Affinage

TRAF4

TNF receptor-associated factor 4 · UniProt Q9BUZ4

Length
470 aa
Mass
53.5 kDa
Annotated
2026-06-10
100 papers in source corpus 55 papers cited in narrative 55 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRAF4 is a multifunctional scaffold and RING-domain E3 ubiquitin ligase that couples diverse cell-surface receptors to downstream kinase and transcriptional outputs, acting at the crossroads of growth-factor, cytokine, innate-immune, and morphogenetic signaling (PMID:23973329, PMID:29715200, PMID:30352854). A recurring theme is non-degradative ubiquitination as an activating signal: TRAF4 catalyzes K27-, K29-, and K63-linked chains on receptor and effector substrates—boosting TrkA kinase activity (PMID:29715200), potentiating IRS-1 coupling to IGF1R (PMID:33991522), directing androgen-receptor genomic redistribution toward FOXA1/HOXB13 loci (PMID:37155905), priming CHK1 for ATR-dependent activation after DNA damage (PMID:32357935), and licensing LAMTOR1-dependent mTORC1 activation in response to amino acids (PMID:38229144). In TGF-β signaling TRAF4 is recruited to the activated receptor, antagonizes the E3 ligase SMURF2 and recruits the deubiquitinase USP15 to stabilize TβRI, and undergoes K63-linked auto-ubiquitination to activate TAK1, amplifying both SMAD and non-SMAD outputs (PMID:23973329). This SMURF2-antagonism logic recurs broadly: TRAF4 ubiquitinates and degrades SMURF2 to drive osteogenic differentiation (PMID:31076633) and to stabilize HER2 (PMID:35864174), and degrades SMURF1 to enhance BMP/SMAD signaling (PMID:35731212). TRAF4 also acts as a deubiquitinase-blocking scaffold, binding USP7/HAUSP and USP10 to exclude p53 and destabilize it independently of catalytic activity (PMID:23388826, PMID:30940456). Through its TRAF domain it directly engages the EGFR juxtamembrane segment to promote asymmetric dimerization and kinase activation (PMID:30352854), scaffolds NADPH oxidase via phospho-p47phox to spatially direct ROS production and MAPK activation (PMID:15743827, PMID:12023963), and binds phosphoinositides to localize to tight junctions and drive Rac1-dependent migration (PMID:23760265, PMID:24311986). In innate immunity TRAF4 is largely a negative regulator, restraining TLR, NOD2, and TLR7-type I IFN signaling through interactions with p47phox, NOD2, and a PACSIN1/TRAF6 complex (PMID:16052631, PMID:21097508, PMID:36622335). Its subcellular partitioning and activity are tuned by post-translational modifications, including Smurf1-mediated K190 ubiquitination directing tight-junction localization (PMID:23760265), IKKα phosphorylation at S426 (PMID:22547678), and AKT-mediated S242 phosphorylation that promotes 14-3-3θ binding and nuclear translocation toward c-Jun (PMID:39716976). TRAF4 is itself a p53/p63 transcriptional target, embedding it in feedback circuits during DNA-damage and proliferative responses (PMID:12788948, PMID:18087216).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 Low

    Established TRAF4's first receptor associations, distinguishing it from other TRAFs by selective binding to LTβR and weakly p75NGFR rather than the classic TNFR1/2/Fas/CD40 set.

    Evidence In vitro cytoplasmic-domain binding assays and immunofluorescence in transfected cells

    PMID:9626059

    Open questions at the time
    • in vitro binding only with no functional consequence established
    • no downstream signaling readout for the LTβR interaction
  2. 2002 Medium

    Defined the TRAF domain as the module that mediates p47phox binding and cell-contact localization, linking TRAF4 to NADPH oxidase-dependent ROS and JNK activation.

    Evidence Yeast two-hybrid, domain deletion, dominant-negative ROS/JNK assays; GFP-fusion localization and NF-κB pathway epistasis in KO Jurkat lines

    PMID:12023963 PMID:12354113

    Open questions at the time
    • physiological NADPH oxidase context inferred from overexpression
    • nuclear vs cytoplasmic localization control not fully resolved
  3. 2005 High

    Showed TRAF4 acts both as a positive scaffold for receptor-driven ROS/MAPK (p47phox membrane translocation) and as a silencer of innate-immune signaling, foreshadowing its context-dependent duality.

    Evidence Reciprocal Co-IP, siRNA knockdown, membrane fractionation, NADPH oxidase and ERK assays in endothelium; luciferase reporters for NF-κB/IFN-β; MEKK4 oligomerization/kinase assays

    PMID:15743827 PMID:16052631 PMID:16157600

    Open questions at the time
    • how the same protein toggles between positive and negative roles not defined
    • direct enzymatic activity not yet demonstrated
  4. 2013 High

    Crystallized the TRAF4 oligomerization scaffold and showed it binds phosphoinositides and undergoes Smurf1-directed K190 ubiquitination, establishing how lipid binding and modification target TRAF4 to tight junctions to control Rac1-dependent migration.

    Evidence Crystal structures of the TRAF/coiled-coil domain, lipid-binding and PIP-residue mutagenesis, K190R analysis, Rac1 and migration assays

    PMID:23760265 PMID:24311986 PMID:24419373

    Open questions at the time
    • precise PIP species and membrane geometry in vivo not defined
    • how K190 ubiquitination is read out for localization unclear
  5. 2013 High

    Reframed TRAF4 as a TGF-β receptor amplifier by antagonizing SMURF2, recruiting USP15 to stabilize TβRI, and self-activating via K63 auto-ubiquitination of TAK1—a logic later seen across multiple SMURF substrates.

    Evidence Reciprocal Co-IP, ubiquitination assays, siRNA, EMT/migration assays, breast cancer xenografts; parallel HAUSP/USP7 competition and p53-promoter studies

    PMID:12788948 PMID:23388826 PMID:23973329

    Open questions at the time
    • direct vs scaffold contribution to TAK1 activation not fully separated
    • stoichiometry of USP15 vs SMURF2 at the receptor unresolved
  6. 2018 High

    Defined TRAF4 as a bona fide E3 ligase that activates substrates through non-degradative chains and as a direct EGFR-dimerization factor, unifying its catalytic and scaffold functions on receptor tyrosine kinases.

    Evidence In vitro ubiquitination reconstitution with substrate-site mutagenesis (TrkA K27/K29), kinase/invasion assays; NMR mapping of EGFR juxtamembrane binding with mutagenesis and proliferation readouts

    PMID:29715200 PMID:30352854

    Open questions at the time
    • determinants of chain-type selectivity (K27 vs K29 vs K63) not defined
    • how ubiquitination mechanistically increases kinase activity unclear
  7. 2020 High

    Extended the activating-ubiquitination paradigm to the DNA-damage and metabolic machinery, showing TRAF4 primes CHK1 for ATR activation and links to chemoresistance.

    Evidence Mass-spec interaction mapping, in vitro/in vivo ubiquitination, K132R mutagenesis, CHK1 phosphorylation and xenograft chemosensitivity assays

    PMID:32357935

    Open questions at the time
    • how K63-CHK1 ubiquitination enables ATR phosphorylation mechanistically unclear
    • upstream signal recruiting TRAF4 to CHK1 not identified
  8. 2021 High

    Demonstrated TRAF4 can also direct K48-linked degradative ubiquitination (PPARγ) and is itself controlled by m6A RNA modification, showing both catalytic versatility and layered upstream regulation.

    Evidence Co-IP, ubiquitination/proteasome assays, m6A-RIP, ALKBH5/YTHDF1 axis, adipogenesis assays; parallel IRS-1 K29 ubiquitination study

    PMID:33880847 PMID:33991522

    Open questions at the time
    • what dictates degradative vs non-degradative outcome for different substrates
    • tissue-specificity of m6A control of TRAF4 not generalized
  9. 2023 High

    Connected TRAF4 ubiquitination to transcriptional reprogramming, with K27-ubiquitinated androgen receptor redistributing to FOXA1/HOXB13 loci, and to amino-acid-sensing via LAMTOR1/mTORC1.

    Evidence In vitro/in vivo ubiquitination, ChIP-seq, site mutagenesis, mTORC1/Rag GTPase binding assays, knock-in cells

    PMID:37155905 PMID:38229144

    Open questions at the time
    • how ubiquitination of AR alters cofactor selection mechanistically unclear
    • integration of mTORC1 input with other TRAF4 outputs unknown
  10. 2024 Medium

    Established a phosphorylation-driven nuclear program in which AKT-mediated S242 phosphorylation promotes 14-3-3θ binding, nuclear translocation, and c-Jun-dependent IL-8 transcription, defining a localization switch for TRAF4 function.

    Evidence Co-IP with domain mapping, S242 phosphorylation assays, nuclear fractionation, IL-8 promoter reporters, KO-rescue and xenografts

    PMID:39716976

    Open questions at the time
    • balance between cytoplasmic scaffold and nuclear transcriptional roles not quantified
    • generality of the S242/14-3-3θ switch beyond this context unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular features determine TRAF4's substrate selection and chain-type output, and how its catalytic, deubiquitinase-blocking, and lipid/receptor-scaffolding modes are coordinated within a single cell.
  • no unifying structural model of substrate/chain-type specificity
  • no systematic map of which functions dominate in which tissue
  • interplay of competing modifications (K190 Ub, S426 and S242 phospho) on the same molecule undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3
Partners
AKTEGFRGPIBΒMEKK4NOD2P47PHOXSMURF2USP7
Complex memberships
HER2-TRAF4-SMURF2 complexNADPH oxidase (NOX2/NOX4-p47phox) complexPACSIN1-TRAF4-TRAF6 complex

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Upon TGF-β stimulation, TRAF4 is recruited to the active TGF-β receptor complex where it antagonizes E3 ligase SMURF2 and facilitates recruitment of deubiquitinase USP15 to TβRI, stabilizing TβRI on the plasma membrane. TGF-β receptor-TRAF4 interaction also triggers K63-linked TRAF4 polyubiquitylation and subsequent activation of TAK1, enhancing both SMAD and non-SMAD TGF-β signaling. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, cell migration and EMT assays, breast cancer metastasis xenograft model Molecular cell High 23973329
2015 IL-17 signaling activates a novel cascade via IL-17R-Act1-TRAF4-MEKK3-ERK5 to directly stimulate keratinocyte proliferation and tumor formation; TRAF4 acts downstream of Act1 in this pathway, and p63 (a transcription factor induced by this axis) drives a positive feedback loop by transcriptionally upregulating TRAF4 expression. Genetic epistasis (Traf4-/- cells/mice), luciferase reporter assays for TRAF4 promoter, kinase pathway analysis, keratinocyte proliferation and tumor formation assays The Journal of experimental medicine High 26347473
2005 TRAF4 binds the phosphorylated form of NADPH oxidase subunit p47phox in a PKC-dependent manner; upon TNF-α stimulation, p47phox phosphorylation increases p47phox-TRAF4 association, membrane translocation of the complex, and NADPH oxidase activation; TRAF4 knockdown inhibits TNF-α-induced ERK1/2 activation without affecting p47phox phosphorylation or p22phox binding. Co-immunoprecipitation, siRNA knockdown, membrane fractionation, NADPH oxidase activity assay, ERK1/2 phosphorylation assay in endothelial cells Molecular and cellular biology High 15743827
2013 TRAF4 is required for K63-linked ubiquitination and activation of Akt in lung cancer cells; TRAF4 attenuation impairs Akt activation and downstream glucose metabolism (Glut1 and HK2 expression), and inhibits anchorage-independent growth and xenograft tumor development. RNAi knockdown, ubiquitination assays, xenograft mouse model, glucose metabolism assays Cancer research Medium 24154876
2002 TRAF4 and p47phox interact via a tail-to-tail interaction between the C-terminus of p47phox and the conserved TRAF domain of TRAF4; coexpression of both proteins synergistically increases oxidant production and JNK activation; expression of the p47phox-binding domain of TRAF4 blocks endothelial JNK activation by TNFα and HIV-1 Tat. Yeast two-hybrid screen, domain deletion analysis, overexpression/dominant-negative experiments, JNK activation assays, ROS measurement The Journal of biological chemistry Medium 12023963
2005 TRAF4 physically interacts with p47phox and functionally counteracts TRAF6 and TRIF to suppress TLR-mediated NF-κB and IFN-β promoter activation, acting as a silencer of TLR signaling. Co-immunoprecipitation, luciferase reporter assays for NF-κB and IFN-β promoter, functional TLR signaling assays European journal of immunology Medium 16052631
2018 TRAF4 acts as an E3 ubiquitin ligase that promotes K27- and K29-linked ubiquitination at the TrkA (NGF receptor) kinase domain, increasing TrkA kinase activity and tyrosine autophosphorylation; mutation of TRAF4-targeted ubiquitination sites abolishes TrkA autophosphorylation and interaction with downstream proteins; this mechanism drives prostate cancer metastasis. Co-immunoprecipitation, in vitro ubiquitination assays, site-directed mutagenesis of ubiquitination sites, kinase activity assays, invasion assays, xenograft model The Journal of clinical investigation High 29715200
2021 TRAF4 acts as an E3 RING ubiquitin ligase that promotes K48-linked ubiquitination and proteasomal degradation of PPARγ, thereby inhibiting adipogenesis; curcumin upregulates TRAF4 via m6A modification (ALKBH5/YTHDF1 axis) to achieve this anti-adipogenic effect. Co-immunoprecipitation, ubiquitination assays, proteasome inhibitor experiments, m6A-RIP, YTHDF1 binding assays, adipogenesis (oil red O) assays in vivo and in vitro EMBO reports High 33880847
2019 TRAF4 acts as an E3 ubiquitin ligase mediating K48-linked ubiquitination of Smurf2 at K119, causing its proteasomal degradation, and thereby positively regulating osteogenic differentiation of mesenchymal stem cells both in vitro and in vivo. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K119R), osteogenic differentiation assays, in vivo MSC implantation model Cell death and differentiation High 31076633
2013 The TRAF domain of TRAF4 binds to the N-terminal TRAF-like region of deubiquitinase HAUSP/USP7 and blocks access of p53 to the same region of HAUSP, leading to loss of p53 deubiquitination and p53 destabilization, thereby conferring resistance to cytotoxic stress. Co-immunoprecipitation, domain-mapping experiments, ubiquitination/deubiquitination assays, lentiviral cDNA rescue screen, breast cancer cell stress assays Genes & development High 23388826
2019 TRAF4 interacts with deubiquitinase USP10 and blocks p53 access to USP10, resulting in p53 destabilization through reduced deubiquitination, independently of TRAF4's E3 ubiquitin ligase activity, promoting fibroblast proliferation in keloids. Co-immunoprecipitation, USP10 knockdown rescue experiments, p53 stability assays, keloid fibroblast proliferation assays The Journal of investigative dermatology Medium 30940456
2013 Smurf1 E3 ligase induces ubiquitination of TRAF4 at K190; this ubiquitination is required for proper localization of TRAF4 to tight junctions in confluent epithelial cells and for TRAF4-dependent Rac1 activation and cell migration. Ubiquitination assays, K190R mutant analysis, immunofluorescence localization, Rac1 activation assay, cell migration assays The Journal of biological chemistry High 23760265
2013 TRAF4 possesses a phosphoinositide (PIP)-binding domain within its TRAF domain; the trimeric TRAF domain binds up to three PIP molecules using basic surface residues; this lipid-binding is required for TRAF4 recruitment to tight junctions, its function as a negative regulator of tight junction stability, and for promoting cell migration. Crystal structure of TRAF4 TRAF domain (structural), lipid-binding assays, mutagenesis of PIP-binding residues, immunofluorescence of tight junction localization, cell migration assays PLoS biology High 24311986
2005 TRAF4 interacts with the kinase domain of MEKK4 (but not requiring MEKK4 kinase activity); coexpression of TRAF4 and MEKK4 synergistically activates JNK; TRAF4 stimulates MEKK4 kinase activity by promoting MEKK4 oligomerization; the TRAF domain of TRAF4 mediates MEKK4 binding. Co-immunoprecipitation of endogenous proteins (K562 cells and embryos), domain-mapping, kinase activity assays, JNK activation assays, chemical dimerization experiments The Journal of biological chemistry High 16157600
2010 TRAF4 directly binds to NOD2 via two consecutive glutamate residues in NOD2; this interaction inhibits NOD2-induced NF-κB activation and NOD2-induced bacterial killing; mutation of these glutamate residues abrogates both TRAF4 binding and its inhibitory function. Co-immunoprecipitation, site-directed mutagenesis of NOD2 binding motif, NF-κB reporter assays, bacterial killing assays The Journal of biological chemistry High 21097508
2012 IKKα phosphorylates TRAF4 at serine-426; this phosphorylation is required for TRAF4-mediated negative regulation of innate immune signaling; TRAF4 binding to NOD2 is required for its phosphorylation by IKKα; serine-426 resides within an exaggerated β-bulge unique to TRAF4 among TRAF proteins. Peptide substrate array, in vitro kinase assay, site-directed mutagenesis (S426A), structural analysis, NF-κB reporter assays, NOD2 interaction studies Molecular and cellular biology High 22547678
2015 TRAF4 is recruited to the IL-25 receptor (IL-17RB) and is required for the ACT1/IL-25R interaction; TRAF4 then recruits E3 ligase SMURF2 to degrade the inhibitory adaptor DAZAP2, which is a prerequisite for IL-25 signaling; TRAF4-deficient mice show blunted airway eosinophilia and Th2 cytokine production in response to IL-25. Co-immunoprecipitation, Traf4-/- mouse model, IL-25 challenge experiments, siRNA knockdown of DAZAP2, ubiquitination/degradation assays Journal of immunology High 25681341
2013 TRAF4 crystal structure of the TRAF domain with coiled-coil domain was solved at 2.3 Å resolution, revealing the structural basis for TRAF4 oligomerization and receptor-effector interactions. X-ray crystallography at 2.3 Å resolution Acta crystallographica. Section D, Biological crystallography High 24419373
2011 In TRAF4-deficient mice, myelin is perturbed in the CNS (disorganized layers, paranode disorganization), Purkinje cells degenerate (confirmed by TUNEL, caspase-3 activation, PARP1 cleavage), and the NgR/p75NTR/RhoA/Rock2 signaling pathway is activated; TRAF4 is expressed by oligodendrocytes at all stages of differentiation. TRAF4-KO mouse analysis, primary cell culture, electron microscopy, immunofluorescence, TUNEL assay, western blotting for apoptotic markers and signaling kinases PloS one Medium 22363515
2011 In Drosophila, Traf4 is required for efficient apical constriction during ventral furrow formation and for proper localization of Armadillo (β-catenin) to the apical position in constricting cells; Traf4 and Armadillo interact physically and functionally; Traf4 acts independently of TNF receptor and JNK signaling in this context. Drosophila genetic analysis (traf4 mutants), immunofluorescence, co-immunoprecipitation, epistasis experiments excluding TNF receptor/JNK involvement Molecular and cellular biology Medium 21986496
2017 In Drosophila glia, TRAF4 is a novel Draper binding partner required for transcriptional reporter activation after axonal injury and for phagocytosis of axonal debris; TRAF4 and Misshapen (MSN) act downstream of Draper to activate JNK signaling in glia, resulting in transcriptional responses dependent on dAP-1 and STAT92E. Co-immunoprecipitation (Draper-TRAF4 interaction), Drosophila genetic analysis (traf4 mutants), axonal injury model, transcriptional reporter assays, phagocytosis assays Nature communications Medium 28165006
2003 TRAF4 is transcriptionally regulated by p53 in response to DNA damage and p53 activation; the murine TRAF4 promoter contains a functional p53 DNA-binding site ~1 kb upstream of the start codon; overexpression of TRAF4 induces apoptosis and suppresses colony formation; TRAF4 localizes to the cytoplasm and remains there following DNA damage. Microarray screen, p53 adenovirus overexpression, temperature-sensitive p53 cell line, promoter reporter assay, colony formation assay, immunofluorescence The Journal of biological chemistry Medium 12788948
2004 TRAF4 augments NF-κB activation triggered by GITR (glucocorticoid-induced TNFR); this requires a previously mapped TRAF-binding site in the cytoplasmic domain of GITR and is inhibited by A20; this is the first functional association of TRAF4 with a TNFR family-triggered signaling pathway. Luciferase NF-κB reporter assays, GITR cytoplasmic domain mutant analysis, A20 inhibition experiments Cellular and molecular life sciences Medium 15583869
2011 TRAF4 selectively binds cytoplasmic sequences of platelet GPIbβ and GPVI as demonstrated by protein array and affinity-binding assays; TRAF4, p47phox, Hic-5, and Pyk2 co-immunoprecipitate with GPIb/GPVI from human platelet lysates; GPIb- and GPVI-selective agonists induce phosphorylation of TRAF4-associated proteins, attenuated by Nox2 inhibition. Protein array analysis, affinity-binding (pulldown) assays, co-immunoprecipitation from human platelets, agonist stimulation experiments Journal of thrombosis and haemostasis Medium 20946164
2017 Crystal structure of TRAF4 (residues 290–470) in complex with GPIbβ peptide (residues 177–181) was solved; the GPIbβ peptide binds to a unique shallow surface with two hydrophobic pockets on TRAF4; a TRAF4-binding motif Arg-Leu-X-Ala was identified, present in platelet receptors and TGF-β receptor. X-ray crystallography (TRAF4–GPIbβ peptide complex), binding motif analysis, mutagenesis validation Proceedings of the National Academy of Sciences of the United States of America High 29073066
2018 TRAF4 directly binds the juxtamembrane (JM) C-terminal segment of EGFR (identified by NMR and structure-based alignment); this binding promotes EGFR asymmetric dimerization and kinase activation; deletion or point mutation of the TRAF4-binding site in EGFR dramatically reduces autophosphorylation and EGF-driven cell proliferation; TRAF4 deficiency attenuates EGFR activation. NMR spectroscopy, structure-based sequence alignment, EGFR deletion and point mutant analysis, autophosphorylation assays, cell proliferation assays Proceedings of the National Academy of Sciences of the United States of America High 30352854
2020 TRAF4 catalyzes K63-linked ubiquitination of CHK1 at K132 following DNA damage; this ubiquitination is required for subsequent CHK1 phosphorylation and activation by ATR; TRAF4 depletion impairs CHK1 activity and sensitizes colorectal cancer cells to fluorouracil and other chemotherapeutic agents in vitro and in vivo. Mass spectrometry identification of CHK1-TRAF4 interaction, in vitro and in vivo ubiquitination assays, site-directed mutagenesis (K132R), CHK1 phosphorylation assays, xenograft model Journal of hematology & oncology High 32357935
2021 TRAF4 promotes K29-linked nonproteolytic ubiquitination of IRS-1 at its C-terminal end, enhancing IGF1-induced IGFR-IRS-1 interaction, IRS-1 tyrosine phosphorylation, and downstream AKT/ERK activation; mutation of IRS-1 ubiquitination sites abolishes these effects and inhibits breast cancer cell proliferation. In vitro ubiquitination assays, site-directed mutagenesis of ubiquitination sites (K29R), Co-immunoprecipitation (IGFR-IRS-1), phosphorylation assays, breast cancer proliferation assays The Journal of biological chemistry High 33991522
2023 TRAF4 mediates K27-linked nonproteolytic ubiquitination of androgen receptor (AR) at its C-terminal tail, increasing AR association with pioneer factor FOXA1 and driving AR binding to distinct genomic loci enriched with FOXA1/HOXB13 motifs, including olfactory receptor genes, boosting intracellular cAMP and E2F activity to promote castration-resistant prostate cancer. In vitro and in vivo ubiquitination assays, ChIP-seq, site-directed mutagenesis of AR ubiquitination sites, Co-immunoprecipitation, gene expression and proliferation assays under androgen deprivation Proceedings of the National Academy of Sciences of the United States of America High 37155905
2022 TRAF4 stabilizes Caveolin-1 (CAV1) by preventing ZNRF1-mediated ubiquitination and facilitating USP7-mediated deubiquitination of CAV1, independently of TRAF4's E3 ligase catalytic activity; TRAF4-mediated CAV1 stabilization activates AKT/ERK1/2 signaling to promote glioblastoma stemness and temozolomide resistance. Co-immunoprecipitation (TRAF4-CAV1-USP7-ZNRF1 interactions), ubiquitination assays, TRAF4 catalytic mutant experiments, AKT/ERK signaling assays, GBM stem cell assays, xenograft model, drug (risperidone) inhibition Cancer research High 35895752
2022 TRAF4 mediates K63-linked ubiquitination of LAMTOR1 at K151, promoting LAMTOR1 binding to Rag GTPases and enhancing mTORC1 activation in response to amino acid availability; K151R knock-in or TRAF4 knockout blocks amino acid-induced mTORC1 activation. Co-immunoprecipitation, in vitro ubiquitination assays, K151R knock-in cells, mTORC1 activity assays, Rag GTPase binding assays, TRAF4-KO cells Advanced science High 38229144
2020 TRAF4 binds PKM2 and activates PKM2 kinase activity, which subsequently activates β-catenin signaling to inhibit MSC adipogenesis; TRAF4 expression during adipogenesis is regulated by ALKBH5-mediated N6-methyladenosine RNA demethylation. Co-immunoprecipitation (TRAF4-PKM2), PKM2 kinase activity assay, β-catenin signaling assay, RNA-binding protein immunoprecipitation (m6A), adipogenesis assays in vitro and in vivo EBioMedicine Medium 32268273
2022 TRAF4 stabilizes SETDB1 by mediating its atypical (non-degradative) ubiquitination via the Tudor domain of SETDB1, maintaining SETDB1 function and thereby promoting AKT pathway activation in glioblastoma; only the Tudor domain of SETDB1 mediates TRAF4 interaction. Co-immunoprecipitation with domain mapping, ubiquitination assays, TRAF4 knockdown, SETDB1 stability assays, AKT pathway analysis International journal of molecular sciences Medium 36077559
2022 Radiation promotes K63-linked ubiquitination and poly-ubiquitination of TRAF4 in normal lung fibroblasts; K63-ubiquitinated TRAF4 forms complexes with NOX2 or NOX4 by mediating phosphorylated p47phox, stabilizing NOX complexes and decreasing their lysosomal degradation, increasing endosomal ROS and NF-κB-mediated ICAM1 upregulation. Ubiquitination assays, Co-immunoprecipitation (TRAF4-NOX2/NOX4 complexes), lysosomal degradation assays, ROS measurement, NF-κB reporter/immunoblot, conditioned media experiments Scientific reports Medium 28827764
2022 In bladder cancer, TRAF4 targets SMURF1 (a negative regulator of BMP/SMAD signaling) for proteasomal degradation, thereby enhancing BMP/SMAD signaling and inhibiting NF-κB signaling and EMT; ERK mediates TRAF4 phosphorylation, reducing TRAF4 protein levels in bladder cancer. TRAF4 overexpression/knockdown, proteasomal degradation assays for SMURF1, transcriptomic analysis, phospho-SMAD1/5 and phospho-NFκB-p65 immunostaining, ERK inhibitor experiments Molecular cancer research Medium 35731212
2019 Cu-dependent binding of antioxidant-1 (Atox1) to TRAF4 promotes Atox1 nuclear translocation in TNF-α-stimulated endothelial cells; TRAF4 depletion inhibits Atox1 nuclear translocation, p47phox expression, ROS production, VCAM1/ICAM1 expression, and monocyte adhesion; Atox1 colocalizes with TRAF4 at the nucleus in inflamed ECs. Nuclear fractionation, en face staining, Co-immunoprecipitation, siRNA knockdown, ROS measurement, VCAM1/ICAM1 expression assays, confocal microscopy American journal of physiology. Cell physiology Medium 31553645
2002 TRAF4-GFP fusion localizes to cytoplasm, while the TRAF domain alone (T4(259-470)) localizes to the nucleus and can recruit full-length TRAF4 into the nucleus; in cells forming cell-cell contacts, TRAF4 is recruited to sites of contact via its C-TRAF domain; TRAF4 mRNA is upregulated by NF-κB activators (TNF, PMA) in a manner dependent on IKKγ/NEMO and (for TNF) on RIP. GFP-fusion constructs with live-cell imaging/immunofluorescence, deletion mutant analysis, NF-κB pathway inhibition experiments (IKKγ-deficient and RIP-deficient Jurkat cells), RT-PCR European journal of biochemistry Medium 12354113
2001 Pim-1 kinase binds and phosphorylates TRAF4-associated factor 2 (TFAF2/SNX6), and this interaction translocates TFAF2/SNX6 from cytoplasm to nucleus; this translocation is not dependent on Pim-1-mediated phosphorylation. Yeast two-hybrid, co-immunoprecipitation, phosphorylation assay, subcellular fractionation/immunofluorescence FEBS letters Low 11591366
2013 TRAF2 interacts with TRAF4 (Co-IP in multiple breast cancer cell lines) and retains TRAF4 in the cytoplasm; TRAF2 depletion by siRNA reduces cytoplasmic TRAF4 and increases nuclear TRAF4 expression; cytoplasmic TRAF4 expression (promoted by TRAF2) augments cell proliferation and NF-κB nuclear expression after TNF-α treatment. Co-immunoprecipitation, siRNA knockdown, immunofluorescence localization, western blotting of cytoplasmic/nuclear fractions Biochemical and biophysical research communications Low 23743189
2015 TRAF4 interacts with PRMT5 via the zinc finger domains of TRAF4; TRAF4 upregulates predominantly nuclear PRMT5 expression, and TRAF4-driven cell proliferation in breast cancer is mainly dependent on PRMT5 nuclear expression. Co-immunoprecipitation, western blotting, nuclear fractionation, domain binding analysis Tumour biology Low 25704480
2020 COX-2 inhibition (celecoxib or siRNA) prevents TGF-β-induced K63-linked ubiquitination of AKT by blocking the interaction between AKT and E3 ubiquitin ligase TRAF4; COX-2 can bind to PDK1/AKT to form a compound; si-COX-2 restrained PDK1 expression and AKT phosphorylation, and prevented TRAF4 recruitment to AKT. Co-immunoprecipitation, siRNA knockdown, ubiquitination assays, AKT phosphorylation assays Redox biology Medium 33152664
2022 TRAF4 promotes K63-linked ubiquitination of AKT following irradiation, activating AKT; active AKT phosphorylates and inactivates GSK3β, reducing MCL-1 phosphorylation at S159 and protecting MCL-1 from JOSD1-dependent ubiquitination/degradation, thereby stabilizing MCL-1 and conferring radioresistance. Co-immunoprecipitation (TRAF4-AKT, MCL-1-JOSD1), ubiquitination assays, phosphorylation assays, MCL-1 stability assays, MCL-1 inhibitor experiments, xenograft model Cell death & disease Medium 36535926
2023 Irradiation activates JNK K63-linked ubiquitination (by TRAF4) and JNK phosphorylation; c-Jun activation then transcriptionally induces Bcl-xL, contributing to radioresistance; TRAF4 knockdown impairs JNK ubiquitination/activation and sensitizes colorectal cancer cells to irradiation. Ubiquitination assays, JNK phosphorylation assays, c-Jun chromatin/reporter assays, Bcl-xL expression assays, TRAF4 knockdown, Bcl-xL inhibitor, xenograft model Cell death & disease Medium 36765039
2022 TRAF4 regulates HER2 stability by forming a membrane-associated complex with HER2 and SMURF2; SMURF2 ubiquitinates HER2 leading to its degradation, while TRAF4 stabilizes HER2 by degrading SMURF2 and inhibiting SMURF2-HER2 binding; TRAF4 knockdown reduces HER2 stability and improves trastuzumab sensitivity. Co-immunoprecipitation (HER2-TRAF4-SMURF2 complex), ubiquitination assays, TRAF4/SMURF2 knockdown, HER2 stability assays, trastuzumab sensitivity assays Oncogene Medium 35864174
2021 TRAF4 is required for CD40-NF-κB signaling in CLL cells; TRAF4 is a direct target of miR-29 family members (miR-29a/b/c); BCR signaling represses miR-29 via MYC, allowing TRAF4 upregulation and stronger CD40-NF-κB activation; BCR inhibitors (ibrutinib, idelalisib) disrupt this loop by restoring miR-29 and reducing TRAF4. miRNA target validation (luciferase reporter, western blot), miR-29 overexpression/inhibition, TRAF4 siRNA knockdown, NF-κB signaling assays, BCR inhibitor treatment Blood Medium 33171493
2024 NGF-stimulated AKT signaling phosphorylates TRAF4 at Ser242, enhancing its interaction with 14-3-3θ and promoting TRAF4 nuclear translocation; in the nucleus, the TRAF domain of TRAF4 interacts with c-Jun and stimulates its transcriptional activity, leading to enhanced IL-8 promoter activity, which mediates nuclear TRAF4-induced tumor stemness and metastatic dormancy. Co-immunoprecipitation (TRAF4-14-3-3θ, TRAF4-c-Jun), phosphorylation assays (S242), nuclear fractionation/localization, promoter reporter assays (IL-8), TRAF4-KO rescue experiments, tumor xenograft models Advanced science Medium 39716976
2023 PACSIN1 forms a trimolecular complex with TRAF4 and TRAF6 that regulates type I IFN production downstream of TLR-7; a Q59K mutation in PACSIN1 decreases binding to TRAF4 while increasing binding to N-WASP, leading to unrestrained TRAF6-mediated IFNβ activation; TRAF4 thus negatively regulates TLR-7-induced type I IFN through this complex. Co-immunoprecipitation (trimolecular complex), CRISPR/Cas9 knock-in/knockout, luciferase reporter assays (IFNβ, NF-κB), siRNA knockdown, immunofluorescence Arthritis & rheumatology Medium 36622335
2022 TRAF4 activates RAC1 and this is required for TGFβ-promoted CD44 cleavage and migration in A549 lung cancer cells; TRAF4 knockdown inhibits CD44-dependent migration, which is rescued by constitutively active RAC1. siRNA knockdown of TRAF4, constitutively active RAC1 rescue, CD44 cleavage assays, migration assays Cancers Medium 33804427
2022 TRAF4 inhibits the interaction between Smurf2 and Eg5, and promotes Smurf2 ubiquitination and degradation via its RING domain, thereby preventing Smurf2-catalyzed Eg5 ubiquitination; the resulting stabilization of Eg5 promotes spindle assembly and breast cancer cell proliferation; TRAF4 interacts with Eg5 via its zinc finger domain. Co-immunoprecipitation with domain mapping, ubiquitination assays (TRAF4 RING domain and zinc finger domain), Eg5 protein stability assays, spindle assembly immunofluorescence, proliferation assays Frontiers in oncology Medium 35692762
2020 TRAF4 impairs LPS-induced autophagy in ankylosing spondylitis MSCs, potentially by inhibiting the phosphorylation of Beclin-1; elevated TRAF4 expression in AS-MSCs accounts for their reduced autophagic response to LPS. Western blotting of autophagy markers (Beclin-1 phosphorylation, LC3), LPS stimulation of MSCs from AS patients vs. healthy donors, TRAF4 expression comparison Experimental & molecular medicine Low 28604663
2007 TAp63 isoforms are the most potent transcriptional activators of TRAF4 among p53 family members; endogenous p63 binds the TRAF4 promoter in vivo (ChIP assay); disrupting p63 expression downregulates TRAF4 mRNA and protein in SCCHN; p73 and p53 also transactivate TRAF4 but less potently than TAp63. ChIP assay for p63 binding to TRAF4 promoter, siRNA knockdown of endogenous p63, luciferase reporter assay (p63/p73/p53 transactivation), RT-PCR and western blotting Cancer biology & therapy Medium 18087216
2015 TRAF4 interacts with p70s6k via its zinc finger domain in MCF7 cells; cytoplasmic TRAF4 activates the p70s6k/S6 signaling pathway in an mTOR-dependent manner, promoting cell proliferation in breast cancer; TRAF2 also promotes p70s6k activation via upregulation of cytoplasmic TRAF4 and plays a critical role in TNFα-induced p70s6k/S6 pathway activation. Co-immunoprecipitation (TRAF4-p70s6k, zinc finger domain mapping), mTOR inhibitor (rapamycin) experiments, p70s6k phosphorylation assays, cell proliferation assays Oncotarget Low 25738361
2020 TRAF4 is a novel substrate of SIAH1 E3 ubiquitin ligase; the TRAF domain of TRAF4 is critical for binding to SIAH1; TRAF4 prevents SIAH1-mediated β-catenin degradation, thereby protecting β-catenin levels and contributing to chemotherapy resistance. Co-immunoprecipitation (TRAF4-SIAH1), domain-mapping (TRAF domain required), β-catenin stability assays, etoposide resistance assays Breast cancer research and treatment Low 32671611
1998 TRAF-4 directly binds the cytosolic domain of lymphotoxin-β receptor (LTβR) and weakly with the p75 nerve growth factor receptor (NGFR) in vitro binding assays, but not with TNFR1, TNFR2, Fas, or CD40; immunofluorescence of transfected cells showed TRAF-4 localizes to cytosol but not nucleus. In vitro binding assays (cytoplasmic domain binding), immunofluorescence of transfected cells The American journal of pathology Low 9626059
2014 TRAF4 directly interacts with Akt and promotes Akt membrane recruitment essential for Akt activation; overexpression of constitutively active Akt rescues cell growth arrest caused by TRAF4 silencing in breast cancer cells. Co-immunoprecipitation (TRAF4-Akt), siRNA knockdown, constitutively active Akt rescue experiment, cell proliferation/migration assays Oncology reports Low 24993240

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis. Molecular cell 211 23973329
2015 A novel IL-17 signaling pathway controlling keratinocyte proliferation and tumorigenesis via the TRAF4-ERK5 axis. The Journal of experimental medicine 192 26347473
2005 Acute tumor necrosis factor alpha signaling via NADPH oxidase in microvascular endothelial cells: role of p47phox phosphorylation and binding to TRAF4. Molecular and cellular biology 180 15743827
2018 Circular RNA‑MTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis. International journal of oncology 113 30015883
2013 TRAF4 is a critical molecule for Akt activation in lung cancer. Cancer research 102 24154876
2002 Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 91 11943846
2005 TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF. European journal of immunology 85 16052631
2021 Curcumin prevents obesity by targeting TRAF4-induced ubiquitylation in m6 A-dependent manner. EMBO reports 83 33880847
2006 TRAF4 overexpression is a common characteristic of human carcinomas. Oncogene 74 16799635
2002 Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase. The Journal of biological chemistry 72 12023963
2000 TRAF4 deficiency leads to tracheal malformation with resulting alterations in air flow to the lungs. The American journal of pathology 71 10934170
2018 TRAF4-mediated ubiquitination of NGF receptor TrkA regulates prostate cancer metastasis. The Journal of clinical investigation 70 29715200
1998 TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues. The American journal of pathology 63 9626059
2017 Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling. Nature communications 61 28165006
2007 TRAF4, the unique family member. Advances in experimental medicine and biology 61 17633017
2019 TRAF4 positively regulates the osteogenic differentiation of mesenchymal stem cells by acting as an E3 ubiquitin ligase to degrade Smurf2. Cell death and differentiation 60 31076633
2011 TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets. Journal of thrombosis and haemostasis : JTH 60 20946164
2021 miR-29 modulates CD40 signaling in chronic lymphocytic leukemia by targeting TRAF4: an axis affected by BCR inhibitors. Blood 59 33171493
2016 Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells. BMC cancer 58 27842582
2010 A novel motif in the Crohn's disease susceptibility protein, NOD2, allows TRAF4 to down-regulate innate immune responses. The Journal of biological chemistry 56 21097508
2020 MIR210HG promotes cell proliferation and invasion by regulating miR-503-5p/TRAF4 axis in cervical cancer. Aging 55 32087604
2003 Identification and characterization of the cytoplasmic protein TRAF4 as a p53-regulated proapoptotic gene. The Journal of biological chemistry 55 12788948
2004 TRAF4 functions as an intermediate of GITR-induced NF-kappaB activation. Cellular and molecular life sciences : CMLS 53 15583869
2020 Silencing COX-2 blocks PDK1/TRAF4-induced AKT activation to inhibit fibrogenesis during skeletal muscle atrophy. Redox biology 52 33152664
2001 Pim-1 translocates sorting nexin 6/TRAF4-associated factor 2 from cytoplasm to nucleus. FEBS letters 48 11591366
2019 TRAF4 Promotes Fibroblast Proliferation in Keloids by Destabilizing p53 via Interacting with the Deubiquitinase USP10. The Journal of investigative dermatology 45 30940456
2013 Ubiquitination of tumor necrosis factor receptor-associated factor 4 (TRAF4) by Smad ubiquitination regulatory factor 1 (Smurf1) regulates motility of breast epithelial and cancer cells. The Journal of biological chemistry 45 23760265
1998 Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development. Mechanisms of development 44 9507120
2013 SRC-3 coactivator regulates cell resistance to cytotoxic stress via TRAF4-mediated p53 destabilization. Genes & development 43 23388826
2005 MEKK4 is an effector of the embryonic TRAF4 for JNK activation. The Journal of biological chemistry 41 16157600
2020 YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4. Cancer cell international 40 32280300
2013 TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration. PLoS biology 40 24311986
2020 TRAF4 acts as a fate checkpoint to regulate the adipogenic differentiation of MSCs by activating PKM2. EBioMedicine 39 32268273
2017 TRAF4 Regulates Migration, Invasion, and Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma. Oncology research 39 28256185
2002 Intracellular localization and transcriptional regulation of tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4). European journal of biochemistry 39 12354113
2022 TRAF4 Maintains Deubiquitination of Caveolin-1 to Drive Glioblastoma Stemness and Temozolomide Resistance. Cancer research 38 35895752
2017 TRAF4 promotes lung cancer aggressiveness by modulating tumor microenvironment in normal fibroblasts. Scientific reports 35 28827764
2015 Proliferative role of TRAF4 in breast cancer by upregulating PRMT5 nuclear expression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 25704480
2015 TRAF4 enhances oral squamous cell carcinoma cell growth, invasion and migration by Wnt-β-catenin signaling pathway. International journal of clinical and experimental pathology 35 26617938
2020 Nonenzymatic function of Aldolase A downregulates miR-145 to promote the Oct4/DUSP4/TRAF4 axis and the acquisition of lung cancer stemness. Cell death & disease 34 32188842
2015 MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4. Oncology reports 33 25976502
2012 In vivo evidence that TRAF4 is required for central nervous system myelin homeostasis. PloS one 33 22363515
2012 IκB kinase α phosphorylation of TRAF4 downregulates innate immune signaling. Molecular and cellular biology 31 22547678
2015 TRAF4-SMURF2-mediated DAZAP2 degradation is critical for IL-25 signaling and allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 30 25681341
2011 Role for Traf4 in polarizing adherens junctions as a prerequisite for efficient cell shape changes. Molecular and cellular biology 29 21986496
2022 LncRNA HCG18 upregulates TRAF4/TRAF5 to facilitate proliferation, migration and EMT of epithelial ovarian cancer by targeting miR-29a/b. Molecular medicine (Cambridge, Mass.) 28 34983361
2020 Ubiquitination of the DNA-damage checkpoint kinase CHK1 by TRAF4 is required for CHK1 activation. Journal of hematology & oncology 28 32357935
2019 Novel interaction of antioxidant-1 with TRAF4: role in inflammatory responses in endothelial cells. American journal of physiology. Cell physiology 27 31553645
2006 Identification and characterization of proteins interacting with Traf4, an enigmatic p53 target. Cancer biology & therapy 27 16969126
2018 The tumor suppressive miR-302c-3p inhibits migration and invasion of hepatocellular carcinoma cells by targeting TRAF4. Journal of Cancer 26 30087710
2008 Characterization of immune functions in TRAF4-deficient mice. Immunology 25 18284467
2022 The Research Progress in Physiological and Pathological Functions of TRAF4. Frontiers in oncology 24 35242717
2022 TRAF4 hyperactivates HER2 signaling and contributes to Trastuzumab resistance in HER2-positive breast cancer. Oncogene 24 35864174
2020 ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4. Bioscience reports 24 32065218
2014 TRAF4 enhances osteosarcoma cell proliferation and invasion by Akt signaling pathway. Oncology research 24 25700355
2018 Down-regulation of TRAF4 targeting RSK4 inhibits proliferation, invasion and metastasis in breast cancer xenografts. Biochemical and biophysical research communications 23 29684350
2013 Different activation of TRAF4 and TRAF6 in inflammatory bowel disease. Mediators of inflammation 23 23431243
2012 Divergent effects of p47(phox) phosphorylation at S303-4 or S379 on tumor necrosis factor-α signaling via TRAF4 and MAPK in endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 23 22460559
2022 Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance. Cell death & disease 21 36535926
2024 TRAF4-Mediated LAMTOR1 Ubiquitination Promotes mTORC1 Activation and Inhibits the Inflammation-Induced Colorectal Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 38229144
2018 MiR-29a Inhibits Glioma Tumorigenesis through a Negative Feedback Loop of TRAF4/Akt Signaling. BioMed research international 20 30186853
2013 TRAF2 regulates the cytoplasmic/nuclear distribution of TRAF4 and its biological function in breast cancer cells. Biochemical and biophysical research communications 20 23743189
2004 Spatial and temporal distribution of the traf4 genes during zebrafish development. Gene expression patterns : GEP 20 15749085
2022 TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling. Molecular cancer research : MCR 19 35731212
2015 TRAF4 promotes the growth and invasion of colon cancer through the Wnt/β-catenin pathway. International journal of clinical and experimental pathology 19 25973026
2013 Structure of the TRAF4 TRAF domain with a coiled-coil domain and its implications for the TRAF4 signalling pathway. Acta crystallographica. Section D, Biological crystallography 19 24419373
2014 TRAF4 participates in Wnt/β-catenin signaling in breast cancer by upregulating β-catenin and mediating its translocation to the nucleus. Molecular and cellular biochemistry 18 24990246
2011 TRAF4, at the Crossroad between Morphogenesis and Cancer. Cancers 18 24212830
2024 TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance. International journal of biological sciences 17 38164179
2023 TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance. Cell death & disease 17 36765039
2018 TRAF4 binds to the juxtamembrane region of EGFR directly and promotes kinase activation. Proceedings of the National Academy of Sciences of the United States of America 17 30352854
2007 TRAF4 is potently induced by TAp63 isoforms and localised according to differentiation in SCCHN. Cancer biology & therapy 17 18087216
2023 De Novo PACSIN1 Gene Variant Found in Childhood Lupus and a Role for PACSIN1/TRAF4 Complex in Toll-like Receptor 7 Activation. Arthritis & rheumatology (Hoboken, N.J.) 16 36622335
2023 TRAF4-mediated nonproteolytic ubiquitination of androgen receptor promotes castration-resistant prostate cancer. Proceedings of the National Academy of Sciences of the United States of America 16 37155905
2014 TRAF4 promotes tumorigenesis of breast cancer through activation of Akt. Oncology reports 16 24993240
2014 TRAF4 mediates activation of TGF-β signaling and is a biomarker for oncogenesis in breast cancer. Science China. Life sciences 16 25249198
2021 Grouper TRAF4, a Novel, CP-Interacting Protein That Promotes Red-Spotted Grouper Nervous Necrosis Virus Replication. International journal of molecular sciences 15 34200212
2017 Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients. Experimental & molecular medicine 15 28604663
2023 SRC-3/TRAF4 facilitates ovarian cancer development by activating the PI3K/AKT signaling pathway. Medical oncology (Northwood, London, England) 13 36625999
2020 TRAF4, a new substrate of SIAH1, participates in chemotherapy resistance of breast cancer cell by counteracting SIAH1-mediated downregulation of β-catenin. Breast cancer research and treatment 13 32671611
2019 RETRACTED: TRAF4 promotes endometrial cancer cell growth and migration by activation of PI3K/AKT/Oct4 signaling. Experimental and molecular pathology 13 30853613
2017 Molecular basis for unique specificity of human TRAF4 for platelets GPIbβ and GPVI. Proceedings of the National Academy of Sciences of the United States of America 13 29073066
2015 Cytoplasmic TRAF4 contributes to the activation of p70s6k signaling pathway in breast cancer. Oncotarget 13 25738361
2022 TRAF4 Inhibits the Apoptosis and Promotes the Proliferation of Breast Cancer Cells by Inhibiting the Ubiquitination of Spindle Assembly-Associated Protein Eg5. Frontiers in oncology 12 35692762
2022 TRAF4 Promotes the Proliferation of Glioblastoma by Stabilizing SETDB1 to Activate the AKT Pathway. International journal of molecular sciences 12 36077559
2021 The E3 ligase TRAF4 promotes IGF signaling by mediating atypical ubiquitination of IRS-1. The Journal of biological chemistry 11 33991522
2024 Nerve Growth Factor Signaling Promotes Nuclear Translocation of TRAF4 to Enhance Tumor Stemness and Metastatic Dormancy Via C-Jun-mediated IL-8 Autocrine. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 39716976
2023 USP7 mediates TRAF4 deubiquitination to facilitate the malignant phenotype of ovarian cancer via the RSK4/PI3K/AKT axis. Journal of cancer research and therapeutics 10 37006049
2022 OTU7B Modulates the Mosquito Immune Response to Beauveria bassiana Infection via Deubiquitination of the Toll Adaptor TRAF4. Microbiology spectrum 9 36537797
2021 TRAF4/6 Is Needed for CD44 Cleavage and Migration via RAC1 Activation. Cancers 9 33804427
2014 The phosphoinositide-binding protein TRAF4 modulates tight junction stability and migration of cancer cells. Tissue barriers 9 25610759
2013 Expression and anti-apoptotic function of TRAF4 in human breast cancer MCF-7 cells. Oncology letters 9 24396457
2022 Overexpression of TRAF4 promotes lung cancer growth and EGFR-dependent phosphorylation of ERK5. FEBS open bio 8 35748027
2022 Novel Findings in Teleost TRAF4, a Protein Acts as an Enhancer in TRIF and TRAF6 Mediated Antiviral and Inflammatory Signaling. Frontiers in immunology 8 35898509
2020 LncRNA SNHG15 regulates osteosarcoma progression in vitro and in vivo via sponging miR-346 and regulating TRAF4 expression. Open life sciences 8 33817231
2014 Knockdown of TRAF4 expression suppresses osteosarcoma cell growth in vitro and in vivo. International journal of molecular medicine 8 25270078
2023 TRAF4 is crucial for ST2+ memory Th2 cell expansion in IL-33-driven airway inflammation. JCI insight 7 37607012
2022 TRAF4 promotes the malignant progression of high-grade serous ovarian cancer by activating YAP pathway. Biochemical and biophysical research communications 7 36029535
2023 An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza. Communications biology 6 37270623
2007 [Expression and significance of TRAF4 protein in breast carcinoma]. Ai zheng = Aizheng = Chinese journal of cancer 6 17927880

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