Affinage

TRAF1

TNF receptor-associated factor 1 · UniProt Q13077

Length
416 aa
Mass
46.2 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRAF1 is an NF-κB–inducible adaptor protein that lacks the RING finger domain present in other TRAF family members and functions as a context-dependent modulator of TNF receptor superfamily, Toll-like receptor, and stress kinase signaling. TRAF1 forms TRAF1:(TRAF2)₂ heterotrimers that enhance cIAP2 recruitment, regulate TRAF2 subcellular localization and stability at lipid rafts, and modulate NF-κB activation downstream of TNFR2, CD40, 4-1BB, and CD30 (PMID:20385093, PMID:12370254, PMID:11672546, PMID:18523273). TRAF1 recruits LUBAC to dampen NEMO linear ubiquitination and NF-κB activation in TLR signaling, interacts with ASK1 to promote JNK/p38 pro-death cascades in ischemia and metabolic disease, and is cleaved by caspase-8 at Asp163 to generate a dominant-negative fragment that inhibits IKK-dependent NF-κB activation and amplifies apoptosis (PMID:27893701, PMID:24284943, PMID:11098060, PMID:12709429). TRAF1 expression is transcriptionally driven by NF-κB binding to its promoter and translationally regulated via a 5′-UTR IRES element, establishing feedback circuits that tune inflammatory and survival signaling (PMID:10383449, PMID:9733516, PMID:20413583).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Establishing that TRAF1 forms heterocomplexes with TRAF2 and recruits the NF-κB inhibitor A20, revealing TRAF1 as a scaffold for negative feedback in NF-κB signaling rather than a simple signal transducer.

    Evidence Reciprocal Co-IP with mutagenesis and NF-κB reporter assays in transfected cells; EBV LMP1 cytoplasmic domain dissection identified the PXQXT/S TRAF-binding motif

    PMID:8692885 PMID:8943365

    Open questions at the time
    • No structural basis for TRAF1-TRAF2 heterotrimerization at this stage
    • Stoichiometry of heterocomplex unknown
    • In vivo relevance of A20 recruitment via TRAF1 not tested
  2. 1997 High

    Demonstrating in vivo that TRAF1 overexpression inhibits antigen-induced CD8 T cell apoptosis and that TRAF1/TRAF2 activate NF-κB through CD30 domain 2, placing TRAF1 as a costimulatory adaptor for TNFR superfamily members.

    Evidence Transgenic mouse CD8 T cell apoptosis assay; CD30 cytoplasmic domain mutagenesis with NF-κB reporters

    PMID:9032281 PMID:9151703

    Open questions at the time
    • Receptor-specific versus general anti-apoptotic role not distinguished
    • Endogenous TRAF1 loss-of-function not yet tested
  3. 1998 High

    Identifying TRAF1 as a direct NF-κB transcriptional target that cooperates with TRAF2/cIAP1/cIAP2 to suppress caspase-8, establishing the NF-κB → TRAF1 anti-apoptotic feedback loop.

    Evidence Cotransfection/reporter assays with dominant-negative constructs and NF-κB inhibition, apoptosis readout in TNF-stimulated cells

    PMID:9733516

    Open questions at the time
    • Mechanism of caspase-8 suppression by TRAF1 not defined
    • Relative contribution of TRAF1 vs cIAP1/2 unresolved
  4. 1999 High

    Mapping NF-κB binding sites in the TRAF1 promoter and showing that TRAF1 overexpression prolongs JNK activation while inhibiting NF-κB, revealing TRAF1 as a pathway-selective feedback regulator.

    Evidence EMSA, promoter-luciferase reporters, RNase protection assays, JNK/NF-κB activation with TRAF1 overexpression/deletion constructs

    PMID:10383449 PMID:10544244

    Open questions at the time
    • Mechanism by which TRAF1 prolongs JNK while restraining NF-κB not resolved
    • Overexpression artifacts cannot be excluded for NF-κB inhibition
  5. 2000 High

    Discovering that caspase-8 cleaves TRAF1 at Asp163 during death receptor signaling, generating a C-terminal dominant-negative fragment that blocks NF-κB and amplifies apoptosis — converting TRAF1 from protector to pro-death effector.

    Evidence In vitro caspase cleavage assays, site-directed mutagenesis of LEVD163, overexpression of fragments with NF-κB and apoptosis readouts

    PMID:10692572 PMID:11098060

    Open questions at the time
    • Physiological stoichiometry of cleavage fragments unclear
    • Whether caspase-8 cleavage of TRAF1 is required for apoptosis in vivo untested
  6. 2001 High

    TRAF1 knockout mice revealed that TRAF1 is a negative regulator of TNFR2 signaling in vivo: TRAF1-deficient T cells hyper-respond to TNF via TNFR2, and skin shows TNF hypersensitivity, settling the question of whether TRAF1 is predominantly pro-survival or inhibitory.

    Evidence TRAF1-/- mouse generation, T cell proliferation/NF-κB/AP-1 assays, skin TNF necrosis challenge

    PMID:11672546

    Open questions at the time
    • Whether TRAF1 loss affects TNFR1 signaling in vivo remains unclear
    • Cell-type-specific versus systemic contributions not dissected
  7. 2002 High

    Resolving how TRAF1 modulates TRAF2 function: TRAF1 displaces TRAF2 and CD40 from lipid rafts and prevents TRAF2 degradation, sustaining prolonged signaling — explaining the paradox of TRAF1 acting as both positive and negative regulator depending on signal duration.

    Evidence Lipid raft fractionation in TRAF1-/- dendritic cells, RING finger mutants, JNK and NF-κB time-course assays

    PMID:12370254

    Open questions at the time
    • Whether raft displacement is direct or mediated by another factor unknown
    • Kinetics of TRAF2 stabilization by TRAF1 not quantified
  8. 2003 Medium

    Identifying the IKK complex as a direct target of caspase-cleaved TRAF1: the C-terminal fragment inhibits IKK activation, while full-length TRAF1 constitutively associates with IKK2 via its N-TRAF domain, mechanistically explaining how cleavage switches TRAF1 function.

    Evidence Co-IP of TRAF1 with IKK complex, kinase assays, fragment overexpression with NF-κB reporters

    PMID:12709429

    Open questions at the time
    • Endogenous cleavage fragment–IKK interaction not demonstrated
    • Structural basis for N-TRAF domain–IKK2 interaction unknown
  9. 2008 High

    Establishing TRAF1 as essential for 4-1BB costimulatory signaling in CD8 T cells: TRAF1 is required for ERK activation, Bcl-xL upregulation, and survival during viral infection, and PKN1 phosphorylation of TRAF1 controls its recruitment to TNFR2.

    Evidence TRAF1-/- mice with viral infection model and 4-1BB ligation; in vitro/in vivo kinase assays with phospho-site mutagenesis for PKN1–TRAF1

    PMID:18429822 PMID:18523273

    Open questions at the time
    • PKN1 phosphorylation site on TRAF1 not mapped to a specific residue in the publication
    • Whether PKN1 regulation of TRAF1 applies to 4-1BB pathway untested
  10. 2010 High

    Structural resolution of TRAF1:(TRAF2)₂:cIAP2 complex showed that TRAF1 forms a 1:2 heterotrimer with TRAF2 that enhances cIAP2 binding, providing the atomic basis for TRAF1's modulatory role; concurrently, TRAF1 was shown to regulate atherosclerosis through monocyte-endothelial adhesion and to undergo IRES-dependent translation.

    Evidence X-ray crystallography with mutagenesis (TRAF1:TRAF2:cIAP2); TRAF1-/-/LDLR-/- mouse atherosclerosis model with bone marrow chimeras; bicistronic IRES reporter assays with deletion mapping

    PMID:20385093 PMID:20413583 PMID:20421522

    Open questions at the time
    • Full-length TRAF1:TRAF2 complex structure not available
    • IRES trans-acting factors beyond PTB not identified
    • Whether TRAF1:TRAF2 stoichiometry changes in vivo during signaling unknown
  11. 2012 High

    Demonstrating that TRAF1 has opposing roles in classical versus alternative NF-κB: it promotes classical NF-κB via 4-1BB but restricts constitutive NIK activation by participating in the cIAP1/2:TRAF2:TRAF3:NIK degradation complex, unifying apparently contradictory phenotypes.

    Evidence TRAF1-/- T cells, NIK siRNA rescue, 4-1BB stimulation with cIAP1-dependent TRAF3 degradation assays

    PMID:22570473

    Open questions at the time
    • Direct biochemical demonstration of TRAF1 within the NIK degradation complex lacking
    • Whether TRAF1's role in alternative NF-κB extends beyond T cells unknown
  12. 2013 High

    Revealing a non-immune function: TRAF1 directly binds ASK1 and promotes neuronal apoptosis after ischemia by activating JNK and inhibiting Akt, expanding TRAF1's role beyond immune signaling to stress-induced cell death.

    Evidence Co-IP of TRAF1-ASK1, TRAF1-/- and transgenic mice in stroke model, JNK/Akt pathway assays

    PMID:24284943

    Open questions at the time
    • Whether TRAF1 activates ASK1 directly or relieves thioredoxin inhibition unknown
    • Structural basis for TRAF1-ASK1 interaction not determined
  13. 2015 High

    Demonstrating that TRAF1 serves as a platform for LUBAC recruitment in EBV LMP1 signaling, leading to M1- and K63-linked ubiquitination of TRAF1 complexes and recruitment of NEMO, A20, and ABIN1 — connecting TRAF1 to linear ubiquitin-dependent signaling.

    Evidence Proteomic analysis of immunopurified TRAF1 complexes, ubiquitin linkage-specific antibodies, shRNA knockdown with LCL growth assays

    PMID:25996949

    Open questions at the time
    • Whether TRAF1 is itself a direct ubiquitination substrate or scaffold for other substrates not resolved
    • LUBAC recruitment mechanism (direct vs TRAF2-mediated) debated
  14. 2016 High

    Establishing TRAF1 as a direct negative regulator of TLR/LUBAC signaling independent of TNF: the TRAF1 MATH domain binds SHARPIN, HOIP, and HOIL-1 to block NEMO linear ubiquitination and NF-κB activation; TRAF1-/- mice are hypersusceptible to LPS septic shock.

    Evidence Direct binding assays of TRAF1 MATH domain with LUBAC components, Co-IP, TRAF1-/- mouse LPS challenge, human monocyte disease-SNP validation

    PMID:27893701

    Open questions at the time
    • Whether TRAF1-LUBAC interaction is competitive or allosteric not defined
    • Role of TRAF1 in other TLR pathways beyond TLR4 not explored
  15. 2016 High

    Extending TRAF1-ASK1 axis to metabolic disease: TRAF1 promotes hepatic steatosis through ASK1-p38/JNK activation, and ASK1 inhibition fully rescues TRAF1-driven insulin resistance and lipid accumulation.

    Evidence Global TRAF1-/- and liver-specific transgenic mice on HFD/ob/ob background, ASK1 pharmacological inhibitor rescue

    PMID:26860405

    Open questions at the time
    • Direct phosphorylation or activation mechanism of ASK1 by TRAF1 not defined
    • Whether TRAF1-ASK1 interaction in liver involves TRAF2 not tested
  16. 2017 High

    Crystal structures of TRAF1 TRAF domain alone and in complex with TANK peptide confirmed the Px(Q/E)xT binding motif and showed similar affinity to TRAF2, providing the first structural framework for receptor/adaptor selectivity.

    Evidence X-ray crystallography with quantitative binding measurements

    PMID:27151821 PMID:28155233

    Open questions at the time
    • No structure of full-length TRAF1
    • How TRAF1 distinguishes between different receptor cytoplasmic tails structurally unclear
  17. 2019 Medium

    Extending TRAF1-ASK1 pro-death axis to cardiac ischemia/reperfusion injury, and establishing TRAF1-dependent mTOR activation downstream of 4-1BB for tissue-resident memory CD8 T cell formation in the lung.

    Evidence TRAF1-/- mouse cardiac I/R model with cardiomyocyte overexpression; TRAF1-/- mice in influenza prime-boost model with rapamycin

    PMID:30867239 PMID:31650881

    Open questions at the time
    • Whether TRAF1-mTOR link is direct or mediated through ERK/PI3K unknown
    • Cardiac TRAF1-ASK1 mechanism largely inferred from hepatic/neuronal models

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of full-length TRAF1 and how it differs from other TRAFs lacking the RING domain; the molecular mechanism by which TRAF1 activates ASK1; the relative contributions of TRAF1-LUBAC versus TRAF1-TRAF2 complexes to receptor-specific NF-κB regulation; and whether post-translational modifications beyond PKN1 phosphorylation and caspase cleavage control TRAF1 switching between pro-survival and pro-death functions.
  • No full-length TRAF1 structure available
  • Mechanism of ASK1 activation by TRAF1 not biochemically defined
  • Comprehensive post-translational modification map of TRAF1 lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-5357801 Programmed Cell Death 5 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3
Partners
BIRC3MAP3K5PKN1RBCK1RNF31SHARPINTNFAIP3TRAF2
Complex memberships
TRAF1:(TRAF2)2:cIAP2 heterotrimerTRAF1:LUBAC complexcIAP1/2:TRAF2:TRAF3:NIK repressor complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NF-κB transcriptional activation induces TRAF1 (along with TRAF2, c-IAP1, c-IAP2) gene expression, and these proteins cooperatively suppress caspase-8 activation downstream of TNF-α, blocking TNF-induced apoptosis. Cotransfection/reporter assays, dominant-negative constructs, NF-κB inhibition with functional apoptosis readout Science High 9733516
1996 TRAF1 and TRAF2 interact with A20 (zinc finger protein) via A20's N-terminal domain binding to the conserved C-terminal TRAF domain of TRAF1/TRAF2; this recruits A20 to the TRAF2-TRAF1 complex, and A20's C-terminal zinc finger domain then inhibits NF-κB activation, providing negative feedback. Coimmunoprecipitation, mutational analysis, cotransfection NF-κB reporter assays Proceedings of the National Academy of Sciences High 8692885
1996 TRAF1, TRAF2, and TRAF3 associate with EBV LMP1 at a single cytoplasmic site (aa 199–214), and TRAF1 forms heterocomplexes with TRAF2; TRAF1 uniquely coactivates NF-κB with LMP1(1-231), TRAF1/TRAF2 heteroaggregates mediate NF-κB activation, while TRAF3 negatively modulates it. A PXQXT/S motif was identified as the core TRAF-binding sequence. Coimmunoprecipitation, alanine/deletion mutagenesis, cotransfection NF-κB reporter assays, EBV-transformed B cell biochemistry Molecular and Cellular Biology High 8943365
2010 Crystal structures of TRAF2:cIAP2 and TRAF1:TRAF2:cIAP2 complexes revealed that a TRAF2 trimer binds one cIAP2; TRAF1 preferentially forms a TRAF1:(TRAF2)2 heterotrimer that binds cIAP2 more strongly than TRAF2 alone; TRAF1 itself binds cIAP2 very weakly; key interface residues were 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 by proliferation and NF-κB/AP-1 activation via TNFR2 (but not TNFR1), and skin is hypersensitive to TNF-induced necrosis, demonstrating TRAF1 is a negative regulator of TNFR2-mediated TNF signaling. Knockout mouse generation, T cell functional assays, skin TNF challenge in vivo Immunity High 11672546
2002 TRAF1 regulates subcellular localization of TRAF2: upon CD40 engagement, TRAF2 translocates to lipid rafts in a RING finger-dependent manner, but TRAF1 displaces TRAF2 and CD40 from raft fractions while sustaining prolonged TRAF2 signaling. TRAF1-/- dendritic cells show increased TRAF2 degradation and attenuated secondary signaling responses. Lipid raft fractionation, TRAF1-/- dendritic cell functional assays, RING finger mutants, JNK and NF-κB activation assays The Journal of Experimental Medicine High 12370254
1997 TRAF1 overexpression in transgenic mice inhibits antigen-induced apoptosis of CD8+ T lymphocytes, demonstrating a biological role for TRAF1 as a regulator of apoptotic signals via TNFR2 signaling complex. Transgenic mouse overexpression, antigen-induced apoptosis assay in CD8 T cells The Journal of Experimental Medicine High 9151703
1997 CD30 cytoplasmic domain contains two TRAF-binding motifs: the membrane-proximal domain 1 activates NF-κB independently of TRAFs, while domain 2 (containing PXQXT-like sequences) binds TRAF1, TRAF2, and TRAF3 and activates NF-κB through TRAF1/TRAF2 but not TRAF3; full-length TRAF3 and dominant-negative TRAF1/TRAF2 inhibit NF-κB through domain 2. Deletion/point mutagenesis of CD30, cotransfection NF-κB reporter assays, dominant-negative TRAFs Molecular and Cellular Biology High 9032281
2000 TRAF1 (but not TRAF2-6) is specifically cleaved by caspase-8 at site 160LEVD163 during TNF-α- and Fas-induced apoptosis, generating a C-terminal fragment that enhances TNF receptor-1-mediated apoptosis and suppresses TRAF2-mediated NF-κB activation by acting as a dominant negative. In vitro caspase cleavage assay, site-directed mutagenesis of cleavage site, overexpression of fragments in HEK293T/HT1080 cells, NF-κB reporter assays, apoptosis assays The Journal of Biological Chemistry High 11098060
2000 Caspase cleavage of TRAF1 after Asp-163 during FasL-induced apoptosis generates a C-terminal dominant-negative fragment that blocks TNF-induced NF-κB activation, creating a pro-apoptotic amplification loop. FasL apoptosis assay, identification of cleavage site, dominant-negative functional assay FEBS Letters Medium 10692572
1999 TRAF1 expression is transcriptionally induced by NF-κB binding to three functional sites in the TRAF1 promoter downstream of TNF-R1, CD40, and IL-1R signaling. Overexpression of TRAF1 prolongs TNF-induced JNK activation, while a deletion mutant interferes with both NF-κB and JNK activation, indicating TRAF1 participates in feedback regulation. EMSA, promoter-luciferase reporter assays, RNase protection assays, TRAF1 overexpression/deletion constructs with JNK/NF-κB activation readouts The Journal of Biological Chemistry High 10383449
1999 TRAF1 overexpression in HEK293T cells prevents NF-κB activation by TNF, IL-1, TRAF2, and TRAF6, identifying TRAF1 as a TNF-inducible negative regulator of NF-κB signaling; TNF-induced TRAF1 upregulation was blocked by proteasome inhibitor MG-132. NF-κB reporter assays, Western blot, pharmacological inhibition FEBS Letters Medium 10544244
2008 TRAF1 is required for survival signaling downstream of 4-1BB in CD8 T cells during viral infection in vivo: TRAF1-deficient CD8 T cells fail to activate ERK in response to 4-1BB ligation, leading to impaired Bcl-xL upregulation and increased Bim levels; ERK inhibition downstream of 4-1BB in wild-type cells phenocopies TRAF1 loss. TRAF1-/- mice, viral infection model (in vivo), 4-1BB ligation assays, ERK inhibitor, Bcl-xL/Bim Western blots Journal of Immunology High 18523273
2012 TRAF1 plays opposing roles in NF-κB pathways in T cells: it is required for maximal classical NF-κB activation downstream of 4-1BB, but also restricts constitutive NIK (NF-κB-inducing kinase) activation in anti-CD3-activated T cells, limiting alternative NF-κB pathway activity. TRAF1 participates in the cIAP1/2:TRAF2:TRAF3:NIK repressor complex; 4-1BB stimulation induces cIAP1-dependent TRAF3 degradation to activate alternative NF-κB. TRAF1-/- T cells, siRNA knockdown of NIK, 4-1BB stimulation assays, cIAP1-dependent TRAF3 degradation assays The Journal of Biological Chemistry High 22570473
2016 TRAF1 MATH domain directly binds to three components of the linear ubiquitin chain assembly complex (LUBAC) — SHARPIN, HOIP, and HOIL-1 — to interfere with NEMO recruitment and linear ubiquitination, thereby decreasing NF-κB activation and cytokine production in response to LPS/TLR signaling, independently of TNF. TRAF1-/- mice show increased susceptibility to LPS-induced septic shock. Direct binding assay (TRAF1 MATH domain), coimmunoprecipitation, Traf1-/- mouse LPS challenge, cytokine measurements in human monocytes with disease-associated SNP Nature Immunology High 27893701
2015 LMP1 TES1 domain signaling induces association of TRAF1 with LUBAC complex and stimulates linear (M1)-linked and K63-linked polyubiquitin chain attachment to TRAF1 complexes; TRAF2 (not cIAP1/2) is critical for LUBAC recruitment to TRAF1; M1-ubiquitin binding proteins NEMO, A20, and ABIN1 associate with TRAF1 in LMP1-expressing cells. Depletion of TRAF1 or HOIP impairs LCL growth. Proteomic analysis of immunopurified TRAF1 complexes, ubiquitin linkage-specific antibodies, shRNA knockdown, LCL growth assays PLoS Pathogens High 25996949
2016 Crystal structure of the TRAF1 TRAF domain (containing both TRAF-N coiled-coil and TRAF-C domains) was solved; the TRAF-N coiled-coil domain is critical for trimer formation and stability; conserved surface residues on TRAF-C domain are binding hot spots for signaling molecule interactions. X-ray crystallography, structural analysis Scientific Reports Medium 27151821
2017 Crystal structure of TRAF1 TRAF domain in complex with TANK peptide revealed that TANK binds TRAF1 using the minimal consensus Px(Q/E)xT motif; TANK peptide interacts with both TRAF1 and TRAF2 with similar micromolar affinity. X-ray crystallography, quantitative binding experiments (ITC or SPR implied) FEBS Letters High 28155233
2013 TRAF1 directly interacts with ASK1 (apoptosis signal-regulating kinase 1), and increased neuronal TRAF1 after ischemia promotes neuronal apoptosis by activating the JNK pro-death pathway and inhibiting Akt survival signaling through ASK1. Co-immunoprecipitation (direct TRAF1-ASK1 interaction), TRAF1-/- and TRAF1 transgenic mice, genetic in vivo stroke model, pathway activation assays Nature Communications High 24284943
2016 TRAF1 promotes hepatic steatosis through direct activation of the ASK1-P38/JNK signaling cascade; ASK1 inhibition abrogates the effect of TRAF1 on insulin dysfunction, inflammation, and hepatic lipid accumulation. Global TRAF1-/- and liver-specific TRAF1 transgenic mice, HFD/ob/ob models, ASK1 inhibitor rescue experiments, in vitro palmitate-treated hepatocytes Journal of Hepatology High 26860405
2014 TRAF1 mediates hepatic ischemia/reperfusion injury by activating the ASK1/JNK pro-death pathway and promoting NF-κB-mediated inflammatory responses; TRAF1 deficiency is liver protective, while hepatocyte-specific TRAF1 overexpression aggravates injury. Mouse hepatic I/R model, TRAF1-/- mice, hepatocyte-specific TRAF1 transgenic mice, in vitro hepatocyte assays, pathway activation Western blots Cell Death & Disease High 25321474
2003 The caspase-generated C-terminal TRAF1 fragment (TRAF domain alone) acts as a general inhibitor of NF-κB activation by directly targeting the IKK complex; full-length TRAF1 interacts with IKK2 via its N-TRAF domain and is constitutively associated with the IKK complex; the cleavage product (not full-length TRAF1) inhibits IKK activation. Coimmunoprecipitation of TRAF1 with IKK complex, cotransfection reporter assays, kinase assays, caspase cleavage fragment overexpression The Journal of Biological Chemistry Medium 12709429
2008 PKN1 serine/threonine kinase phosphorylates TRAF1 in vitro and in vivo; this phosphorylation is required for attenuation of constitutive IKK and JNK activity; phosphorylation enables TRAF1 recruitment to TNFR2, and mutagenesis of the phospho-acceptor residue abrogates PKN1-dependent TNFR2 recruitment, establishing PKN1 as a writer for TRAF1 phosphorylation. In vitro kinase assay, in vivo phosphorylation, site-directed mutagenesis, IKK/JNK activity assays, TNFR2 coimmunoprecipitation Genes to Cells High 18429822
2001 Caspase-cleaved TRAF1 C-terminal fragment coimmunoprecipitates with TRAF2 released from the TNF-R1 complex during prolonged TNF treatment, sequestering TRAF2 and rendering cells sensitive to TNF-induced apoptosis. Coimmunoprecipitation of cleaved TRAF1 with TRAF2, TNF stimulation time course, apoptosis assays Biochemical and Biophysical Research Communications Medium 11181075
2006 TRAF1 interacts with TRIF (via TRAF-C domain of TRAF1 and TIR domain of TRIF) and negatively regulates TRIF/TLR3-mediated NF-κB and IFN-β activation; TRIF-induced caspase-dependent cleavage of TRAF1 generates an N-terminal fragment that mediates the inhibitory effect; caspase cleavage site mutation or caspase inhibitor abolishes TRAF1-mediated TRIF signaling inhibition. Yeast two-hybrid identification, coimmunoprecipitation, mutagenesis, overexpression reporter assays, caspase inhibitor experiments European Journal of Immunology Medium 16323247
2005 TRAF1 associates with NIP45 (NFAT-interacting protein) in the cytoplasm and prevents its translocation to the nucleus, thereby limiting Th2 cytokine (IL-4) transcription; TRAF1-/- T cells have elevated nuclear NIP45 and produce more Th2 cytokines. TRAF1-/- T cells, cytokine assays, biochemical fractionation showing TRAF1-NIP45 cytoplasmic association, T cell transfer in vivo model International Immunology Medium 16352630
2010 TRAF1 interacts with IKK2 (N-terminal aa 1-228 of TRAF1 binds C-terminal aa 466-756 of IKK2); coexpression of TRAF1 and TRAF2 at different ratios affects TRAF2 clustering and NF-κB activity in a dose-dependent manner, suggesting TRAF1:TRAF2 stoichiometry regulates NF-κB. Yeast two-hybrid, mammalian two-hybrid, coimmunoprecipitation, fluorescence imaging of TRAF2 clustering, NF-κB reporter assays PLoS One Medium 20856938
2007 NF-κB2 mutant p80HT binds the TRAF1 promoter in vivo (chromatin immunoprecipitation) and activates TRAF1 transcription; elevated TRAF1 mediates the anti-apoptotic activity of p80HT, as TRAF1 knockdown abrogates p80HT-mediated anti-apoptosis and restores B cell homeostasis in p80HT transgenic mice. Transgenic mouse model, ChIP, siRNA knockdown of TRAF1, apoptosis assays, TRAF1 and p80HT double-mutant genetic analysis Blood High 17405906
2013 A novel TRAF1-ALK fusion protein (Exon 6 of TRAF1 fused to Exon 20 of ALK) was identified by deep RNA sequencing in ALCL; the fusion transcript was confirmed by Sanger sequencing and the fusion protein visualized by Western blot, resulting in cytoplasmic ALK localization. Deep RNA sequencing, Sanger sequencing confirmation, Western blot Genes, Chromosomes & Cancer Medium 23999969
2018 TRAF1 regulates the BRAF/MEK/ERK signaling pathway in non-small cell lung cancer by affecting TRAF2-mediated Lys48-linked ubiquitination of BRAF; loss of TRAF1 decelerates tumor invasion in a urethane-induced lung carcinogenesis model. TRAF1-/- mouse lung carcinogenesis model, ubiquitination assays (Lys48-linked), BRAF/MEK/ERK pathway activation assays Cancer Research Medium 29748372
2017 TRAF1 is required for solar UV-induced ERK5 phosphorylation and AP-1 (c-Fos/c-Jun) activation; TRAF1 expression enhances ubiquitination of ERK5 on Lys184, which is necessary for ERK5 kinase activity; TRAF1-/- mice show significant inhibition of UV-induced skin tumor formation. TRAF1-/- mouse skin carcinogenesis model, ERK5 ubiquitination assay at Lys184, ERK5 kinase activity assays, AP-1 reporter assays Journal of Investigative Dermatology Medium 28131816
2003 TRAF1 is a critical regulator of JNK/AP-1 signaling downstream of LMP1 TES1 domain in TRAF1-positive lymphoma cells; JNK activation by LMP1 TES1 is blocked by dominant-negative TRAF2 but not TRAF5, and requires TRAF1 reconstitution in TRAF1-negative epithelial cells. This TRAF1 role is specific to LMP1 TES1 and not to CD40 or LMP1 TRADD-interacting domain. Dominant-negative TRAF constructs, TRAF1-negative vs TRAF1-positive cell lines, TRAF1 reconstitution, JNK activation assays Journal of Virology Medium 12502848
2010 TRAF1 deficiency in both hematopoietic and vascular resident cells attenuates atherosclerosis by impairing monocyte adhesion to endothelium; TRAF1-/- endothelial cells and monocytes show reduced adhesion molecule expression (ICAM-1, VCAM-1), reduced actin polymerization, and reduced CD29 expression. TRAF1-/-/LDLR-/- mouse atherosclerosis model, bone marrow transplantation, static/dynamic adhesion assays, siRNA in human cells Circulation High 20421522
2010 TRAF1 mRNA translation is regulated by an internal ribosome entry segment (IRES) in its unusually long 5'-UTR (element located between nt -392 and -322 is essential); the chemotherapeutic drug vincristine induces TRAF1 expression by regulating cytoplasmic localization of polypyrimidine tract binding protein, stimulating IRES-dependent translation. Bicistronic reporter assays, deletion mapping of IRES, vincristine treatment, PTB localization assays Nucleic Acids Research Medium 20413583
2019 TRAF1 promotes myocardial ischemia/reperfusion injury by activating ASK1-mediated JNK/p38 MAPK cascades; TRAF1-/- mice are protected from I/R-induced cardiac dysfunction, inflammation, and cardiomyocyte death, while TRAF1 overexpression in primary cardiomyocytes enhances hypoxia/reoxygenation-induced apoptosis and inflammation. TRAF1-/- mouse I/R model, primary cardiomyocyte overexpression, ASK1-JNK/p38 pathway Western blots Journal of the American Heart Association Medium 31650881
2019 4-1BB-induced accumulation of CD8 effector T cells in the lung and formation of tissue-resident memory T cells requires TRAF1 and mTOR (rapamycin-sensitive); both Ag and costimulation must be delivered locally, demonstrating TRAF1-dependent mTOR pathway activation downstream of 4-1BB in effector T cell persistence. TRAF1-/- mice, influenza infection/prime-boost model, rapamycin treatment, intratracheal 4-1BB stimulation, lung T cell quantification Journal of Immunology Medium 30867239
2011 TRAF1 is specifically lost from virus-specific CD8 T cells during chronic HIV/LCMV infection; TGF-β induces posttranslational loss of TRAF1, while IL-7 restores TRAF1 levels; TRAF1 is required for the effect of combination IL-7/anti-4-1BB therapy in reducing viral load. Human HIV patient samples, LCMV mouse model, TRAF1 knockdown in viral controllers, TGF-β/IL-7 treatment, adoptive transfer of TRAF1+ vs TRAF1- memory T cells The Journal of Experimental Medicine High 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.) 2437 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 422 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 173 20385093
2001 TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice. Immunity 156 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
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