Affinage

OTUD1

OTU domain-containing protein 1 · UniProt Q5VV17

Length
481 aa
Mass
51.1 kDa
Annotated
2026-04-29
60 papers in source corpus 39 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTUD1 is an OTU-family deubiquitinase that functions as a broad-specificity regulator of ubiquitin-dependent signaling, cleaving K63-, K48-, K33-, and K6-linked polyubiquitin chains from diverse substrates to control inflammation, innate immunity, cell death, antioxidant defense, and protein trafficking. Its catalytic OTU domain (active-site C320) preferentially hydrolyzes K63-linked chains—enhanced by a C-terminal UIM—to modulate NF-κB signaling (via RIPK1, RIP2, CARD9, CDK9), antiviral IFN responses (via IRF3, Smurf1/MAVS), Hippo-independent YAP activity, β-catenin nuclear translocation, COPII-mediated ER-to-Golgi transport (via SEC23B), ribosome quality control (via ZNF598/RPS10), and AMPK activation, while K48-chain cleavage stabilizes substrates including PTEN, NRF2, p53, PRDX1, and C/EBPβ (PMID:29891922, PMID:34876703, PMID:32075857, PMID:29734366, PMID:37639212, PMID:36445135, PMID:40300668, PMID:39079388, PMID:40683882, PMID:35280681). Beyond its catalytic function, OTUD1 possesses an N-terminal intrinsically disordered region containing an ETGE motif that binds KEAP1 to regulate the NRF2 antioxidant response, and a short peptide (OUN-36) that directly inhibits Akt membrane recruitment independently of deubiquitinase activity (PMID:35941131, PMID:36640312). OTUD1 loss-of-function exacerbates inflammatory bowel disease, cardiac hypertrophy, sepsis, and fungal susceptibility in mouse models, while a UC-associated G430V mutation abolishes RIPK1 deubiquitination, linking OTUD1 dysfunction to human inflammatory disease (PMID:34876703, PMID:37153745, PMID:33789983).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2017 High

    Establishing OTUD1 as a deubiquitinase that suppresses TGF-β-driven metastasis revealed its first defined substrate (SMAD7) and demonstrated it cleaves an atypical K33 linkage at a specific lysine, coupling deubiquitination to E3-ligase recruitment and receptor turnover.

    Evidence Loss-of-function screen in mice, in vitro DUB assay with K33-linkage specificity, SMAD7 K220 mutagenesis, orthotopic transplantation

    PMID:29235476

    Open questions at the time
    • Whether K33-linked ubiquitination of SMAD7 is catalyzed by a specific E3 ligase was not identified
    • Structural basis for K33 selectivity unresolved
  2. 2018 High

    Two contemporaneous studies established OTUD1 as a negative regulator of innate antiviral immunity through two distinct mechanisms—stabilizing Smurf1 to degrade MAVS/TRAF3/TRAF6, and removing K63-linked ubiquitin from IRF3 K98 to block its nuclear function—revealing OTUD1 as a multi-substrate feedback inhibitor in the IFN pathway.

    Evidence OTUD1 KO mice with viral challenge for Smurf1 axis; Co-IP and ubiquitination assays with patient mutation validation for IRF3 axis

    PMID:29734366 PMID:30100102

    Open questions at the time
    • Whether Smurf1 stabilization and IRF3 deubiquitination operate in the same cell type simultaneously
    • Relative contribution of each axis to net IFN output in vivo
  3. 2018 High

    Identification of YAP as a K63-deubiquitination target showed OTUD1 opposes SCF-SKP2-mediated non-proteolytic ubiquitination to control YAP nuclear localization independently of canonical Hippo kinase signaling, broadening OTUD1's role beyond immune regulation.

    Evidence DUB library screen, K321/K497 mutagenesis, localization assays

    PMID:29891922

    Open questions at the time
    • Physiological contexts where OTUD1-YAP axis dominates over Hippo pathway unclear
    • No in vivo phenotype shown for this axis
  4. 2020 High

    Demonstrating that OTUD1 cleaves a K6-linked ubiquitin chain from IRF3 that specifically controls DNA-binding capacity—without affecting stability, dimerization, or nuclear entry—revealed an unprecedented non-degradative, non-K63 regulatory mechanism for transcription factor activity.

    Evidence Linkage-specific assay, ChIP showing IRF3 dissociation from promoters, Otud1−/− mice with viral/LPS challenge

    PMID:32075857

    Open questions at the time
    • The E3 ligase installing K6-linked ubiquitin on IRF3 was not identified
    • Whether K6 and K63 modifications on IRF3 K98 are mutually exclusive or sequential
  5. 2021 High

    Multiple 2021 studies expanded OTUD1's substrate repertoire to ferroptosis (IREB2), NF-κB (RIPK1), antifungal immunity (CARD9), and apoptosis (AIF, MCL1), establishing it as a pleiotropic deubiquitinase whose net cellular outcome depends on cell type and stimulus context.

    Evidence RIPK1 K63-deubiquitination with UC patient G430V variant in DSS colitis KO mice; IREB2 stabilization with ferroptosis/immune readouts; CARD9 deubiquitination with fungal KO mouse model; AIF site-specific mutagenesis (K244/K255) and MCL1 degradation via DCAF10-CUL4A complex

    PMID:33393230 PMID:33789983 PMID:33898171 PMID:34876703

    Open questions at the time
    • How substrate selectivity is achieved among many competing targets in the same cell
    • Whether the G430V UC mutation affects substrates beyond RIPK1
  6. 2022 High

    Discovery that OTUD1 possesses deubiquitinase-independent functions—an N-terminal OUN-36 peptide blocking Akt PH-domain membrane recruitment, and an ETGE motif engaging KEAP1—revealed that OTUD1's disordered N-terminus operates as an autonomous signaling module.

    Evidence PH domain binding assay and Akt phosphorylation studies for OUN-36; DUB screen, MS interactome, ETGE domain deletion with KO mouse inflammatory models for KEAP1 binding

    PMID:35941131 PMID:36640312

    Open questions at the time
    • Structural basis of OUN-36/PH domain interaction not solved
    • Whether ETGE-KEAP1 and catalytic functions are coordinated or independent in vivo
  7. 2022 Medium

    Identification of OTUD1 as an antagonist of ZNF598-mediated ribosome ubiquitination during translational stalling linked this deubiquitinase to ribosome quality control, a function distinct from its signaling roles.

    Evidence BioID proximity labeling, polysome profiling, RPS10 ubiquitination assay, rare-codon mRNA stability analysis

    PMID:36445135

    Open questions at the time
    • Whether OTUD1 acts on stalled ribosomes in vivo under physiological stress
    • No structural or reconstituted in vitro ribosome-OTUD1 complex
    • Independent replication needed
  8. 2023 High

    Studies in 2023 established OTUD1 as a regulator of cardiac pathophysiology through STAT3 K63-deubiquitination (promoting inflammatory cardiac remodeling), SEC23B K63-deubiquitination (restricting COPII secretory transport), NRF2 stabilization (protecting against oxidative injury), and CARD9 K33-deubiquitination (promoting CBM complex assembly in macrophages), revealing tissue-specific and linkage-specific substrate programs.

    Evidence LC-MS/MS with Co-IP and C320 mutagenesis for STAT3 in KO mice; K81 site-specific assay and neutrophil KO for SEC23B; ETGE peptide treatment and KO mouse I/R model for NRF2; myeloid-specific KO and CBM reconstitution for CARD9

    PMID:37153745 PMID:37639212 PMID:39079388 PMID:39118286

    Open questions at the time
    • How OTUD1 is directed to K33 vs K63 chains on different substrates in the same cell type
    • Whether SEC23B regulation is specific to neutrophils or generalizable
  9. 2023 High

    Development of UbVOD.1, a ubiquitin variant inhibitor bridging the OTU domain and UIM, provided the first tool-grade inhibitor of OTUD1 and confirmed that the UIM contributes to catalytic engagement with ubiquitin chains.

    Evidence Phage display selection, in vitro IC50 quantification, cellular RIPK1 ubiquitination rescue with di-UbV

    PMID:37589489

    Open questions at the time
    • No in vivo application of UbVOD.1 demonstrated
    • Selectivity across the full OTU DUB family not comprehensively tested
  10. 2024 High

    OTUD1 was shown to regulate cardiac calcium handling by stabilizing PDE5A through K48-deubiquitination, inactivating the cGMP-PKG-SERCA2a axis, and to impair AMPK activation by deubiquitinating AMPKα2 at K60/K379 and blocking CAMKK2 binding, establishing OTUD1 as a driver of heart failure and diabetic cardiomyopathy.

    Evidence LC-MS/MS, C320 mutagenesis, domain mapping for PDE5A in ISO/MI KO mice; AMPKα2 K60/K379 mutagenesis, cardiomyocyte-specific KO in T1DM/T2DM models with scRNA-seq

    PMID:38185350 PMID:40683882

    Open questions at the time
    • Whether PDE5A and AMPKα2 deubiquitination interact in the same cardiac pathology
    • Therapeutic targeting of OTUD1 in heart failure not yet demonstrated
  11. 2025 High

    Recent work further expanded OTUD1 substrates to β-catenin (controlling angiogenesis in diabetic wound healing), C/EBPβ (driving Alzheimer's neuroinflammation), PRDX1 (suppressing osteoclastogenesis), HK2 (promoting NLRP3-driven pyroptosis), and p53 (promoting endothelial procoagulant programs), demonstrating context-dependent pro- or anti-inflammatory outcomes.

    Evidence IP-MS with site-specific mutagenesis (β-catenin K496/K508/K625, C/EBPβ K253), myeloid-specific KO with micro-CT for PRDX1, OTUD1 KO in CLP sepsis model for HK2, L357 mutagenesis with thrombosis model for p53

    PMID:40300668 PMID:40335710 PMID:40500776 PMID:40585986 PMID:41967174

    Open questions at the time
    • How OTUD1 substrate selection is regulated post-translationally in different tissues
    • No unifying structural model of OTUD1 engaged with different chain types
    • Contribution of disordered N-terminus to substrate recruitment largely unmapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how OTUD1 achieves substrate selectivity among its many targets in a given cell, whether its catalytic and non-catalytic (ETGE, OUN-36) functions are coordinately regulated, and whether a full-length structural model can explain its multi-linkage specificity.
  • No full-length crystal or cryo-EM structure
  • No systematic selectivity profiling across chain types with endogenous substrates
  • Upstream signals governing OTUD1 protein turnover and activity remain fragmentary

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 27 GO:0140096 catalytic activity, acting on a protein 16 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 12 R-HSA-162582 Signal Transduction 10 R-HSA-392499 Metabolism of proteins 7 R-HSA-1643685 Disease 6 R-HSA-5357801 Programmed Cell Death 5 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-8953854 Metabolism of RNA 1 R-HSA-9609507 Protein localization 1
Partners
CARD9IRF3KEAP1PDE5APRKAA2RIPK1SMAD7STAT3

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 OTUD1 is a deubiquitinase that removes K63-linked polyubiquitin chains from YAP, reversing SCFSKP2-mediated non-proteolytic K63-linked ubiquitination at K321 and K497. This ubiquitination promotes YAP interaction with TEAD, nuclear localization, and transcriptional activity independently of Hippo signaling; OTUD1 overexpression retains YAP in the cytoplasm and inhibits its activity. DUB library screen, co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis, overexpression/knockdown with localization readouts Nature communications High 29891922 31225491
2017 OTUD1 directly deubiquitinates SMAD7, cleaving K33-linked polyubiquitin chains at SMAD7 K220, which prevents SMAD7 proteasomal degradation and exposes the SMAD7 PY motif for SMURF2 binding, leading to TβRI turnover at the cell surface and suppression of TGF-β pro-metastatic signaling. Loss-of-function screen in mice, co-immunoprecipitation, in vitro deubiquitination assay, ubiquitin linkage-specific analysis, site-directed mutagenesis, xenograft and orthotopic transplantation models Nature communications High 29235476
2021 OTUD1 deubiquitinates and stabilizes IREB2 (iron-responsive element-binding protein 2), which in turn promotes TFRC-mediated iron transport, increases ROS generation, and induces ferroptosis; OTUD1 loss reduces iron import and dampens tumor-reactive T-cell accumulation. Co-immunoprecipitation, ubiquitination assay, genetic knockdown/knockout with ferroptosis and immune cell readouts EMBO reports High 33393230
2021 OTUD1 physically interacts with RIPK1 and selectively cleaves K63-linked polyubiquitin chains from RIPK1, thereby inhibiting recruitment of NEMO and suppressing NF-κB activation; a UC-associated OTUD1 G430V mutation abolishes this activity. Co-immunoprecipitation, ubiquitin linkage-specific assay, knockout mouse model (DSS colitis), bone marrow transplantation, patient mutation functional analysis Cellular & molecular immunology High 34876703
2018 RNA virus infection induces OTUD1 expression via NF-κB-dependent mechanisms; OTUD1 then deubiquitinates and stabilizes the E3 ligase Smurf1, which promotes ubiquitination-dependent degradation of MAVS, TRAF3, and TRAF6, thereby inhibiting type I IFN production as a negative feedback loop. Co-immunoprecipitation, ubiquitination assay, OTUD1-deficient mice with viral infection challenge, overexpression/knockdown PLoS pathogens High 29734366
2020 OTUD1 deubiquitinates IRF3 by cleaving K6-linked polyubiquitin chains at IRF3 K98; K6-linked ubiquitination is required for IRF3 DNA-binding capacity at IFN gene promoters without affecting IRF3 stability, dimerization, or nuclear translocation. OTUD1 removal of this modification dissociates IRF3 from target gene promoters. Co-immunoprecipitation, linkage-specific ubiquitination assay, chromatin immunoprecipitation, Otud1-/- cells and mice with viral/LPS challenge Journal of immunology High 32075857
2018 OTUD1 directly interacts with IRF3 and removes K63-linked polyubiquitin chains at IRF3 K98, inhibiting IRF3 nuclear translocation and transcriptional activity; loss-of-function OTUD1 mutations found in autoimmune patients impair this deubiquitinase activity or IRF3 association. FOXO3 signaling is required for OTUD1 induction upon antigenic stimulation. Co-immunoprecipitation, ubiquitination assay, patient mutation functional analysis, OTUD1-deficient cellular models Journal of autoimmunity High 30100102
2022 OTUD1 suppresses canonical NF-κB activation by hydrolyzing K63-linked ubiquitin chains from NF-κB signaling factors including LUBAC substrates. OTUD1 also binds KEAP1 through an ETGE motif in its N-terminal intrinsically disordered region, regulating the antioxidant response and ROS-induced cell death (oxeiptosis). In Otud1-/- mice, inflammation and oxidative damage are enhanced in IBD, acute hepatitis, and sepsis models. DUB screen (88 human DUBs), mass spectrometry interactome, ubiquitination assay, Otud1-/- mouse models, domain deletion analysis Cell death & disease High 35941131
2021 OTUD1 deubiquitinates AIF at K244 (disrupting mitochondrial structure and oxidative phosphorylation) and at K255 (enhancing AIF DNA-binding ability to promote caspase-independent parthanatos). OTUD1 also stabilizes DCAF10 and recruits the CUL4A-DDB1 complex to promote MCL1 degradation, activating caspase-dependent apoptosis. Co-immunoprecipitation, site-directed mutagenesis at AIF K244 and K255, ubiquitination assays, functional apoptosis readouts Advanced science High 33898171
2021 OTUD1 directly interacts with CARD9 and cleaves polyubiquitin chains from CARD9, which is required for CARD9-mediated NF-κB and MAPK activation in antifungal innate immunity; OTUD1-deficient mice are more susceptible to fungal infection. Co-immunoprecipitation, ubiquitination assay, Otud1-/- mouse fungal infection model Journal of immunology High 33789983
2023 OTUD1 binds the SH2 domain of STAT3 and deubiquitinates STAT3 K63-linked chains via its catalytic C320 residue, promoting STAT3 phosphorylation and nuclear translocation, thereby inducing inflammatory, fibrotic, and hypertrophic responses in cardiomyocytes; OTUD1 KO mice are protected from angiotensin II- and TAC-induced cardiac remodeling. LC-MS/MS combined with Co-IP, site-directed mutagenesis (C320), AAV9 overexpression, OTUD1 KO mouse models Theranostics High 37153745
2022 OTUD1's N-terminal intrinsically disordered region contains a short peptide (OUN-36) that binds the Akt PH domain at residues required for PtdIns(3,4,5)P3 recognition, inhibiting Akt membrane localization and phosphorylation independently of OTUD1 deubiquitinase activity. Co-immunoprecipitation, domain deletion analysis, peptide binding assay, cell membrane localization studies, Akt phosphorylation assays Cell reports High 36640312
2023 OTUD1 interacts with CARD9 and removes K33-linked ubiquitin from CARD9, promoting assembly of the CARD9-BCL10-MALT1 (CBM) complex and NF-κB activation in macrophages during isoproterenol-induced cardiac inflammation; myeloid-specific OTUD1 deletion attenuates cardiac remodeling. Co-immunoprecipitation, linkage-specific ubiquitination assay, Card9-/- and Otud1-/- bone marrow reconstitution, primary macrophage mechanistic studies Clinical and translational medicine High 39118286
2024 OTUD1 binds directly to GAF1 and PDEase domains of PDE5A and reverses K48-linked ubiquitination of PDE5A via its C320 catalytic residue, preventing proteasomal degradation of PDE5A, which inactivates the cGMP-PKG-SERCA2a signaling axis and dysregulates calcium handling in cardiomyocytes, promoting heart failure. LC-MS/MS combined with Co-IP, site-directed mutagenesis (C320), OTUD1 KO mouse (ISO and MI models), domain binding mapping Biochimica et biophysica acta. Molecular basis of disease High 38185350
2023 OTUD1 interacts with Notch2-ICD (NICD) and cleaves ubiquitin at NICD K1770, leading to NICD protein accumulation in T cells, which promotes Th1/Th17 differentiation and amplifies graft-versus-host disease; dapagliflozin was identified as an inhibitor of the OTUD1/NICD axis. Co-immunoprecipitation, site-specific ubiquitination assay (K1770), FDA-approved drug screen, aGVHD mouse model Blood High 36574342
2022 OTUD1 interacts with and deubiquitinates PTEN, stabilizing PTEN protein levels to suppress PI3K/AKT and TNF-α/NF-κB signaling in renal cancer cells. Co-immunoprecipitation, ubiquitination assay, RNA-seq pathway analysis, knockdown/overexpression International journal of biological sciences Medium 35280681
2021 OTUD1 interacts with MCL1 and promotes its deubiquitination in an enzymatic-activity-dependent manner, stabilizing MCL1 protein and antagonizing BH3-mimetic inhibitor-induced cell death. DUB library screen, co-immunoprecipitation, ubiquitination assay, cell viability assay Cancer cell international Medium 31467488
2021 OTUD1 deubiquitinates and stabilizes Bim at lysine 3, preventing its proteasomal degradation; melatonin-induced Sp1 activation drives OTUD1 transcription, leading to Bim stabilization and apoptosis in cancer cells. Co-immunoprecipitation, site-directed mutagenesis (Bim K3), ubiquitination assay, siRNA knockdown, xenograft model Journal of pineal research Medium 34826170
2022 OTUD1 catalytic activity resolves ribosome stalling on polyA sequences by inhibiting ZNF598-mediated RPS10 ubiquitination, and promotes polysome formation; OTUD1 also associates with ribosome subunits and elongation factors and regulates stability of rare-codon-rich mRNAs by antagonizing ZNF598. Proximity labeling-based interactome (BioID), co-immunoprecipitation with ribosome subunits, polysome profiling, ubiquitination assay for RPS10, gene expression analysis Molecular and cellular biology Medium 36445135
2023 OTUD1 cleaves K63-linked polyubiquitin chains from SEC23B at K81, negatively regulating the COPII secretory machinery and limiting ER-to-Golgi protein trafficking, thereby restricting surface expression of CD9 and CD47 and suppressing secretory neutrophil polarization. Co-immunoprecipitation, linkage-specific ubiquitination assay (K81), neutrophil-specific OTUD1 depletion, Brefeldin A rescue experiment Advanced science High 37639212
2023 OTUD1 deubiquitinates and stabilizes NRF2 through its C320 catalytic residue and ETGE motif, attenuating hepatic ischemia/reperfusion-induced oxidative stress; an ETGE-containing peptide mimics this protective effect in vivo. Co-immunoprecipitation, deubiquitination assay, site-directed mutagenesis (C320), OTUD1 KO mouse (I/R model), ETGE peptide in vivo treatment Redox biology High 39079388
2023 OTUD1 interacts with RIP2 and cleaves K63-linked polyubiquitin chains from RIP2, inhibiting NF-κB activation; OTUD1 deficiency exacerbates cerebral ischemic injury by allowing excess RIP2 ubiquitination and NF-κB-driven inflammation. Co-immunoprecipitation, confocal microscopy co-localization, immunofluorescence, dual-luciferase NF-κB assay, OTUD1-/- mouse (MCAO model) Journal of neuroinflammation High 38012669
2023 OTUD1 deubiquitinates CDK9 via K63-linkage at its C320 catalytic residue, promoting CDK9 phosphorylation and activation to induce inflammatory responses and fibrosis in kidney epithelial cells; OTUD1 KO mice are protected from angiotensin II-induced hypertensive renal disease. Co-immunoprecipitation, site-directed mutagenesis (C320), OTUD1 KO mouse (Ang II model), CDK9 inhibitor rescue Acta pharmacologica Sinica High 38110583
2024 OTUD1 directly binds AMPKα2, deubiquitinates it at K60/K379, and inhibits AMPKT172 phosphorylation by impeding the AMPKα2-CAMKK2 interaction, resulting in mitochondrial dysfunction in cardiomyocytes and diabetic cardiomyopathy; cardiomyocyte-specific OTUD1 KO restores AMPK activity. Co-immunoprecipitation, site-directed mutagenesis (K60/K379), cardiomyocyte-specific KO mouse (T1DM and T2DM models), single-cell RNA-seq, CAMKK2 interaction assay Nature communications High 40683882
2025 OTUD1 promotes HK2 dissociation from mitochondria via selective K63-linked deubiquitination of HK2, activating the NLRP3 inflammasome and triggering microglia pyroptosis, leading to neuroinflammation and cognitive deficits in sepsis-associated encephalopathy. Co-immunoprecipitation, molecular docking, 3D confocal microscopy, K63-specific ubiquitination assay, OTUD1 KO mouse (CLP model), single-cell RNA-seq Journal of neuroinflammation High 40500776
2024 OTUD1 deubiquitinates and stabilizes PGAM5 by reversing its ubiquitination, leading to robust activation of the ASK1-p38/JNK signaling pathway to accelerate cardiac hypertrophy; m6A modification by METTL3 of OTUD1 mRNA promotes its stability and elevated expression. RNA immunoprecipitation (RIP) for m6A, IP-MS for substrate identification, domain deletion constructs, cardiac-specific KO mice (TAC model), ASK1 knockdown rescue International journal of biological sciences High 39309432
2023 OTUD1 contains an N-terminal ETGE motif within an alanine/proline/glycine-rich intrinsically disordered region that mediates binding to KEAP1, placing OTUD1 in the KEAP1-NRF2 antioxidant axis; the OTU catalytic domain preferentially hydrolyzes K63-linked ubiquitin chains, with the UIM enhancing this preference. Domain analysis, in vitro ubiquitin chain hydrolysis assay, KEAP1 binding assay, UIM deletion analysis Antioxidants Medium 36829909
2023 An ubiquitin variant inhibitor (UbVOD.1) was developed that binds OTUD1 with nanomolar affinity bridging the catalytic OTU domain and UIM, inhibiting OTUD1 activity toward mono-Ub, K63-linked di-Ub, and poly-Ub chains of other linkages in vitro, and inhibiting OTUD1-mediated deubiquitination of RIPK1 in cells as a di-UbV. Phage display UbV library selection, in vitro deubiquitination IC50 assay, in vivo di-UbV expression with RIPK1 ubiquitination readout The Biochemical journal High 37589489
2022 OTUD1 deubiquitinates and stabilizes KLF4 in non-small cell lung cancer cells, with OTUD1 overexpression inhibiting NSCLC cell progression and KLF4 knockdown reversing this effect. Co-immunoprecipitation, cycloheximide chase, deubiquitination assay, siRNA knockdown rescue Thoracic cancer Medium 35098684
2023 OTUD1 deubiquitinates and stabilizes FHL1 in lung adenocarcinoma cells, inhibiting tumor proliferation and migration in vitro and in vivo. IP-MS, co-immunoprecipitation, ubiquitination assay, xenograft and urethane-induced lung cancer models Cellular oncology Medium 36929488
2025 OTUD1 interacts with BST-2, reducing its K48- and K63-linked ubiquitination and increasing BST-2 protein stability, thereby inhibiting HIV-1 particle release. siRNA DUB screen, co-immunoprecipitation, ubiquitin linkage-specific assay, HIV-1 release assay Viruses Medium 40007014
2025 OTUD1 directly binds C/EBPβ and removes K48-linked ubiquitin chains at C/EBPβ K253, stabilizing C/EBPβ and activating C/EBPβ-NF-κB-mediated inflammatory responses in microglia, promoting Alzheimer's disease pathology. LC-MS/MS combined with Co-IP, site-directed mutagenesis (K253), OTUD1 knockdown in microglia, AD mouse model cognitive readout Acta pharmacologica Sinica High 40335710
2025 OTUD1 deubiquitinates TIPE2, and this interaction suppresses TAK1-mediated MAPK and NF-κB signaling to protect against sepsis-induced lung injury. Co-immunoprecipitation, immunofluorescence co-localization, western blotting for deubiquitination, in vivo sepsis model Biochemical pharmacology Medium 38996928
2025 OTUD1 directly interacts with β-catenin and reduces K63-linked ubiquitination at β-catenin K496, K508, and K625 via its C320 catalytic residue, facilitating β-catenin phosphorylation and restricting its nuclear translocation, thereby downregulating angiogenesis-related factors and impairing wound healing in diabetic mice. IP-MS, co-immunoprecipitation, site-directed mutagenesis (C320 and K496/K508/K625), endothelial-specific AAV knockdown, diabetic mouse wound healing model Journal of advanced research High 40300668
2025 OTUD1 deubiquitinates PRDX1 by reversing K48-linked ubiquitination, maintaining PRDX1 stability, mitigating mitochondrial dysfunction, and suppressing osteoclast differentiation; OTUD1 KO leads to enhanced osteoclastogenesis and reduced bone mass. LC-MS/MS combined with Co-IP, ubiquitin linkage assay, whole-body and myeloid-specific KO mice, micro-CT, histomorphometry Theranostics High 40585986
2025 OTUD1 deubiquitinates p53 via K48-dependent deubiquitination through its 300–481 region, stabilizing p53 and promoting a procoagulant gene expression program in endothelial cells; an L357 point mutation of OTUD1 rescues endothelial homeostasis. Co-immunoprecipitation, domain deletion/point mutagenesis (L357), K48-specific ubiquitination assay, ROS manipulation, in vivo thrombosis model Environment international Medium 41967174
2024 OTUD1 binds RACK1 and cleaves K63-linked polyubiquitin chains from RACK1, enhancing RACK1 phosphorylation and modulating downstream MAPKs and NF-κB signaling to promote cardiomyocyte apoptosis after ischemia/reperfusion; RACK1 silencing reverses OTUD1-promoted H/R injury. IP-MS, co-immunoprecipitation, K63-specific deubiquitination assay, RACK1 siRNA rescue, OTUD1 KO mouse (I/R model) Acta pharmacologica Sinica High 40394237
2025 OTUD1 deubiquitinates SMAD7/MADH7 in endometriosis stromal cells, inhibiting fibrosis-related protein expression and reducing endometriosis lesion growth in vivo. Co-immunoprecipitation, ubiquitination assay, in vitro stromal cell model, C57BL/6N mouse in vivo lesion model Molecular human reproduction Medium 40279273

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity. Nature communications 145 29891922
2021 The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity. EMBO reports 129 33393230
2017 Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7. Nature communications 105 29235476
2021 The deubiquitinase OTUD1 inhibits colonic inflammation by suppressing RIPK1-mediated NF-κB signaling. Cellular & molecular immunology 93 34876703
2018 Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by promoting degradation of the MAVS/TRAF3/TRAF6 signalosome. PLoS pathogens 89 29734366
2023 OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes. Theranostics 66 37153745
2022 OTUD1 deubiquitinase regulates NF-κB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways. Cell death & disease 66 35941131
2021 OTUD1 Activates Caspase-Independent and Caspase-Dependent Apoptosis by Promoting AIF Nuclear Translocation and MCL1 Degradation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 65 33898171
2020 OTUD1 Negatively Regulates Type I IFN Induction by Disrupting Noncanonical Ubiquitination of IRF3. Journal of immunology (Baltimore, Md. : 1950) 64 32075857
2021 DDIT3 Targets Innate Immunity via the DDIT3-OTUD1-MAVS Pathway To Promote Bovine Viral Diarrhea Virus Replication. Journal of virology 60 33361422
2022 OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs. International journal of biological sciences 50 35280681
2018 Mutations of deubiquitinase OTUD1 are associated with autoimmune disorders. Journal of autoimmunity 50 30100102
2019 The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein. Cancer cell international 25 31467488
2023 The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 24 37639212
2023 Pleiotropic Roles of a KEAP1-Associated Deubiquitinase, OTUD1. Antioxidants (Basel, Switzerland) 22 36829909
2021 OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9. Journal of immunology (Baltimore, Md. : 1950) 22 33789983
2023 OTUD1 ameliorates cerebral ischemic injury through inhibiting inflammation by disrupting K63-linked deubiquitination of RIP2. Journal of neuroinflammation 21 38012669
2021 Melatonin induces apoptotic cell death through Bim stabilization by Sp1-mediated OTUD1 upregulation. Journal of pineal research 21 34826170
2023 VE-822 upregulates the deubiquitinase OTUD1 to stabilize FHL1 to inhibit the progression of lung adenocarcinoma. Cellular oncology (Dordrecht, Netherlands) 19 36929488
2022 The deubiquitinase OTUD1 inhibits non-small cell lung cancer progression by deubiquitinating and stabilizing KLF4. Thoracic cancer 19 35098684
2024 The deubiquitinase OTUD1 stabilizes NRF2 to alleviate hepatic ischemia/reperfusion injury. Redox biology 17 39079388
2024 Macrophage OTUD1-CARD9 axis drives isoproterenol-induced inflammatory heart remodelling. Clinical and translational medicine 17 39118286
2022 Deubiquitylase OTUD1 confers Erlotinib sensitivity in non-small cell lung cancer through inhibition of nuclear translocation of YAP1. Cell death discovery 16 36182943
2024 OTUD1 promotes isoprenaline- and myocardial infarction-induced heart failure by targeting PDE5A in cardiomyocytes. Biochimica et biophysica acta. Molecular basis of disease 15 38185350
2022 The deubiquitinase OTUD1 noncanonically suppresses Akt activation through its N-terminal intrinsically disordered region. Cell reports 15 36640312
2023 The OTUD1-Notch2-ICD axis orchestrates allogeneic T cell-mediated graft-versus-host disease. Blood 13 36574342
2023 OTUD1 promotes hypertensive kidney fibrosis and injury by deubiquitinating CDK9 in renal epithelial cells. Acta pharmacologica Sinica 12 38110583
2025 OTUD1 exacerbates sepsis-associated encephalopathy by promoting HK2 mitochondrial release to drive microglia pyroptosis. Journal of neuroinflammation 10 40500776
2024 METTL3-mediated m6A modification of OTUD1 aggravates press overload induced myocardial hypertrophy by deubiquitinating PGAM5. International journal of biological sciences 9 39309432
2023 OTUD1 chemosensitizes triple-negative breast cancer to doxorubicin by modulating P16 expression. Pathology, research and practice 9 37257246
2018 SKP2 and OTUD1 govern non-proteolytic ubiquitination of YAP that promotes YAP nuclear localization and activity. Cell stress 8 31225491
2024 The deubiquitinase OTUD1 deubiquitinates TIPE2 and plays a protective role in sepsis-induced lung injury by targeting TAK1-mediated MAPK and NF-κB signaling. Biochemical pharmacology 7 38996928
2022 Deubiquitinase OTUD1 Resolves Stalled Translation on polyA and Rare Codon Rich mRNAs. Molecular and cellular biology 6 36445135
2025 A positive feedback loop of OTUD1 and c-Jun driven by leptin expedites stemness maintenance in ovarian cancer. Oncogene 5 40108305
2024 OTUD1 enhances gastric cancer aggressiveness by deubiquitinating EBV-encoded protein BALF1 to stabilize the apoptosis inhibitor Bcl-2. Biochimica et biophysica acta. Molecular basis of disease 5 38565386
2025 METTL3‑mediated m6A methylation and its impact on OTUD1 expression in chronic obstructive pulmonary disease. Molecular medicine reports 4 40417884
2024 BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in MI/R induced myocyte apoptosis. International journal of cardiology 4 38744338
2023 Herpesvirus latent infection promotes stroke via activating the OTUD1/NF-κB signaling pathway. Aging 4 37695739
2025 Black carp OTUD1 negatively regulates antiviral innate immunity via deubiquitination and degradation of IRF3/7. Fish & shellfish immunology 3 40350101
2025 Combining decitabine with radiotherapy to enhance nasopharyngeal carcinoma radiosensitivity via the TFAP2C-OTUD1-SLC25A11 axis. Cell death & disease 3 40664662
2025 OTUD1 deficiency attenuates myocardial ischemia/reperfusion induced cardiomyocyte apoptosis by regulating RACK1 phosphorylation. Acta pharmacologica Sinica 2 40394237
2025 OTUD1 downregulates PD-L1 expression by deubiquitinating STAT3 and promotes the immune response in ccRCC. Cellular oncology (Dordrecht, Netherlands) 2 40506611
2025 Cardiomyocyte OTUD1 drives diabetic cardiomyopathy via directly deubiquitinating AMPKα2 and inducing mitochondrial dysfunction. Nature communications 2 40683882
2023 Development of an OTUD1 ubiquitin variant inhibitor. The Biochemical journal 2 37589489
2025 The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2. Viruses 1 40007014
2025 OTUD1 inhibits endometriosis fibrosis by deubiquitinating MADH7. Molecular human reproduction 1 40279273
2025 OTUD1 delays wound healing by regulating endothelial function and angiogenesis in diabetic mice. Journal of advanced research 1 40300668
2025 OTUD1 inhibits osteoclast differentiation and osteoclastic bone loss through deubiquitinating and stabilizing PRDX1. Theranostics 1 40585986
2025 Allicin alleviates cerebral ischemia/reperfusion injury by inhibiting neuronal mitochondrial oxidative stress via OTUD1/NRF2 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 1 41172920
2024 OTUD1 regulates cytokine expression and related pathways in goose fatty liver by promoting deubiquitination of its target proteins. Poultry science 1 39437555
2026 OTUD1 Relieves Coxsackievirus-Induced Ferroptosis and Inflammation in Myocardial Cells by Stabilizing NRF2 and Inhibiting NF-κB Signaling. IUBMB life 0 41853919
2026 METTL14 Regulates Myocardial Infarction Progression via m6A-Dependent Modulation of OTUD1-Mediated Deubiquitination of DUSP6. The Kaohsiung journal of medical sciences 0 41910113
2026 From phthalate exposure to venous thrombotic risk: Decoding the DEHP-ROS mediated OTUD1- p53 stabilization loop in endothelium. Environment international 0 41967174
2026 Fluoxetine Alleviates Vascular Cognitive Impairment by Activating the Nrf2/ARE Pathway via Sp1-Mediated OTUD1 Transcription. Free radical research 0 41969155
2025 OTUD1 positively regulates microglia neuroinflammation and promotes the pathogenesis of Alzheimer's disease by deubiquitinating C/EBPβ. Acta pharmacologica Sinica 0 40335710
2025 OTUD1 inhibits macrophage ferroptosis via regulation of AMPK and GSK3β/β-catenin signaling pathways exerting protective effects in sepsis-induced acute lung injury. International immunopharmacology 0 40460602
2025 Apoptotic extracellular vesicles derived from UC-MSCs promote spinal cord injury repair by inhibiting ferroptosis via OTUD1. Free radical biology & medicine 0 41151199
2025 The deubiquitinase OTUD1 orchestrates cisplatin chemosensitivity of non-small cell lung cancer through destabilizing RAD23B/XPC. Oncogene 0 41286308
2024 Pigeon novel-miR-741 targets OTUD1 to inhibit proliferation and promote apoptosis of crop fibroblasts. Poultry science 0 38479099
2024 OTUD1 Deficiency Alleviates LPS-Induced Acute Lung Injury in Mice by Reducing Inflammatory Response. Inflammation 0 39037666