MedComm 13 34977879
2017 TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3. Scientific reports 13 29170425
2021 Black carp TRADD suppresses MAVS/IFN signaling during the innate immune activation. Fish & shellfish immunology 12 33513437
2021 Structural basis of NF-κB signaling by the p75 neurotrophin receptor interaction with adaptor protein TRADD through their respective death domains. The Journal of biological chemistry 12 34175311
2021 miR-1184 regulates inflammatory responses and cell apoptosis by targeting TRADD in an LPS-induced cell model of sepsis. Experimental and therapeutic medicine 11 33936286
2014 Extrinsic apoptosis is impeded by direct binding of the APL fusion protein NPM-RAR to TRADD. Molecular cancer research : MCR 11 25033841
2011 Phospho-SXXE/D motif mediated TNF receptor 1-TRADD death domain complex formation for T cell activation and migration. Journal of immunology (Baltimore, Md. : 1950) 11 21724995
2025 TRADD-mediated pyroptosis contributes to diabetic cardiomyopathy. Acta pharmacologica Sinica 9 39753984
2021 Tumor necrosis factor receptor type 1-associated death domain (TRADD) regulates epithelial-mesenchymal transition (EMT), M1/M2 macrophage polarization and ectopic endometrial cysts formation in endometriosis. Annals of translational medicine 9 33569450
2025 Mogroside V ameliorates astrocyte inflammation induced by cerebral ischemia through suppressing TLR4/TRADD pathway. International immunopharmacology 8 39847949
2025 Downregulation of METTL3 enhances TRADD-mediated apoptosis in inflammatory bowel disease. Science China. Life sciences 8 40347213
2017 Nuclear TRADD prevents DNA damage-mediated death by facilitating non-homologous end-joining repair. Scientific reports 8 28611389
2015 N-terminal and C-terminal domains of calmodulin mediate FADD and TRADD interaction. PloS one 8 25643035
2017 Identification of TRADD as a potential biomarker in human uterine leiomyoma through iTRAQ based proteomic profiling. Molecular and cellular probes 7 28698006
2016 Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice. Biochemical and biophysical research communications 7 28013046
2015 NPM-RAR binding to TRADD selectively inhibits caspase activation, while allowing activation of NFκB and JNK. Leukemia & lymphoma 7 25791120
2023 Peptidomimetics for CVD screened via TRADD-TRAF2 complex interface assessments. In silico pharmacology 6 37899969
2020 Coronin 1B regulates the TNFα-induced apoptosis of HUVECs by mediating the interaction between TRADD and FADD. Biochemical and biophysical research communications 6 32303335
2020 miR-149-5p mitigates tumor necrosis factor-α-induced chondrocyte apoptosis by inhibiting TRADD. Archives of medical science : AMS 5 38757032

Missed literature

Know a paper Affinage missed for TRADD? Flag it for the maintainers and the community.

No submissions yet.