Affinage

OTUD4

OTU domain-containing protein 4 · UniProt Q01804

Length
1114 aa
Mass
124.0 kDa
Annotated
2026-04-29
35 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTUD4 is an OTU-family deubiquitinase that functions as both a catalytically active enzyme with broad ubiquitin-chain specificity and a non-catalytic scaffold for recruiting other deubiquitinases, thereby regulating innate immune signaling, stress responses, DNA repair, and tumor progression. Its intrinsic K48-directed deubiquitinase activity stabilizes diverse substrates—including MAVS, GSDME, GPX4, SETDB1, CD73, p53, Snail1, EGFR, and others—by preventing their proteasomal degradation (PMID:30410068, PMID:36411454, PMID:40338740, PMID:37739210, PMID:38530357, PMID:41266709, PMID:41730840), while phosphorylation near its catalytic domain, together with an adjacent ubiquitin-interacting motif, switches its specificity toward K63-linked chains, enabling it to deubiquitinate MyD88, TRAF6, and TAK1/TAB3 to restrain NF-κB and MAPK signaling (PMID:29395066, PMID:31964525, PMID:41062071, PMID:37193092). Independent of catalytic activity, OTUD4 scaffolds USP7 and USP9X to stabilize the DNA alkylation-repair demethylases ALKBH2/3 and the viral activator K-RTA (PMID:25944111, PMID:38215174). OTUD4 additionally localizes to neuronal RNA transport granules and stress granules, binds RNA, and is required for stress granule assembly and cell survival under stress (PMID:31138677).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2015 High

    Establishing that OTUD4 can function independently of its own catalytic activity as a scaffold to recruit USP7 and USP9X answered how alkylation-repair demethylases ALKBH2/3 are stabilized and revealed an unexpected non-enzymatic mode of action for an OTU-family protein.

    Evidence Co-IP, catalytic-dead mutant analysis, and knockdown of OTUD4/USP7/USP9X with alkylating-agent sensitivity readout in human cells

    PMID:25944111

    Open questions at the time
    • Whether the scaffold function extends to other substrates beyond ALKBH2/3
    • Structural basis of OTUD4–USP7/USP9X interaction unknown
  2. 2018 High

    Demonstrating that phosphorylation near the catalytic domain switches OTUD4 from K48 to K63 specificity—dependent on an adjacent UIM—resolved how a single DUB achieves dual-linkage specificity and identified MyD88 as a physiological K63-deubiquitination target that restrains TLR-driven NF-κB activation.

    Evidence In vitro linkage-specificity assays, phospho- and UIM-mutant analysis, Otud4-KO macrophages with TLR stimulation

    PMID:29395066

    Open questions at the time
    • Identity of the kinase(s) responsible for activating phosphorylation
    • Whether phospho-switching is reversible and dynamically regulated in vivo
  3. 2018 High

    Showing that OTUD4 removes K48-linked ubiquitin from MAVS to stabilize it during viral infection established OTUD4 as a positive regulator of antiviral innate immunity, complementing its negative role in TLR/NF-κB signaling.

    Evidence Conditional Otud4-KO mice challenged with VSV, Co-IP, K48-ubiquitination assay, MAVS reconstitution rescue

    PMID:30410068

    Open questions at the time
    • E3 ligase whose K48-ubiquitination of MAVS is countered by OTUD4 not identified
    • Whether OTUD4 acts on other RLR-pathway components
  4. 2019 Medium

    Identifying OTUD4 as an RNA-binding protein that localizes to neuronal RNA transport granules and is required for stress granule assembly expanded its functional repertoire beyond ubiquitin biology into RNA metabolism and stress adaptation.

    Evidence Pulldown/MS from mouse brain, RNA-dependence assay, stress granule imaging, siRNA knockdown with apoptosis readout

    PMID:31138677

    Open questions at the time
    • RNA targets of OTUD4 not identified
    • Whether DUB activity is required for RNA granule function
    • Independent replication in non-neuronal cell types needed
  5. 2020 Medium

    Demonstrating OTUD4-mediated K63-deubiquitination of TRAF6 and enhancement of TGFβ signaling (via TGFβRI retention and SMURF2 inactivation) broadened the set of immune and developmental pathways regulated by OTUD4.

    Evidence Co-IP, K63 ubiquitination assay in hepatic IR model; catalytic-dead mutant and receptor-surface assay for TGFβ axis

    PMID:31964525 PMID:32973272

    Open questions at the time
    • How OTUD4 inactivates SMURF2 mechanistically unclear
    • TGFβ feedback loop not validated in vivo
  6. 2023 Medium

    Identifying OTUD4 as a deubiquitinase for multiple pro-tumorigenic and metabolic substrates—GSDME (pyroptosis), PFKFB3 (glycolysis), SETDB1 (epigenetics/EMT), Snail1 (EMT)—and confirming MyD88 K63-deubiquitination in Paneth cells in vivo consolidated OTUD4 as a versatile regulator of cell fate and inflammation across tissues.

    Evidence Co-IP and ubiquitination assays for each substrate; conditional intestinal KO mice (Paneth-cell-specific) with infection challenge; in vivo tumor and cardiac fibrosis models

    PMID:36411454 PMID:37162556 PMID:37193092 PMID:37739210 PMID:38040050

    Open questions at the time
    • How substrate selectivity is determined among many targets is unknown
    • Whether OTUD4 activity on these substrates is phospho-regulated as for MyD88 is untested
  7. 2024 Medium

    Revealing that OTUD4 cleaves atypical ubiquitin chains (K11, K29, K33 on CDK1; K6, K27 on FGFR1) and stabilizes GPX4 to suppress ferroptosis while also stabilizing CD73 to enable immune evasion extended its chain-type repertoire and linked it to ferroptosis regulation and tumor immunology.

    Evidence Linkage-specific ubiquitination assays, CRISPR-KO ferroptosis sensitivity, TRIM21-counteracting ubiquitination of CD73, in vivo TNBC immune readout, pharmacological inhibitor ST80

    PMID:38429268 PMID:38530357 PMID:40338740

    Open questions at the time
    • How OTUD4 achieves specificity for such diverse chain types is structurally unresolved
    • ST80 inhibitor mechanism and selectivity not fully characterized
  8. 2025 Medium

    Structural and functional dissection of OTUD4's His-loop conferring K63 specificity, identification of a tumor-associated H148Y loss-of-function variant, and expansion of the substrate repertoire to include p53, ZMYND8, MYH9, ISOC2, UBAC1, EGFR, RBM47, and viral SHBs established OTUD4 as a broadly acting deubiquitinase with clinical relevance, and confirmed the scaffold function for USP7 in KSHV reactivation.

    Evidence His-loop mutagenesis and in vitro DUB assay; domain-mapped Co-IPs; Co-IP/deubiquitination assays with rescue experiments; in vivo models (spinal metastasis, xenograft, cardiac IR, colitis); competitive binding assay (SPARC–OTUD4–MyD88)

    PMID:38215174 PMID:38553613 PMID:39888301 PMID:40277358 PMID:41062071 PMID:41107601 PMID:41244113 PMID:41266709 PMID:41297414 PMID:41730840 PMID:41930143

    Open questions at the time
    • No crystal structure of OTUD4 catalytic domain available
    • Relative contribution of catalytic vs. scaffold activities in physiological settings unknown
    • Most substrate studies from single laboratories awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of OTUD4's unusually broad chain-type specificity and phospho-switching mechanism, the identity of kinase(s) regulating the K48-to-K63 switch, how substrate selectivity is achieved among dozens of targets, and whether the scaffold and DUB activities are coordinated or context-exclusive.
  • No crystal or cryo-EM structure of OTUD4
  • Kinase(s) for activating phosphorylation unidentified
  • Systematic substrate-prioritization under physiological conditions not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 18 GO:0140096 catalytic activity, acting on a protein 18 GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 10 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 6 R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 1
Partners
EGFRGPX4MAVSMYD88TAK1TRAF6USP7USP9X

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 OTUD4 acts as a scaffold (in a catalytic-activity-independent manner) to recruit the deubiquitinases USP7 and USP9X, which in turn directly deubiquitinate and stabilize the DNA demethylases ALKBH2 and ALKBH3, thereby promoting resistance to DNA alkylation damage. Co-IP/pulldown, catalytic-dead mutant analysis, loss-of-function (knockdown of OTUD4, USP7, USP9X) with alkylating-agent sensitivity readout The EMBO journal High 25944111
2018 OTUD4 is phosphorylated near its catalytic domain, which converts its nominal K48-linkage specificity into K63-linkage-specific deubiquitinase activity; this phospho-activated K63 activity also requires an adjacent ubiquitin-interacting motif (UIM) that increases affinity for K63-linked chains. The K63 deubiquitinase targets MyD88, thereby negatively regulating TLR-mediated NF-κB activation. In vitro DUB linkage-specificity assay, phospho-mutant analysis, UIM deletion, macrophage KO (Otud4-/- mice) with TLR stimulation and NF-κB readout, mass spectrometry phosphoproteomics Molecular cell High 29395066
2018 Viral infection induces IRF3/7-dependent upregulation of OTUD4, which then interacts with MAVS and removes K48-linked polyubiquitin chains from MAVS, thereby stabilizing MAVS and promoting IRF3/NF-κB-dependent antiviral type I interferon signaling. Co-IP, ubiquitination assay, OTUD4 KO/knockdown (conditional Otud4fl/fl mice and cell lines), VSV infection with IFN/cytokine readout, MAVS reconstitution rescue experiment Cell research High 30410068
2019 OTUD4 is a component of neuronal RNA transport granules under physiological conditions and is recruited to cytoplasmic stress granules upon cellular stress; it interacts with a network of RNA-binding proteins including FMRP, SMN1, G3BP1, and TIA1 in an RNA-dependent manner, and is itself an RNA-binding protein. Knockdown of OTUD4 impairs stress granule formation and leads to apoptotic cell death. Pulldown + mass spectrometry on mouse brain lysates, RNA-dependence assay, live-cell imaging of neuronal RNA granules, stress granule immunofluorescence, siRNA knockdown with apoptosis readout Journal of cell science Medium 31138677
2020 OTUD4 interacts with TRAF6 and removes K63-linked auto-polyubiquitin chains from TRAF6, thereby suppressing NF-κB activation and reducing inflammatory responses in hepatic ischemia-reperfusion injury. Co-IP, ubiquitination assay (K63 linkage), OTUD4 overexpression in hypoxia/reoxygenation model and in vivo hepatic IR model with NF-κB and cytokine readouts Biochemical and biophysical research communications Medium 31964525
2020 OTUD4 enhances TGFβ signalling through both catalytically dependent and independent mechanisms: it promotes membrane retention of TGFβ receptor I and inactivates the TGFβ negative regulator SMURF2; OTUD4 is itself a transcriptional target of TGFβ, forming a positive feedback loop. Catalytic-dead mutant analysis, receptor surface assay, Co-IP, loss-of-function with TGFβ pathway readouts (SMAD phosphorylation) Scientific reports Medium 32973272
2022 OTUD4 directly deubiquitinates GSDME, removing ubiquitin chains and preventing its proteasomal degradation, thereby stabilizing GSDME and enhancing radiation-induced pyroptosis (caspase-3-mediated GSDME cleavage) and radiosensitivity in nasopharyngeal carcinoma. Co-IP, mass spectrometry, ubiquitination assay, in vitro and in vivo functional assays with OTUD4/GSDME modulation, live-cell imaging of pyroptosis Journal of experimental & clinical cancer research Medium 36411454
2023 OTUD4 interacts with and deubiquitinates PFKFB3, a master activator of glycolysis, preventing its degradation and thereby promoting TGFβ1-driven cardiac fibroblast activation and cardiac fibrosis after myocardial infarction. Co-IP, ubiquitination assay, OTUD4 knockdown/overexpression in cardiac fibroblasts, in vivo post-MI mouse model with fibrosis readout Journal of molecular medicine Medium 37162556
2023 In Paneth cells, OTUD4 deubiquitinates MyD88 (removing K63-linked chains), thereby dampening NF-κB and MAPK activation and restricting antimicrobial peptide expression; knockout of OTUD4 leads to hyper-K63-ubiquitination of MyD88, increased AMP production, and resistance to DSS colitis and Salmonella infection. Conditional KO mice (Vil-Cre and Def-Cre Otud4fl/fl), intestinal organoids, ubiquitination assay, LPS/PGN stimulation with NF-κB/MAPK readouts Cell insight High 37193092
2023 IRTKS recruits OTUD4 to SETDB1, where OTUD4 removes K48-linked polyubiquitin chains at K182/K1050 of SETDB1, preventing proteasomal degradation of SETDB1, increasing H3K9me3 at the CDH1 locus, and suppressing E-cadherin expression to drive EMT and tumor metastasis. Co-IP, ubiquitination assay (K48 linkage, specific sites identified), chromatin accessibility assay, E-cadherin transcription readout, in vitro invasion and in vivo metastasis assays Cancer letters Medium 37739210
2023 OTUD4 directly interacts with and deubiquitinates Snail1, preventing its degradation and thereby promoting epithelial-mesenchymal transition and metastasis in triple-negative breast cancer. Co-IP, ubiquitination assay, OTUD4 knockdown with migration/invasion/metastasis readouts, reconstitution of Snail1 in OTUD4-deficient cells Experimental cell research Medium 38040050
2024 OTUD4 directly interacts with CDK1 and removes K11-, K29-, and K33-linked polyubiquitin chains to stabilize CDK1; it also binds FGFR1 and reduces K6- and K27-linked polyubiquitination of FGFR1, thereby indirectly further stabilizing CDK1 and activating the downstream MAPK signaling pathway in glioblastoma. Co-IP, ubiquitination assay (linkage-specific), OTUD4 knockdown/overexpression with proliferation/invasion readouts, in vivo xenograft Cell death & disease Medium 38429268
2024 OTUD4 deubiquitinates and stabilizes CD73, counteracting TRIM21-mediated ubiquitination of CD73, within a TGF-β-orchestrated signaling axis; this OTUD4/CD73 proteolytic axis suppresses antitumor immune responses in triple-negative breast cancer. Multiomic analysis, Co-IP, ubiquitination assay (TRIM21 as E3 ligase), pharmacological inhibitor (ST80) disrupting OTUD4-CD73 interaction, in vivo TNBC models with immune readout The Journal of clinical investigation Medium 38530357
2024 OTUD4 acts as a non-catalytic adaptor to recruit USP7 to the KSHV replication and transcription activator (K-RTA), facilitating K-RTA deubiquitination by USP7 and thereby stabilizing K-RTA to promote KSHV lytic reactivation. Co-IP, ubiquitination assay, OTUD4 catalytic-dead mutant (showing DUB activity dispensable), USP7 recruitment assay, viral reactivation readout PLoS pathogens Medium 38215174
2024 OTUD4 directly interacts with and deubiquitinates RBM47, preventing its proteasomal degradation; stabilized RBM47 promotes ATF3 mRNA stability and ATF3-mediated ferroptosis, suppressing ccRCC progression. Co-IP, ubiquitination assay, OTUD4 overexpression/knockdown, RBM47 interference rescue experiment, ferroptosis assay Apoptosis Medium 38553613
2025 OTUD4 interacts with core components of the TAK1 signalosome (TAK1, TAB1, TAB3) and removes K63-linked polyubiquitin chains from TAK1 and TAB3, suppressing TNF-induced NF-κB activation. A histidine-centered loop (His loop) in the catalytic domain confers K63-linkage specificity; a tumor-associated H148Y variant in this loop retains TAK1 binding but abolishes DUB activity, leading to sustained NF-κB activation. Co-IP, in vitro K63-specific DUB assay, His-loop mutant and H148Y variant analysis, TNF stimulation with NF-κB readout The Journal of biological chemistry Medium 41062071
2025 OTUD4 directly deubiquitinates GPX4, removing ubiquitin chains to prevent its proteasomal degradation; OTUD4 also impedes RHEB-mediated autophagic degradation of GPX4, collectively suppressing ferroptosis and promoting tumor cell survival. CRISPR-Cas9 KO cell lines, ferroptosis inducer sensitivity assay, Co-IP, ubiquitination assay, RHEB-autophagy axis analysis, in vivo tumor models Cell reports Medium 40338740
2025 OTUD4 interacts with UBAC1 and maintains UBAC1 protein stability through deubiquitination; OTUD4 deficiency decreases UBAC1 expression, thereby impairing autophagic flux in cardiomyocytes and modulating myocardial ischemia-reperfusion injury. Co-IP, ubiquitination assay, OTUD4 knockdown/overexpression in OGD-R cell model and LAD-ligation MIRI mouse model, autophagic flux markers (LC3, p62, LAMP2), AKT/mTOR pathway readout Journal of molecular medicine Medium 41107601
2025 SPARC competitively binds OTUD4 in conjunction with MyD88, disrupting OTUD4's deubiquitinase regulation of MyD88 and facilitating p65 nuclear translocation, thereby activating the p65-MLCK/MLC2 pathway and compromising intestinal barrier integrity in Crohn's disease. Co-IP, competitive binding assay, p65 nuclear translocation imaging, SPARC KO mouse colitis model, barrier permeability readouts Advanced science Medium 39888301
2025 OTUD4 directly interacts with and deubiquitinates p53, stabilizing it and enhancing its transcriptional activity to suppress colorectal cancer progression; p53 knockdown abrogates OTUD4-mediated tumor suppression. Co-IP, ubiquitination assay, OTUD4 knockdown/overexpression, p53 knockdown rescue experiment, proliferation/migration/invasion readouts Discover oncology Medium 41266709
2025 TRIM21 promotes K48-linked ubiquitination of the small hepatitis B surface antigen (SHBs) at K122 leading to proteasomal degradation, while OTUD4 counteracts TRIM21-induced ubiquitination to stabilize SHBs; OTUD4 interacts with SHBs via its N-terminal 1–180 amino acids. Co-IP, GST pulldown (in vitro), K48-ubiquitination assay (site-directed at K122), TRIM21/OTUD4 overexpression with SHBs stability readout Journal of virology Medium 40277358
2025 OTUD4 directly deubiquitinates and stabilizes ZMYND8, promoting assembly of the DDX3X-CK1ε complex that activates WNT/β-catenin signaling, upregulates CSF1, and drives M2 macrophage polarization to foster an immunosuppressive niche in TNBC spinal metastasis. Co-IP, ubiquitination assay, OTUD4 KO/overexpression, in vivo spinal metastasis model, macrophage co-culture readouts Neoplasia Medium 41297414
2025 WSB1 promotes interaction between ISOC2 and OTUD4, leading to OTUD4-mediated deubiquitination and stabilization of ISOC2, which suppresses P16INK4a expression and drives prostate cancer progression. Mass spectrometry, Co-IP, ubiquitination assay, WSB1/ISOC2/OTUD4 knockdown with proliferation/migration readouts, in vivo xenograft American journal of cancer research Medium 41244113
2025 OTUD4 directly deubiquitinates MYH9, preventing its proteasomal degradation, thereby stabilizing MYH9 which suppresses prostate cancer progression through interactions with cell adhesion molecules. Co-IP, mass spectrometry, ubiquitination assay, OTUD4 KO/overexpression, in vivo xenograft Oncology research Medium 41930143
2026 OTUD4 stabilizes EGFR by directly interacting with it (via OTUD4 aa 568–1114 and EGFR aa 958–1210) and cleaving K48-linked polyubiquitin chains; OTUD4 is additionally recruited by NRP1 to further deubiquitinate and stabilize EGFR, activating the PI3K/AKT pathway in TNBC. Co-IP (domain-mapping), ubiquitination assay (K48 linkage), OTUD4 knockdown, NRP1 co-recruitment assay, PI3K/AKT pathway readout Cell death & disease Medium 41730840

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Induction of OTUD4 by viral infection promotes antiviral responses through deubiquitinating and stabilizing MAVS. Cell research 95 30410068
2018 OTUD4 Is a Phospho-Activated K63 Deubiquitinase that Regulates MyD88-Dependent Signaling. Molecular cell 93 29395066
2015 Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase. The EMBO journal 85 25944111
2022 OTUD4-mediated GSDME deubiquitination enhances radiosensitivity in nasopharyngeal carcinoma by inducing pyroptosis. Journal of experimental & clinical cancer research : CR 69 36411454
2024 OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway. Cell death & disease 31 38429268
2024 Pharmacological suppression of the OTUD4/CD73 proteolytic axis revives antitumor immunity against immune-suppressive breast cancers. The Journal of clinical investigation 27 38530357
2019 New roles for the de-ubiquitylating enzyme OTUD4 in an RNA-protein network and RNA granules. Journal of cell science 26 31138677
2020 OTUD4 alleviates hepatic ischemia-reperfusion injury by suppressing the K63-linked ubiquitination of TRAF6. Biochemical and biophysical research communications 22 31964525
2023 Upregulation of glycolytic enzyme PFKFB3 by deubiquitinase OTUD4 promotes cardiac fibrosis post myocardial infarction. Journal of molecular medicine (Berlin, Germany) 19 37162556
2013 Zebrafish transforming growth factor-β-stimulated clone 22 domain 3 (TSC22D3) plays critical roles in Bmp-dependent dorsoventral patterning via two deubiquitylating enzymes Usp15 and Otud4. Biochimica et biophysica acta 16 23665588
2023 Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes. Acta neuropathologica 14 37149835
2023 The deubiquitinase OTUD4 inhibits the expression of antimicrobial peptides in Paneth cells to support intestinal inflammation and bacterial infection. Cell insight 14 37193092
2023 Cooperation between IRTKS and deubiquitinase OTUD4 enhances the SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression. Cancer letters 12 37739210
2020 OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex. Scientific reports 12 32973272
2024 Deubiquitinating enzyme OTUD4 stabilizes RBM47 to induce ATF3 transcription: a novel mechanism underlying the restrained malignant properties of ccRCC cells. Apoptosis : an international journal on programmed cell death 11 38553613
2025 OTUD4 inhibits ferroptosis by stabilizing GPX4 and suppressing autophagic degradation to promote tumor progression. Cell reports 10 40338740
2023 Deubiquitinating enzyme OTUD4 regulates metastasis in triple-negative breast cancer by stabilizing Snail1. Experimental cell research 10 38040050
2025 Elevated SPARC Disrupts the Intestinal Barrier Integrity in Crohn's Disease by Interacting with OTUD4 and Activating the MYD88/NF-κB Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39888301
2024 Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases. PLoS pathogens 8 38215174
2023 CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation. Cell death & disease 8 37726265
2025 OTUD4-mediated inhibition of YAP1 signaling pathway in ovarian cancer: Implications for macrophage polarization and recruitment. International immunopharmacology 3 39778277
2025 Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy. PLoS pathogens 3 40208866
2025 Ubiquitin-dependent proteasomal degradation of small hepatitis B virus surface antigen mediated by TRIM21 and antagonized by OTUD4. Journal of virology 2 40277358
2025 The deubiquitinase OTUD4 suppresses TAK1 kinase-dependent NF-κB signaling and inflammation. The Journal of biological chemistry 1 41062071
2024 NRF2 regulates EGF stability through OTUD4 in lung adenocarcinoma. Biochemical and biophysical research communications 1 38518721
2026 Fenofibrate potentiates the therapeutic efficacy of EZH2 inhibitors on melanoma via TRIM21- and OTUD4-mediated EZH2 ubiquitination. British journal of pharmacology 0 41652905
2026 OTUD4 regulates pancreatic cancer progression via Hippo/YAP axis. Neoplasia (New York, N.Y.) 0 41687501
2026 OTUD4 deubiquitination stabilizes EGFR and activates the PI3K/AKT pathway to promote the invasiveness of triple-negative breast cancer. Cell death & disease 0 41730840
2026 The ovarian tumor domain-containing protein 4 (OTUD4)-targeted ferroptosis inhibitor Maclekarpine E attenuates ulcerative colitis. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41759427
2026 OTUD4 Inhibits Prostate Cancer by Deubiquitinating MYH9. Oncology research 0 41930143
2025 Deubiquitinase OTUD4 Stabilizes SLC5A2 to Promote Pancreatic Cancer Proliferation and Migration Through Enchaining Glycolysis-Mediated Autophagy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40719816
2025 Suppression of OTUD4 protects against myocardial ischemia-reperfusion injury by increasing autophagic flux and inhibiting apoptosis in cardiomyocytes. Journal of molecular medicine (Berlin, Germany) 0 41107601
2025 WSB1 promotes prostate cancer malignancy through OTUD4-mediated ISOC2 stabilization and P16INK4a suppression. American journal of cancer research 0 41244113
2025 OTUD4 suppresses colorectal cancer progression through deubiquitinating p53. Discover oncology 0 41266709
2025 OTUD4-ZMYND8-DDX3X Axis Drives Immunosuppressive Microenvironment in Spinal Metastases of Triple-Negative Breast Cancer. Neoplasia (New York, N.Y.) 0 41297414