Affinage

TRAF1

TNF receptor-associated factor 1 · UniProt Q13077

Length
416 aa
Mass
46.2 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 37 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

TRAF1 is a RING finger-lacking adaptor of the TRAF family that couples TNF receptor superfamily members to NF-κB, JNK, ERK, and apoptotic signaling, acting as both a positive and negative modulator depending on receptor and dose (PMID:11672546, PMID:10544244). It binds TNFR superfamily members and viral mimics through a PXQXT/S-type core motif, engaging LMP1, CD30, and other receptors, where it coactivates NF-κB largely as part of TRAF1/TRAF2 heteroaggregates (PMID:8943365, PMID:9032281, PMID:9168896, PMID:8943059). Structurally, TRAF1 preferentially assembles into a TRAF1:(TRAF2)₂ heterotrimer whose TRAF-N coiled-coil drives trimerization and stability and whose TRAF-C surface forms the binding hotspot for partners such as cIAP2 and TANK; TRAF1 alone binds cIAP2 weakly, so its activity is largely exerted through TRAF2 (PMID:20385093, PMID:27151821, PMID:28155233). As a transcriptional target induced by NF-κB downstream of TNFR1, CD40, and IL-1R, TRAF1 participates with TRAF2 and cIAP1/2 in suppressing caspase-8 activation and blocking early TNF-induced apoptosis, and it stabilizes TRAF2 by displacing it from lipid rafts to sustain signaling over time (PMID:9733516, PMID:12370254, PMID:11395135). TRAF1 sets the threshold of multiple pathways: it restricts TNFR2-driven hyperproliferation and TNF-induced necrosis, dampens TLR-driven NF-κB by sequestering LUBAC components away from NEMO-directed linear ubiquitination, and limits constitutive NIK activity within the cIAP1/2:TRAF2:TRAF3:NIK complex (PMID:11672546, PMID:22570473, PMID:27893701). In CD8 T cells it is required for 4-1BB–driven ERK activation, Bcl-xL induction, and survival, defining a costimulatory survival function (PMID:18523273). Apoptotic caspase-8 cleavage at Asp-163 converts TRAF1 into a C-terminal dominant-negative fragment that associates with the IKK complex and sequesters released TRAF2, suppressing NF-κB and amplifying death signaling (PMID:11098060, PMID:12709429, PMID:11181075). TRAF1 also directly binds ASK1 to drive JNK-mediated, Akt-suppressing cell death in ischemic stroke and metabolic/inflammatory liver disease (PMID:24284943, PMID:26860405).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Established that TRAF1 is recruited to receptor cytoplasmic tails through a defined short linear motif and signals as part of TRAF1/TRAF2 heteroaggregates, defining its mode of receptor engagement.

    Evidence Co-IP, mutagenesis mapping of the PXQXT/S motif in LMP1 and CD30, and NF-κB reporter assays in EBV-transformed B cells

    PMID:8943059 PMID:8943365 PMID:9032281 PMID:9168896

    Open questions at the time
    • Did not resolve stoichiometry or structural basis of TRAF1:TRAF2 heteromers
    • Receptor selectivity rules between TRAF1, TRAF2, and TRAF3 not fully defined
  2. 1996 High

    Identified A20 as a feedback inhibitor recruited to the TRAF1/TRAF2 complex, embedding TRAF1 in a negative-regulatory circuit of NF-κB.

    Evidence Co-IP, deletion analysis, and NF-κB reporter assays

    PMID:8692885

    Open questions at the time
    • Direct contribution of TRAF1 (versus TRAF2) to A20 docking unresolved
  3. 1998 High

    Placed TRAF1 in a cooperative anti-apoptotic module that blocks caspase-8 activation at the earliest TNF checkpoint, linking it functionally to cell survival.

    Evidence NF-κB reporter assays, cotransfection with TRAF2/cIAP1/cIAP2, and caspase-8 activation assays

    PMID:9733516

    Open questions at the time
    • Relative contribution of TRAF1 within the four-protein module not dissected
    • Mechanism of caspase-8 suppression not defined at molecular level
  4. 2000 High

    Showed that caspase cleavage at Asp-163 converts TRAF1 into a dominant-negative fragment, revealing a switch that amplifies apoptosis by suppressing NF-κB.

    Evidence In vitro caspase-8 cleavage mapping, cleavage-site mutagenesis, in vivo apoptosis, and NF-κB reporter assays

    PMID:10692572 PMID:11098060

    Open questions at the time
    • Endogenous abundance and kinetics of the fragment in physiological apoptosis unclear
  5. 2001 High

    Defined TRAF1 as a negative regulator restricting TNFR2-specific TNF signaling in vivo, distinguishing receptor-selective roles.

    Evidence TRAF1-KO mice, T cell proliferation and NF-κB/AP-1 assays, TNFR1/TNFR2 receptor discrimination, and in vivo skin necrosis model

    PMID:11672546

    Open questions at the time
    • Molecular basis of TNFR2 versus TNFR1 selectivity not resolved
  6. 2002 High

    Explained one positive function: TRAF1 sustains signaling by displacing TRAF2 from lipid rafts and preventing its stimulus-dependent degradation.

    Evidence Lipid raft fractionation, co-IP, TRAF1-KO dendritic cells, and RING-domain swap constructs

    PMID:12370254

    Open questions at the time
    • Degradation machinery acting on TRAF2 not identified
    • How TRAF1 mechanistically blocks TRAF2 turnover unresolved
  7. 2003 Medium

    Mapped the cleavage fragment's inhibitory mechanism to direct constitutive association with the IKK complex via the N-TRAF domain.

    Evidence Co-IP with IKK, IKK kinase assays, NF-κB reporters, and TRAF-domain fragment overexpression

    PMID:12709429

    Open questions at the time
    • Single lab; physiological relevance of constitutive IKK association not validated in primary cells
    • Precise IKK subunit contact not defined
  8. 2008 High

    Defined a costimulatory survival function: TRAF1 is required for 4-1BB→ERK→Bcl-xL signaling that sustains CD8 T cell survival.

    Evidence TRAF1-KO mice, viral infection, ERK activation and Bcl-xL/Bim Westerns, and pharmacological ERK inhibition phenocopy

    PMID:18523273

    Open questions at the time
    • Direct link between TRAF1 and ERK activation machinery not biochemically mapped
  9. 2010 High

    Provided the structural basis for TRAF1's TRAF2-dependent activity, showing TRAF1:(TRAF2)₂ heterotrimers bind cIAP2 strongly while TRAF1 alone binds weakly.

    Evidence X-ray crystallography of TRAF2:cIAP2 and TRAF1:TRAF2:cIAP2, solution binding, and interface mutagenesis

    PMID:20385093

    Open questions at the time
    • Structures of TRAF1 bound to receptor tails not solved
    • Dynamics of heterotrimer assembly in cells not addressed
  10. 2012 High

    Showed TRAF1 tunes both canonical and alternative NF-κB by enabling 4-1BB-driven classical activation while restricting constitutive NIK within the cIAP:TRAF2:TRAF3:NIK complex.

    Evidence TRAF1-KO primary T cells, NIK siRNA epistasis, and NIK/TRAF3/cIAP Westerns with reporter assays

    PMID:22570473

    Open questions at the time
    • Stoichiometric control of NIK degradation by TRAF1 not quantified
  11. 2013 High

    Identified a direct TRAF1–ASK1 interaction driving JNK-mediated death and Akt suppression, extending TRAF1 function to ischemic neuronal injury.

    Evidence Genetic KO/overexpression in mouse stroke model, TRAF1-ASK1 co-IP, and JNK/Akt Westerns

    PMID:24284943

    Open questions at the time
    • ASK1-binding region of TRAF1 not mapped
    • Whether TRAF2 is required for the ASK1 interaction unresolved
  12. 2016 High

    Established that the TRAF1 MATH/TRAF-C domain binds LUBAC components to interfere with NEMO linear ubiquitination, defining a TNFR-independent brake on TLR-driven NF-κB.

    Evidence Direct binding assays to SHARPIN/HOIP/HOIL-1, co-IP, NEMO ubiquitination assays, and Traf1-KO LPS septic shock model

    PMID:27893701

    Open questions at the time
    • Quantitative competition between TRAF1 and NEMO for LUBAC not measured
  13. 2016 High

    Extended the TRAF1→ASK1 axis to metabolic disease, showing TRAF1 promotes hepatic steatosis and insulin resistance via ASK1-dependent P38/JNK activation.

    Evidence Global KO and liver-specific overexpression mice, obesity models, and in vivo ASK1 inhibitor epistasis

    PMID:26860405

    Open questions at the time
    • Cell-type-specific contributions to hepatic phenotype not fully separated
  14. 2018 Medium

    Linked TRAF1 to oncogenic kinase signaling by promoting ERK5 K184 ubiquitination and TRAF2-mediated BRAF ubiquitination in carcinogenesis models.

    Evidence TRAF1-KO carcinogenesis models, ERK5/BRAF ubiquitination assays, and ubiquitin-acceptor mutagenesis

    PMID:28131816 PMID:29748372

    Open questions at the time
    • TRAF1 lacks intrinsic ubiquitin ligase activity; the responsible E3 (likely TRAF2/cIAP) not definitively assigned
    • Single-lab findings per tumor context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRAF1 dose, phosphorylation, and partner composition switch it between positive and negative signaling at a given receptor remains unresolved.
  • No unified quantitative model integrating TRAF1:TRAF2 stoichiometry, PKN1 phosphorylation, and receptor context
  • Structures of full-length receptor-bound TRAF1 complexes lacking
  • In vivo relevance of caspase-cleavage fragment versus full-length TRAF1 not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3
Partners
ASK1CIAP2HOIPIKK2NIP45TANKTRAF2TRIF
Complex memberships
IKK complexLUBAC (SHARPIN/HOIP/HOIL-1) associated complexTRAF1:(TRAF2)2 heterotrimercIAP1/2:TRAF2:TRAF3:NIK complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NF-κB transcriptionally induces TRAF1, TRAF2, c-IAP1, and c-IAP2; these proteins act cooperatively to suppress caspase-8 activation and block TNF-α-mediated apoptosis at the earliest checkpoint. NF-κB reporter assays, cotransfection/overexpression, caspase-8 activation assays Science High 9733516
1996 TRAF1, TRAF2, and TRAF3 bind a single PXQXT/S core motif in the LMP1 cytoplasmic C-terminus (aa 199–214); in EBV-transformed B cells most TRAF1 and TRAF3 is associated with LMP1. TRAF1 coactivates NF-κB with LMP1 via TRAF1/TRAF2 heteroaggregates; dominant-negative TRAF2 blocks this, and TRAF3 is a negative modulator. Co-immunoprecipitation, alanine/deletion mutagenesis, NF-κB reporter cotransfection, EBV-transformed B cell fractionation Molecular and cellular biology High 8943365
1996 A20 interacts with the conserved C-terminal TRAF domain of TRAF1 and TRAF2 via its N-terminal half; A20's C-terminal zinc finger domain inhibits TRAF2-mediated NF-κB activation, identifying a two-domain feedback inhibitor recruited to the TRAF1/TRAF2 complex. Co-immunoprecipitation, deletion/mutational analysis, NF-κB reporter cotransfection assays Proceedings of the National Academy of Sciences of the United States of America High 8692885
1997 CD30 cytoplasmic domain contains two TRAF-binding motifs: membrane-proximal motif 576MLSVEEEG583 binds TRAF1 and TRAF2, while 558PHYPEQET565 binds TRAF2 and TRAF3. Coexpression of TRAF1 or TRAF2 (but not TRAF3) augments CD30 domain 2-mediated NF-κB activation; dominant-negative TRAF1 or TRAF2 inhibits this. Yeast two-hybrid, co-immunoprecipitation, NF-κB reporter cotransfection, deletion/dominant-negative analysis Molecular and cellular biology High 8943059 9032281 9168896
2010 Crystal structures of TRAF2:cIAP2 and TRAF1:TRAF2:cIAP2 complexes show that a TRAF2 trimer contacts cIAP2 via two chains; TRAF1 and TRAF2 preferentially form a TRAF1:(TRAF2)₂ heterotrimer that binds cIAP2 more strongly than TRAF2 alone. TRAF1 alone binds cIAP2 very weakly. Key interface residues confirmed by mutagenesis. X-ray crystallography, solution binding assays, site-directed mutagenesis Molecular cell High 20385093
2001 TRAF1-deficient mice show enhanced TNF signaling: TRAF1⁻/⁻ T cells respond to TNF via TNFR2 (p75) but not TNFR1 (p55) with hyperproliferation and elevated NF-κB/AP-1 activity, and skin is hypersensitive to TNF-induced necrosis, demonstrating TRAF1 is a negative regulator of TNFR2-mediated TNF signaling. Knockout mouse generation, T cell proliferation assays, NF-κB/AP-1 signaling assays, in vivo skin necrosis model Immunity High 11672546
2002 TRAF1 displaces TRAF2 from lipid rafts/detergent-insoluble fractions and prevents stimulus-dependent TRAF2 degradation, thereby sustaining TRAF2-dependent signaling over time. TRAF1⁻/⁻ dendritic cells show attenuated responses to secondary TRAF2-dependent stimulation and increased TRAF2 degradation. Lipid raft fractionation, co-immunoprecipitation, TRAF1-KO dendritic cell signaling assays, RING-finger domain swap constructs The Journal of experimental medicine High 12370254
2000 TRAF1 (but not TRAF2–6) is cleaved by caspase-8 at site ¹⁶⁰LEVD¹⁶³ during TNF-α- and Fas-induced apoptosis, generating a C-terminal fragment that suppresses NF-κB activation and enhances TNF receptor-1-mediated apoptosis. In vitro caspase cleavage assays, in vivo apoptosis induction, site-directed mutagenesis of cleavage site, NF-κB reporter assays, overexpression in HEK293T and HT1080 cells The Journal of biological chemistry High 11098060
2000 TRAF1 is cleaved after Asp-163 during Fas ligand-induced apoptosis; the C-terminal cleavage product acts as a dominant-negative form of TRAF1 that blocks TNF-induced NF-κB activation, providing a pro-apoptotic amplification mechanism. Apoptosis induction, Western blot cleavage analysis, NF-κB reporter assays FEBS letters Medium 10692572
2003 Caspase-derived C-terminal TRAF1 fragment (TRAF1-164–416) acts as a general inhibitor of NF-κB activation by directly associating with the IKK complex via the N-TRAF domain, whereas full-length TRAF1 modulates NF-κB differentially across TNF receptors. Full-length TRAF1 and the cleavage fragment are both constitutively associated with IKK. Co-immunoprecipitation with IKK complex, NF-κB reporter assays, IKK kinase assays, overexpression of TRAF domain fragments The Journal of biological chemistry Medium 12709429
2001 Caspase-8-generated C-terminal TRAF1 fragment co-immunoprecipitates with TRAF2 released from the TNFR1 complex during prolonged TNF treatment, sequestering TRAF2 and thereby reducing its anti-apoptotic signaling. Co-immunoprecipitation from TNF-stimulated cells, overexpression of TRAF1-c fragment, cell death assays Biochemical and biophysical research communications Medium 11181075
1999 TRAF1 promoter contains functional NF-κB binding sites; TNF-R1, CD40, and IL-1R trigger NF-κB-dependent TRAF1 transcription. Overexpressed TRAF1 prolongs TNF-induced JNK activation while a deletion mutant lacking the N-terminal region inhibits TNF-induced NF-κB and JNK activation. EMSA, promoter-reporter gene assays, RNase protection, transfection of deletion mutants The Journal of biological chemistry Medium 10383449
1999 Overexpression of TRAF1 in HEK293T cells completely prevented NF-κB activation induced by TNF, IL-1, overexpression of TRAF2, or TRAF6, identifying TRAF1 as a negative regulator of NF-κB pathways. TNF-induced TRAF1 upregulation was blocked by the proteasome inhibitor MG-132. Transfection/overexpression, NF-κB reporter assays, pharmacological inhibition FEBS letters Medium 10544244
2008 TRAF1 is required for 4-1BB-mediated CD8 T cell survival in vivo; TRAF1-deficient CD8 T cells fail to activate ERK downstream of 4-1BB, show reduced Bcl-xL upregulation and elevated Bim, resulting in impaired survival during viral infection. ERK inhibition downstream of 4-1BB in wild-type cells phenocopies TRAF1 deficiency. TRAF1-KO mice, viral infection models, intracellular signaling assays (ERK activation), Bcl-xL/Bim Western blot, pharmacological ERK inhibition Journal of immunology High 18523273
2012 TRAF1 is required for maximal classical NF-κB activation downstream of 4-1BB; TRAF1 also restricts constitutive NIK activity in activated T cells by participating in the cIAP1/2:TRAF2:TRAF3:NIK complex. 4-1BB stimulation induces cIAP1-dependent TRAF3 degradation to activate the alternative NF-κB pathway, and this requires TRAF1. siRNA knockdown of NIK, TRAF1-KO primary T cells, NF-κB pathway reporter assays, Western blot for NIK/TRAF3/cIAP The Journal of biological chemistry High 22570473
2013 Increased neuronal TRAF1 after stroke correlates with elevated neuronal death and enlarged ischemic lesions; TRAF1 deficiency is neuroprotective. TRAF1 directly interacts with ASK1 to activate the JNK pro-death pathway and inhibit the Akt survival pathway. Genetic KO/overexpression in mouse stroke model, co-immunoprecipitation for TRAF1-ASK1 interaction, JNK and Akt pathway Western blots Nature communications High 24284943
2016 TRAF1 promotes hepatic steatosis, insulin resistance, and inflammation through enhancing ASK1-mediated P38/JNK cascade activation; ASK1 inhibition abolishes these effects. Demonstrated using TRAF1-KO and liver-specific TRAF1 overexpression mice. Global TRAF1 KO and liver-specific overexpression mouse models, HFD/ob-ob obesity models, in vivo ASK1 inhibitor treatment, P38/JNK pathway Western blots Journal of hepatology High 26860405
2016 The TRAF1 MATH domain binds directly to three LUBAC components (SHARPIN, HOIP, HOIL-1), interfering with NEMO linear ubiquitination and thereby decreasing NF-κB activation and cytokine production independently of TNF. This negative regulation of TLR signaling is distinct from its TNFR superfamily role. Direct binding assays, co-immunoprecipitation of TRAF1-LUBAC complex, NEMO ubiquitination assays, Traf1-KO mice in LPS septic shock model Nature immunology High 27893701
2015 LMP1 TES1 domain signaling induces TRAF1 association with LUBAC and stimulates M1-linked polyubiquitin chain attachment to TRAF1 complexes; TRAF2 (but not cIAP1/2) is required for LUBAC recruitment. LMP1/TRAF1 complexes are also decorated by K63-linked polyubiquitin chains, and TRAF2 is a K63-Ub chain target. TRAF1 depletion markedly impairs LCL growth. Proteomic analysis of immunopurified TRAF1 complexes, M1/K63 polyubiquitin chain detection, TRAF1/HOIP knockdown with proliferation assays PLoS pathogens High 25996949
2006 TRAF1 interacts with the TIR domain adaptor TRIF via its TRAF-C domain; overexpression of TRAF1 inhibits TRIF- and TLR3-mediated NF-κB, ISRE, and IFN-β promoter activation. TRIF overexpression causes caspase-dependent cleavage of TRAF1; the cleaved N-terminal fragment (but not C-terminal) mediates inhibition, and mutation of the caspase cleavage site abolishes inhibition. Yeast two-hybrid, co-immunoprecipitation, domain mapping, NF-κB/ISRE/IFN-β reporter assays, caspase cleavage mutants European journal of immunology Medium 16323247
2003 TRAF1 critically regulates TRAF2-dependent JNK activation downstream of LMP1 TRAF-binding domain in a cell-type-specific manner; in TRAF1-negative epithelial cells reconstitution of TRAF1 expression restores LMP1-induced JNK activation. This TRAF1 requirement is specific to LMP1's TRAF-binding domain and is not shared by CD40's homologous region. TRAF1-positive vs -negative cell lines, TRAF1 reconstitution, dominant-negative TRAF constructs, JNK kinase assays Journal of virology Medium 12502848
2008 PKN1 phosphorylates TRAF1 in vitro and in vivo; this phosphorylation is required to attenuate constitutive IKK/JNK activity in unstimulated cells. Mutation of the TRAF1 phospho-acceptor residue abrogates PKN1-dependent TRAF1 recruitment to TNFR2. The stoichiometric ratio of TRAF1:TRAF2 heteromeric complexes at TNFR2 controls tonic JNK and IKK activity. In vitro kinase assay with PKN1 and TRAF1, in vivo phosphorylation analysis, phospho-acceptor mutagenesis, co-immunoprecipitation with TNFR2, IKK/JNK activity assays Genes to cells Medium 18429822
2004 Phorbol ester-mediated TRAF1 induction in colon cancer cells proceeds through a Ca²⁺-dependent PKC/Raf-1/MEK/ERK/NF-κB pathway; site-specific mutagenesis of NF-κB sites in the TRAF1 promoter (especially the most proximal site) significantly decreases phorbol ester-driven TRAF1 transcription. PKC inhibitors, MEK/ERK inhibitors, dominant-negative Raf-1 transfection, NF-κB site mutagenesis in TRAF1 promoter-reporter constructs Oncogene Medium 14981539
1997 Overexpression of TRAF1 in transgenic mice inhibits antigen-induced apoptosis of CD8⁺ T lymphocytes, establishing a biological role for TRAF1 as a regulator of apoptotic signals downstream of TNFR2. TRAF1 transgenic mice, antigen-induced apoptosis assay in CD8 T cells The Journal of experimental medicine Medium 9151703
2005 TRAF1 associates with NIP45 (NFAT-interacting protein) in the cytoplasm and prevents its nuclear translocation; TRAF1-deficient T cells show elevated nuclear NIP45 and increased Th2 cytokine production, indicating TRAF1 limits Th2 differentiation by retaining NIP45 in the cytoplasm. TRAF1-KO mouse model, Th2 cytokine measurement, subcellular fractionation/nuclear NIP45 Western blot, in vitro T cell stimulation International immunology Medium 16352630
2000 CD40 engagement induces TRAF1 gene transcription in B lymphocytes through two enhancer regions: an upstream region (~2 kb from start site) containing a single critical NF-κB site (mutation abolishes CD40-driven TRAF1 transcription) and an intronic enhancer (between exons 5 and 6) with NF-κB and AP-1 sites. CD40 ligation, reporter gene assays, NF-κB/AP-1 site mutagenesis, B lymphocyte transfections Molecular immunology Medium 11395135
2016 Crystal structure of the TRAF1 TRAF domain (TRAF-N coiled-coil + TRAF-C) reveals that the TRAF-N coiled-coil domain is critical for trimer formation and protein stability; conserved TRAF-C surface residues constitute binding hotspots for interaction with signaling molecules. X-ray crystallography, biochemical trimer formation assays Scientific reports Medium 27151821
2017 Crystal structure of TRAF1 TRAF domain in complex with TANK peptide shows TANK binds TRAF1 using the minor consensus motif Px(Q/E)xT; quantitative binding experiments show TANK interacts with TRAF1 and TRAF2 with similar micromolar affinity. X-ray crystallography (PDB: 5H10), quantitative binding assays FEBS letters Medium 28155233
2018 TRAF1 is critical for solar UV-induced ERK5 phosphorylation and AP-1 (c-Fos/c-Jun) expression in skin carcinogenesis; TRAF1 enhances ubiquitination of ERK5 on lysine 184, which is necessary for ERK5 kinase activity. TRAF1-KO mice show significant inhibition of skin tumor formation. TRAF1-KO mouse carcinogenesis model, ERK5 ubiquitination assays, phosphorylation/AP-1 Western blots, site-specific ubiquitin acceptor mutagenesis The Journal of investigative dermatology Medium 28131816
2018 TRAF1 affects TRAF2-mediated K48-linked ubiquitination of BRAF; loss of TRAF1 decelerated tumor invasion in a urethane-induced lung carcinogenesis model, positioning TRAF1 as a regulator of the BRAF/MEK/ERK signaling pathway in NSCLC. TRAF1 overexpression/knockdown in cancer cells, ubiquitination assays for BRAF, in vivo lung carcinogenesis mouse model Cancer research Medium 29748372
2010 TRAF1 interacts with IKK2 (identified by yeast two-hybrid using IKK2 C-terminal aa 466–756 as bait, binding TRAF1 N-terminal aa 1–228); confirmed by mammalian two-hybrid and co-immunoprecipitation. TRAF1 can both activate and inhibit IKK2 and NF-κB depending on dose; TRAF1 affects TRAF2 clustering in a dose-dependent manner. Yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation, NF-κB reporter assays, fluorescence-tagged co-expression PloS one Medium 20856938
2010 TRAF1 deficiency in TRAF1⁻/⁻/LDLR⁻/⁻ mice attenuates atherosclerosis; mechanistically, TRAF1 deficiency in endothelial cells and monocytes reduces cell adhesion, actin polymerization, CD29 expression, and ICAM-1/VCAM-1 expression. Bone marrow transplantation reveals contributions from both hematopoietic and vascular resident TRAF1. Double-KO mouse atherosclerosis model, bone marrow transplantation, static/dynamic adhesion assays, siRNA in human cells Circulation Medium 20421522
2010 TRAF1 mRNA translation is regulated by an IRES element located within 572 nt upstream of the AUG start codon (critical element between nt −392 and −322); vincristine induces TRAF1 protein expression by regulating cytoplasmic localization of polypyrimidine tract binding protein to stimulate IRES-dependent translation. Reporter assays with IRES-containing 5'-UTR constructs, deletion mapping, polypyrimidine tract binding protein cytoplasmic localization assays Nucleic acids research Medium 20413583
2013 A novel TRAF1-ALK fusion transcript (TRAF1 exon 6 fused to ALK exon 20) was identified in an anaplastic large cell lymphoma patient; the fusion protein was confirmed by Western blot, indicating TRAF1 can function as an ALK fusion partner driving lymphoma. Deep RNA sequencing, Sanger sequencing confirmation, Western blot for fusion protein Genes, chromosomes & cancer Medium 23999969
2007 TRAF1 deficiency in endothelial cells enhances CD40L-induced IL-6 and MCP-1 expression, while TRAF2 and TRAF5 deficiency inhibit CD40L-inducible IL-6 but not MCP-1, demonstrating that TRAF1 has a negative regulatory role in CD40 signaling in endothelial cells. Endothelial cells from TRAF-1, -2, -5-deficient mice, cytokine ELISA, gene silencing in human ECs Arteriosclerosis, thrombosis, and vascular biology Medium 17332487
2014 DNMT3L forms a complex with DNMT3B and NF-κB p65 that controls DNA methylation at the TRAF1 promoter; TET3 is involved in demethylation of TRAF1, demonstrating dynamic methylation control of the TRAF1 locus. TF array binding assays, co-immunoprecipitation of DNMT3L/DNMT3B/p65 complex, bisulfite sequencing of TRAF1 promoter, TET3 functional assays Biochimie Medium 24952347
2011 TGF-β induces posttranslational loss of TRAF1 protein from CD8 T cells, while IL-7 restores TRAF1 levels; loss of TRAF1 correlates with desensitization of 4-1BB signaling and T cell exhaustion during chronic LCMV infection. Transfer of TRAF1⁺ but not TRAF1⁻ memory T cells reduces viral load. Cytokine treatment of primary T cells with TRAF1 Western blot, LCMV chronic infection model, adoptive T cell transfer The Journal of experimental medicine Medium 22184633

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science (New York, N.Y.) 2440 9733516
2007 TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study. The New England journal of medicine 675 17804836
1996 Association of TRAF1, TRAF2, and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation: role in NF-kappaB activation. Molecular and cellular biology 424 8943365
1996 The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. Proceedings of the National Academy of Sciences of the United States of America 369 8692885
2007 A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. PLoS medicine 223 17880261
1997 Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Molecular and cellular biology 185 9032281
2010 Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation. Molecular cell 174 20385093
2001 TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice. Immunity 158 11672546
1997 Characterization of LMP-1's association with TRAF1, TRAF2, and TRAF3. Journal of virology 146 9151858
1999 The human tumor necrosis factor (TNF) receptor-associated factor 1 gene (TRAF1) is up-regulated by cytokines of the TNF ligand family and modulates TNF-induced activation of NF-kappaB and c-Jun N-terminal kinase. The Journal of biological chemistry 144 10383449
2008 ERK-dependent Bim modulation downstream of the 4-1BB-TRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo. Journal of immunology (Baltimore, Md. : 1950) 133 18523273
2002 Regulation of the subcellular localization of tumor necrosis factor receptor-associated factor (TRAF)2 by TRAF1 reveals mechanisms of TRAF2 signaling. The Journal of experimental medicine 119 12370254
1997 A regulatory role for TRAF1 in antigen-induced apoptosis of T cells. The Journal of experimental medicine 116 9151703
2016 Targeting hepatic TRAF1-ASK1 signaling to improve inflammation, insulin resistance, and hepatic steatosis. Journal of hepatology 115 26860405
2013 TRAF1 is a critical regulator of cerebral ischaemia-reperfusion injury and neuronal death. Nature communications 105 24284943
2003 Discrete functions of TRAF1 and TRAF2 in Drosophila melanogaster mediated by c-Jun N-terminal kinase and NF-kappaB-dependent signaling pathways. Molecular and cellular biology 98 14585960
2022 N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma. Molecular cancer 93 35538475
2007 TRAF-1, -2, -3, -5, and -6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 93 17332487
2018 TRAF1 Signaling in Human Health and Disease. Frontiers in immunology 88 30619326
1997 Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily. Biochemical and biophysical research communications 86 9168896
2012 Opposing roles for TRAF1 in the alternative versus classical NF-κB pathway in T cells. The Journal of biological chemistry 80 22570473
2008 STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians. Genes and immunity 80 18432273
1999 TRAF1 is a TNF inducible regulator of NF-kappaB activation. FEBS letters 77 10544244
2006 The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF-kappaB activation independently of TRAF1 AND TRAF2. The Journal of biological chemistry 75 16891304
2015 TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation. PLoS pathogens 70 25996949
2012 Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus. Arthritis and rheumatism 70 21905002
2008 Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid arthritis in a genetically homogeneous population. Human immunology 70 18625278
2004 Regulation of phorbol ester-mediated TRAF1 induction in human colon cancer cells through a PKC/RAF/ERK/NF-kappaB-dependent pathway. Oncogene 69 14981539
2015 A genetic study on C5-TRAF1 and progression of joint damage in rheumatoid arthritis. Arthritis research & therapy 67 25566937
1996 Tumor necrosis factor receptor-associated factor (TRAF)-1, TRAF-2, and TRAF-3 interact in vivo with the CD30 cytoplasmic domain; TRAF-2 mediates CD30-induced nuclear factor kappa B activation. Proceedings of the National Academy of Sciences of the United States of America 64 8943059
2016 The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease. Nature immunology 63 27893701
2000 TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis. The Journal of biological chemistry 61 11098060
2000 Caspase-induced inactivation of the anti-apoptotic TRAF1 during Fas ligand-mediated apoptosis. FEBS letters 60 10692572
2010 Tumor necrosis factor receptor-associated factor 1 (TRAF1) deficiency attenuates atherosclerosis in mice by impairing monocyte recruitment to the vessel wall. Circulation 57 20421522
2003 TRAF1 is a critical regulator of JNK signaling by the TRAF-binding domain of the Epstein-Barr virus-encoded latent infection membrane protein 1 but not CD40. Journal of virology 57 12502848
2011 Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection. The Journal of experimental medicine 56 22184633
2015 A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels. Genes and immunity 53 26673966
2007 Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. The American journal of surgical pathology 52 17197926
2009 The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases. Annals of the rheumatic diseases 50 19433411
2006 TNF receptor-associated factor-1 (TRAF1) negatively regulates Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-mediated signaling. European journal of immunology 50 16323247
2021 DNMT1-induced miR-378a-3p silencing promotes angiogenesis via the NF-κB signaling pathway by targeting TRAF1 in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 49 34749775
2009 TRAF1 is involved in the classical NF-kappaB activation and CD30-induced alternative activity in Hodgkin's lymphoma cells. Molecular immunology 48 19540595
2021 RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-κB and MAPK signaling pathways. Oncogene 47 34759347
2018 TRAF1 Is Critical for Regulating the BRAF/MEK/ERK Pathway in Non-Small Cell Lung Carcinogenesis. Cancer research 46 29748372
2013 Novel TRAF1-ALK fusion identified by deep RNA sequencing of anaplastic large cell lymphoma. Genes, chromosomes & cancer 45 23999969
2007 TRAF1 and its biological functions. Advances in experimental medicine and biology 45 17633014
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
2019 TRAF1 Exacerbates Myocardial Ischemia Reperfusion Injury via ASK1-JNK/p38 Signaling. Journal of the American Heart Association 43 31650881
2008 The TRAF1/C5 region is a risk factor for polyarthritis in juvenile idiopathic arthritis. Annals of the rheumatic diseases 43 18593758
2003 Differential expression and function of A20 and TRAF1 in Hodgkin lymphoma and anaplastic large cell lymphoma and their induction by CD30 stimulation. The Journal of pathology 43 12754742
2014 TRAF1 is a key mediator for hepatic ischemia/reperfusion injury. Cell death & disease 42 25321474
2007 NF-kappaB2 mutation targets TRAF1 to induce lymphomagenesis. Blood 42 17405906
2000 Tumor necrosis factor-alpha-induced lung cell expression of antiapoptotic genes TRAF1 and cIAP2. American journal of respiratory cell and molecular biology 41 10657935
2002 TRAF1: lord without a RING. Science's STKE : signal transduction knowledge environment 40 12023442
2014 A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation. Leukemia 39 25533804
2011 TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated with genetic susceptibility to systemic lupus erythematosus in Turkey. Human immunology 39 21968398
2009 Association of the TRAF1/C5 locus with increased mortality, particularly from malignancy or sepsis, in patients with rheumatoid arthritis. Arthritis and rheumatism 38 19116907
2005 TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas. The American journal of surgical pathology 38 15644776
2017 TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer. Oncoimmunology 37 30524877
2003 Caspase-mediated cleavage converts the tumor necrosis factor (TNF) receptor-associated factor (TRAF)-1 from a selective modulator of TNF receptor signaling to a general inhibitor of NF-kappaB activation. The Journal of biological chemistry 36 12709429
2009 Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese. Annals of the rheumatic diseases 35 19336421
2008 Negative regulation of constitutive NF-kappaB and JNK signaling by PKN1-mediated phosphorylation of TRAF1. Genes to cells : devoted to molecular & cellular mechanisms 35 18429822
2019 4-1BB Regulates Effector CD8 T Cell Accumulation in the Lung Tissue through a TRAF1-, mTOR-, and Antigen-Dependent Mechanism to Enhance Tissue-Resident Memory T Cell Formation during Respiratory Influenza Infection. Journal of immunology (Baltimore, Md. : 1950) 33 30867239
2016 Crystal structure of TRAF1 TRAF domain and its implications in the TRAF1-mediated intracellular signaling pathway. Scientific reports 33 27151821
2017 TXNDC5 is a cervical tumor susceptibility gene that stimulates cell migration, vasculogenic mimicry and angiogenesis by down-regulating SERPINF1 and TRAF1 expression. Oncotarget 31 29207620
2014 DNMT3L interacts with transcription factors to target DNMT3L/DNMT3B to specific DNA sequences: role of the DNMT3L/DNMT3B/p65-NFκB complex in the (de-)methylation of TRAF1. Biochimie 30 24952347
2017 Genome-wide DNA methylation analysis of articular chondrocytes identifies TRAF1, CTGF, and CX3CL1 genes as hypomethylated in osteoarthritis. Clinical rheumatology 29 28470428
2000 Inhibited neutrophil apoptosis: proteasome dependent NF-kappaB translocation is required for TRAF-1 synthesis. Shock (Augusta, Ga.) 28 11028545
2005 TRAF1 regulates Th2 differentiation, allergic inflammation and nuclear localization of the Th2 transcription factor, NIP45. International immunology 27 16352630
2011 Influence of TRAF1/C5 and STAT4 genes polymorphisms on susceptibility and severity of rheumatoid arthritis in Egyptian population. Cellular immunology 26 22196377
2010 Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. PloS one 25 20856938
2001 Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death. Biochemical and biophysical research communications 25 11181075
2010 Lack of association of PTPN22, STAT4 and TRAF1/C5 gene polymorphisms with cardiovascular risk in rheumatoid arthritis. Clinical and experimental rheumatology 24 20822712
2023 Elabela inhibits TRAF1/NF-κB induced oxidative DNA damage to promote diabetic foot ulcer wound healing. iScience 23 37664606
2021 SPION-MSCs enhance therapeutic efficacy in sepsis by regulating MSC-expressed TRAF1-dependent macrophage polarization. Stem cell research & therapy 23 34627385
2012 Patient samples of renal cell carcinoma show reduced expression of TRAF1 compared with normal kidney and functional studies in vitro indicate TRAF1 promotes apoptosis: potential for targeted therapy. Pathology 23 22810054
2009 Susceptibility variants for rheumatoid arthritis in the TRAF1-C5 and 6q23 loci: a meta-analysis. Annals of the rheumatic diseases 23 19401279
2001 Dynamic expression of Drosophila TRAF1 during embryogenesis and larval development. Mechanisms of development 23 11118894
2007 TRAF1 regulates recruitment of lymphocytes and, to a lesser extent, neutrophils, myeloid dendritic cells and monocytes to the lung airways following lipopolysaccharide inhalation. Immunology 21 17328785
2007 Differential expression of TRAF1 aids in the distinction of cutaneous CD30-positive lymphoproliferations. The Journal of investigative dermatology 21 17392826
2022 FXR1 can bind with the CFIm25/CFIm68 complex and promote the progression of urothelial carcinoma of the bladder by stabilizing TRAF1 mRNA. Cell death & disease 20 35194031
2018 Curcumin Attenuates Inflammation in a Severe Acute Pancreatitis Animal Model by Regulating TRAF1/ASK1 Signaling. Medical science monitor : international medical journal of experimental and clinical research 20 29657313
2016 The Upregulation of TRAF1 Induced by Helicobacter pylori Plays an Antiapoptotic Effect on the Infected Cells. Helicobacter 20 27060717
2018 According to Hepatitis C Virus (HCV) Infection Stage, Interleukin-7 Plus 4-1BB Triggering Alone or Combined with PD-1 Blockade Increases TRAF1low HCV-Specific CD8+ Cell Reactivity. Journal of virology 19 29093082
2009 The TRAF1/C5 locus confers risk for familial and severe alopecia areata. The British journal of dermatology 19 20030635
2003 Epstein-Barr virus encoded latent membrane protein 1 (LMP1) and TNF receptor associated factors (TRAF): colocalisation of LMP1 and TRAF1 in primary EBV infection and in EBV associated Hodgkin lymphoma. Molecular pathology : MP 19 12782762
2013 Association study of TRAF1/C5 polymorphism (rs10818488) with susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Gene 18 23321589
2000 Identification and characterization of two CD40-inducible enhancers in the mouse TRAF1 gene locus. Molecular immunology 18 11395135
1997 Organization of the human tumour necrosis factor receptor-associated factor 1 (TRAF1) gene and mapping to chromosome 9q33-34. Gene 18 9300817
2020 PRDX1 is a Tumor Suppressor for Nasopharyngeal Carcinoma by Inhibiting PI3K/AKT/TRAF1 Signaling. OncoTargets and therapy 17 32982301
2020 TRAF1 suppresses antifungal immunity through CXCL1-mediated neutrophil recruitment during Candida albicans intradermal infection. Cell communication and signaling : CCS 16 32093731
2018 Mir-483 inhibits colon cancer cell proliferation and migration by targeting TRAF1. The Kaohsiung journal of medical sciences 16 30173777
2017 TRAF1 Is Critical for DMBA/Solar UVR-Induced Skin Carcinogenesis. The Journal of investigative dermatology 16 28131816
1999 Structure of the murine TRAF1 gene. Molecular immunology 16 10499814
2018 miR-214 Down-Regulation Promoted Hypoxia/Reoxygenation-Induced Hepatocyte Apoptosis Through TRAF1/ASK1/JNK Pathway. Digestive diseases and sciences 15 30560327
2017 Molecular basis for TANK recognition by TRAF1 revealed by the crystal structure of TRAF1/TANK complex. FEBS letters 15 28155233
2013 A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis. Clinical and experimental rheumatology 15 24321457
2012 Associations between TNFSF4 and TRAF1-C5 gene polymorphisms and systemic lupus erythematosus: a meta-analysis. Human immunology 15 22820624
2016 Association of the polymorphisms of TRAF1 (rs10818488) and TNFAIP3 (rs2230926) with rheumatoid arthritis and systemic lupus erythematosus and their relationship to disease activity among Egyptian patients. Central-European journal of immunology 14 27536202
2010 Translation of TRAF1 is regulated by IRES-dependent mechanism and stimulated by vincristine. Nucleic acids research 14 20413583

Missed literature

Know a paper Affinage missed for TRAF1? Flag it for the maintainers and the community.

No submissions yet.