Affinage

OTUD3

OTU domain-containing protein 3 · UniProt Q5T2D3

Length
398 aa
Mass
45.1 kDa
Annotated
2026-06-10
41 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTUD3 is an OTU-family deubiquitinase that removes polyubiquitin from a broad set of substrates to control their stability and activity, positioning it as a context-dependent regulator of tumorigenesis, innate immunity, and metabolism (PMID:26280536, PMID:32679077, PMID:35675826). It hydrolyzes specific ubiquitin linkages—preferentially K6- and K63-linked chains in vitro—and resides largely in the cytoplasm, where it can associate with microtubules (PMID:36503125). Its substrate scope spans tumor-suppressive targets such as PTEN, whose stabilization restrains Akt signaling and transformation (PMID:26280536), p53, which it protects from MDM2-mediated degradation (PMID:32571254), and SMAD7 (PMID:40382618), as well as pro-tumorigenic targets including GRP78 in lung cancer (PMID:31266968) and ACTN4 in hepatocellular carcinoma (PMID:34380780), explaining its dual roles across tissues. In innate immunity OTUD3 acts bidirectionally: it strips K63-linked ubiquitin from MAVS, RIG-I, and MDA5 to dampen RNA-virus signaling (PMID:32679077, PMID:35675783), while binding DNA and cGAS to remove K48-linked ubiquitin and enhance cGAS enzymatic activity, thereby promoting DNA-sensing immunity (PMID:35675783, PMID:36966392), and it restrains pathological STING activation in intestinal fibroblasts (PMID:40680146). OTUD3 also stabilizes IRP2 to govern iron homeostasis, with its loss producing nigral iron accumulation and dopaminergic neurodegeneration (PMID:35490179), and antagonizes the integrated stress response by deubiquitinating eIF2α (PMID:38996071). Its activity is tightly regulated by post-translational control: reversible Lys129 acetylation governs catalytic activity and CBP-driven nuclear translocation toward metabolic substrates such as PPARδ (PMID:32679077, PMID:35675826), CHIP and the RSK3/β-TRCP1 axis target it for degradation (PMID:32483383, PMID:41999888), and PLK1- and GSK3β-mediated phosphorylation redirect its substrate engagement (PMID:38351178, PMID:40181152). An OTUD3 missense variant linked to early-onset diabetes reduces protein stability and catalytic activity (PMID:35675826), and a UC-risk variant predisposes mice to ulcerative colitis-like pathology (PMID:40680146).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2015 High

    Established OTUD3 as a functional deubiquitinase with a defined substrate by showing it directly stabilizes PTEN to restrain Akt-driven transformation, framing OTUD3 as a tumor suppressor.

    Evidence Co-IP, in vitro DUB assay, transgenic mice, and cancer-associated loss-of-function mutants

    PMID:26280536

    Open questions at the time
    • Linkage specificity on PTEN not defined
    • Whether PTEN is the dominant substrate in all tissues unresolved
  2. 2019 High

    Revealed that OTUD3 can also be pro-tumorigenic by stabilizing GRP78, showing its role is substrate- and tissue-context dependent rather than uniformly tumor-suppressive.

    Evidence Reciprocal Co-IP, ubiquitination assay, and OTUD3 knockout in a KrasG12D lung adenocarcinoma mouse model

    PMID:31266968

    Open questions at the time
    • Mechanism reconciling opposing PTEN vs GRP78 roles not addressed
    • Ubiquitin linkage on GRP78 not specified
  3. 2020 High

    Identified acetylation at Lys129 as a switch controlling OTUD3 catalytic activity and connected OTUD3 to innate antiviral signaling via K63-linked deubiquitination of MAVS.

    Evidence In vitro DUB assay, K129 acetylation mutants, SIRT1 manipulation, and OTUD3-deficient mice with viral infection

    PMID:32679077

    Open questions at the time
    • How acetylation alters catalytic geometry not structurally defined
    • CBP as the writer not established in this study
  4. 2020 Medium

    Extended the tumor-suppressor model by showing OTUD3 stabilizes p53 against MDM2, and identified CHIP as an E3 ligase that degrades OTUD3, defining its turnover control.

    Evidence Co-IP, GST pulldown, ubiquitination and half-life assays (p53); reciprocal Co-IP and ubiquitination with CHIP mutants

    PMID:32483383 PMID:32571254

    Open questions at the time
    • Single-lab findings without in vivo confirmation
    • Linkage type of CHIP-mediated chains not specified
  5. 2022 High

    Defined OTUD3's intrinsic linkage preference (K6/K63), cytoplasmic/microtubule localization, and roles in iron homeostasis and DNA/RNA virus sensing, establishing the bidirectional immune function and a neurodegeneration phenotype.

    Evidence Linkage-specific in vitro DUB assays, fractionation/IF, IRP2 and RIG-I/MDA5/cGAS ubiquitination assays, OTUD3 knockout mice and zebrafish, Xenopus knockdown

    PMID:35490179 PMID:35675783 PMID:36503125

    Open questions at the time
    • How a single DUB selects opposing immune substrates (RIG-I vs cGAS) mechanistically unclear
    • Microtubule binding functional consequence undefined
  6. 2022 High

    Showed acetylation directs OTUD3 to the nucleus to stabilize PPARδ for metabolic gene control, and linked an OTUD3 mutation to early-onset diabetes, broadening OTUD3 beyond cytoplasmic functions.

    Evidence Otud3-/- mice on high-fat diet, acetylation mutants, nuclear fractionation/IF, PPARδ ubiquitination assay with agonist rescue, human family mutation

    PMID:35675826

    Open questions at the time
    • Acetyltransferase/deacetylase pairing for nuclear translocation incomplete
    • Causality of the c.863G>A variant at population scale not established
  7. 2023 Medium

    Mechanistically deepened the cGAS axis by demonstrating OTUD3 directly binds DNA to be recruited to cGAS-DNA complexes and enhances cGAS enzymatic activity beyond mere stabilization.

    Evidence TurboID proximity labeling, Co-IP, in vitro DNA-binding and cGAS activity assays, viral infection

    PMID:36966392

    Open questions at the time
    • Structural basis of DNA binding not resolved
    • Single-lab enzymatic enhancement awaits independent confirmation
  8. 2024 High

    Diversified substrate repertoire and regulatory inputs: OTUD3 antagonizes the integrated stress response via K27-linked deubiquitination of eIF2α, and phosphorylation by PLK1 (Ser326) and stabilization of PLK1, KPTN, and SLC7A11 connect OTUD3 to mTORC1, ferroptosis, and cell-cycle control.

    Evidence Linkage-specific ubiquitination assays, knockout HCC mice with ISRIB rescue, kinase assays, phospho-site mutants, and functional ferroptosis/mTORC1 readouts

    PMID:38288086 PMID:38351178 PMID:38996071 PMID:40462502 PMID:40716486

    Open questions at the time
    • Many substrate relationships rest on single-lab data
    • How phosphorylation reshapes substrate selection not generalized
  9. 2025 Medium

    Mapped degron-based turnover (RSK3/β-TRCP1 via an ESG motif), GSK3β priming for ARID3A engagement, and expanded immune/metabolic/cancer substrates (STING, SMAD7, PPARγ, MYL12A/PD-L1), reinforcing OTUD3 as a heavily PTM-gated hub with therapeutic targetability.

    Evidence Phospho-degron mutagenesis with mTORC2 inhibitors, site-specific ubiquitination assays, knock-in UC-variant mice with fecal transplant, catalytic-mutant invasion assays, and Rupatadine competitive-binding/T-cell exhaustion assays

    PMID:39097608 PMID:40181152 PMID:40382618 PMID:40680146 PMID:40886936 PMID:41999888

    Open questions at the time
    • Disease-variant causality (UC) established only in mouse models
    • PPARγ substrate relationship is low-confidence with limited direct ubiquitination detail
  10. 2026 Medium

    Localized OTUD3 to additional compartments and pathways: ECSIT-dependent mitochondrial recruitment to stabilize SIRT3, and stabilization of BHLHE22 and the ER-phagy receptor TEX264, linking OTUD3 to mitochondrial protection, ER-phagy, and tumor suppression.

    Evidence Mitochondria-targeted transgenic mice with fractionation and SIRT3 ubiquitination assay; Co-IP, catalytic mutants, transcriptional and ER-phagy flux readouts in cancer models

    PMID:41484895 PMID:41640247 PMID:41763483

    Open questions at the time
    • Mitochondrial vs nuclear vs cytoplasmic targeting determinants not unified
    • Single-lab substrate claims lacking cross-validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OTUD3 selects among its many substrates and opposing roles in a given tissue—and whether a unifying structural or regulatory logic governs its linkage specificity and subcellular partitioning—remains unresolved.
  • No structural model integrating PTM-driven substrate switching
  • No systematic comparison of which substrate dominates per tissue
  • Therapeutic window of OTUD3 inhibition across opposing functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 4 GO:0003677 DNA binding 1
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 5 R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 1
Partners
CGASCHIPGRP78IRP2MAVSP53PPARDPTEN

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 OTUD3 directly interacts with PTEN, de-polyubiquitylates it, and stabilizes PTEN protein levels. Depletion of OTUD3 leads to activation of Akt signaling and promotes cellular transformation. Loss-of-function OTUD3 mutations found in human cancers either abolish catalytic activity or attenuate interaction with PTEN. Co-immunoprecipitation, ubiquitination assay, OTUD3 transgenic mice, loss-of-function mutant analysis, in vitro deubiquitylation assay Nature cell biology High 26280536
2019 OTUD3 interacts with, deubiquitylates, and stabilizes GRP78 (glucose-regulated protein 78 kDa) in lung cancer cells, promoting lung tumorigenesis. In vivo deletion of OTUD3 slows KrasG12D-driven lung adenocarcinoma progression. Co-immunoprecipitation, ubiquitination assay, OTUD3 knockout mice with KrasG12D lung cancer model, knockdown/rescue experiments Nature communications High 31266968
2020 OTUD3 directly hydrolyzes K63-linked polyubiquitination of MAVS to suppress innate antiviral immune signaling. The catalytic activity of OTUD3 is regulated by acetylation of Lys129; SIRT1 removes this acetylation upon virus infection, inactivating OTUD3 and permitting antiviral immunity. In vitro deubiquitylation assay, acetylation site mutagenesis (K129 mutants), OTUD3-deficient mice, SIRT1 knockdown/overexpression, viral infection models Molecular cell High 32679077
2020 OTUD3 directly interacts with p53, deubiquitylates it, and protects p53 from MDM2-mediated ubiquitination and degradation. The catalytically inactive OTUD3 mutant fails to stabilize p53. The interaction occurs through the amino-terminal OTU region of OTUD3. Co-immunoprecipitation, GST pulldown, ubiquitination assay, half-life analysis, catalytic mutant (inactive mutant), proliferation and apoptosis assays BMC cancer Medium 32571254
2020 CHIP (carboxyl terminus of Hsc70-interacting protein) is an E3 ubiquitin ligase for OTUD3; CHIP interacts with OTUD3, polyubiquitylates it, and promotes OTUD3 proteasomal degradation. Co-immunoprecipitation, ubiquitination assay, CHIP knockdown/overexpression, CHIP catalytic mutant analysis Cell death and differentiation Medium 32483383
2021 OTUD3 directly interacts with ZFP36 and stabilizes it by inhibiting FBXW7-mediated K48-linked polyubiquitination. ZFP36 in turn binds VEGF-C 3'-UTR and recruits RNA degrading complex to promote VEGF-C mRNA decay. Co-immunoprecipitation, ubiquitination assay, RNA decay assay, ZFP36 rescue experiments, esophageal cancer cell and in vivo models Nature communications Medium 34853315
2021 OTUD3 directly binds ACTN4 (alpha-actinin 4) and deubiquitinates it to stabilize ACTN4 protein, driving hepatocellular carcinoma growth and metastasis. Mass spectrometry identification, Co-immunoprecipitation, ubiquitination assay, gain- and loss-of-function assays, xenograft mouse model Aging Medium 34380780
2022 OTUD3 functions as a deubiquitylase for IRP2 (iron regulatory protein 2), interacting with IRP2 in the cytoplasm, removing polyubiquitin to stabilize IRP2 in an iron-independent manner. OTUD3 knockout mice display nigral iron accumulation, motor deficits, and nigrostriatal dopaminergic neurodegeneration resembling Parkinson's disease pathology. Co-immunoprecipitation, ubiquitination assay, OTUD3 knockout mouse model, neurochemical and behavioral analyses Cell death & disease High 35490179
2022 OTUD3 binds to RIG-I and MDA5, removing K63-linked ubiquitination to reduce their binding to viral RNA and the adaptor MAVS, suppressing RNA virus-triggered innate immunity. Simultaneously, OTUD3 associates with cGAS and removes K48-linked ubiquitination at Lys279, stabilizing cGAS and enhancing its DNA-binding ability, thus promoting DNA virus-triggered innate immunity. Co-immunoprecipitation, ubiquitination assay with linkage-specific analysis, Otud3-deficient mice and zebrafish, viral infection models (RNA and DNA viruses) Cell reports High 35675783
2022 OTUD3 cleaves preferentially K6- and K63-linked polyubiquitin chains (not primarily degradative linkages). In cells, OTUD3 is present in the cytoplasm where it can bind to microtubules. In Xenopus embryos, Otud3 deficiency impairs cranial neural crest-derived structures and causes movement defects. In vitro deubiquitylation assay with linkage-specific ubiquitin chains, cellular fractionation/immunofluorescence for microtubule co-localization, Xenopus morpholino knockdown Biochimica et biophysica acta. Gene regulatory mechanisms Medium 36503125
2022 OTUD3 is regulated by glucose and fatty acid signals through CBP-dependent acetylation, which promotes OTUD3 nuclear translocation. In the nucleus, OTUD3 stabilizes PPARδ by deubiquitination, regulating genes involved in glucose and lipid metabolism and oxidative phosphorylation. A c.863G>A OTUD3 mutation reduces protein stability and catalytic activity and is found in a family with early-onset diabetes. Otud3-/- mouse model with high-fat diet, acetylation mutant analysis, nuclear fractionation/immunofluorescence, ubiquitination assay for PPARδ, PPARδ agonist rescue experiment Cell metabolism High 35675826
2023 OTUD3 is recruited to cytosolic cGAS-DNA complexes through its ability to directly bind DNA. In addition to stabilizing cGAS (removing ubiquitin to prevent degradation), OTUD3 enhances cGAS enzymatic activity, thereby promoting anti-DNA virus immune response. Proximity labeling (TurboID) of cGAS to identify interactors, Co-immunoprecipitation, in vitro DNA-binding assay, cGAS enzymatic activity assay, viral infection assay Cell reports Medium 36966392
2023 OTUD3 regulates the ubiquitination level of Fortilin through its OTU domain, stabilizing Fortilin, which in turn maintains Fortilin-IRE1α interaction. OTUD3 knockdown reduces Fortilin-IRE1α interaction, enhancing IRE1α activity and promoting ER stress-induced apoptosis of dopaminergic neurons. Co-immunoprecipitation, ubiquitination assay, OTUD3 knockout mouse histology, IRE1α inhibitor rescue (STF-083010), ER stress marker analysis (PDI, XBP1s) Antioxidants (Basel, Switzerland) Medium 37107185
2024 OTUD3 is a deubiquitylase of eIF2α (eukaryotic initiation factor 2α), removing K27-linked polyubiquitylation from eIF2α. This decreases interactions between eIF2α and the kinase EIF2AK3 (PERK), thereby antagonizing the integrated stress response (ISR) and suppressing liver cancer progression. Co-immunoprecipitation, ubiquitination assay with K27-linkage specificity, OTUD3 deficient mice with N-nitrosodiethylamine-induced HCC, ISRIB pharmacological rescue Cell reports High 38996071
2024 PLK1 mediates phosphorylation of OTUD3 at Ser326, which enhances OTUD3 binding to and deubiquitination of YY1 transcription factor, stabilizing YY1 and promoting colorectal cancer progression. Co-immunoprecipitation, ubiquitination assay, PLK1 kinase assay, phospho-site mutant analysis (S326), colorectal cancer cell proliferation assays Cell death & disease Medium 38351178
2024 OTUD3 deubiquitinates SLC7A11, protecting it from proteasomal degradation, thereby promoting cystine transport, reducing intracellular ROS levels, and suppressing ferroptosis to drive sunitinib resistance in clear cell renal cell carcinoma. Co-immunoprecipitation, ubiquitination assay, ferroptosis assay (ROS levels), sunitinib resistance cell models and in vivo xenograft Cancer letters Medium 40716486
2024 OTUD3 deubiquitinates and stabilizes KPTN (kaptin), acting through its OTU domain. Ubiquitination of KPTN primarily occurs at lysine 49 and is a non-degradative functional modification. OTUD3 promotes GATOR1 lysosomal localization via KPTN, thereby suppressing mTORC1 signaling activation independent of PTEN. In vivo ubiquitination assay, Co-immunoprecipitation, CRISPR/Cas9 OTUD3 knockout, immunofluorescence for GATOR1 localization, NMR, mTORC1 signaling readout (S6K phosphorylation) Frontiers in pharmacology Medium 38288086
2024 OTUD3 deubiquitinates PLK1 via K48-linked ubiquitin chains, stabilizing PLK1 protein. Stabilized PLK1 activates the PI3K/AKT signaling pathway, reducing ferroptosis after cerebral ischemia-reperfusion injury. OTUD3 binds the amino acid sequence 35-305 of PLK1. Co-immunoprecipitation-mass spectrometry, ubiquitination assay (K48-linkage specific), OTUD3 overexpression/knockdown in OGD/R neuron model, PLK1 inhibitor rescue, in vivo cerebral I/R mouse model Clinical and translational medicine Medium 40462502
2025 OTUD3 deubiquitinates STING in intestinal fibroblasts to suppress pathological STING activation triggered by microbial cyclic GMP-AMP (cGAMP). Mice harboring a UC-risk missense variant in Otud3 show pathological features of ulcerative colitis after fecal microbiota transplantation from UC patients. OTUD3 knockout and missense variant knock-in mice, fecal microbiota transplantation, ubiquitination assay for STING, intestinal fibroblast functional assays Science immunology High 40680146
2025 GSK3β phosphorylates OTUD3 at Ser9, which enhances OTUD3 affinity for ARID3A and further stabilizes ARID3A by removing ubiquitin chains at K240 and K329 of ARID3A, promoting cholangiocarcinoma progression. Co-immunoprecipitation, ubiquitination assay, site-specific mutagenesis (K240/K329 of ARID3A, Ser9 of OTUD3), in vivo and in vitro CCA proliferation/metastasis assays Oncogene Medium 40181152
2025 The E3 ubiquitin ligase β-TRCP1 targets OTUD3 for ubiquitination and proteasomal degradation through RSK3-mediated phosphorylation of a conserved 'ESG' degron motif in OTUD3. Cytosolic DNA challenge inactivates the β-TRCP1/RSK3 pathway (via mTORC2 signaling, independently of canonical Ras/MEK/ERK and DNA damage kinases), resulting in OTUD3 stabilization and enhanced cGAS activation. Co-immunoprecipitation, ubiquitination assay, phospho-degron mutagenesis (ESG motif), RSK3 kinase assay, mTORC2 inhibitor experiments, viral/DNA challenge cell assays The Journal of biological chemistry Medium 41999888
2025 OTUD3 deubiquitinates and stabilizes SMAD7, thereby inhibiting TGF-β signaling, suppressing EMT, and reducing breast cancer cell invasion. Catalytically inactive OTUD3 (C76 site mutant) fails to regulate BHLHE22 and SMAD7 protein stability. Co-immunoprecipitation, ubiquitination assay, catalytic mutant (C76), luciferase reporter assay for TGF-β pathway, transwell invasion assay, 3D matrigel culture Cancer cell international Medium 40382618
2025 OTUD3 deubiquitinates MYL12A and PD-L1 to enhance cell survival and immune evasion (CD8+ T cell exhaustion) in DLBCL. The OTUD3 inhibitor Rupatadine competitively binds OTUD3 and diminishes deubiquitination of both MYL12A and PD-L1. Co-immunoprecipitation, ubiquitination assay, competitive binding assay for Rupatadine-OTUD3, CD8+ T cell co-culture exhaustion assay Cell death & disease Medium 39097608
2025 OTUD3 deubiquitinates and stabilizes PPARγ in retinal pigment epithelium cells, protecting against oxidative stress and inflammation in diabetic retinopathy. OTUD3 knockdown/knockout mouse model, ubiquitination assay for PPARγ, PPARγ agonist rescue, ROS/apoptosis assays in RPE cell lines Life sciences Low 40886936
2026 OTUD3 deubiquitinates and stabilizes BHLHE22 transcription factor in triple-negative breast cancer, suppressing tumor progression. The catalytic C76 mutant of OTUD3 fails to stabilize BHLHE22. BHLHE22 mediates the antitumor effect of OTUD3 by transcriptionally inhibiting CDT1. Co-immunoprecipitation, ubiquitination assay, catalytic site mutant (C76), dual luciferase reporter assay for CDT1 transcription, mRNA-seq, in vivo xenograft Breast cancer research : BCR Medium 41484895
2026 Mitochondrial ECSIT promotes the localization of OTUD3 to mitochondria, where OTUD3 deubiquitinates SIRT3 to stabilize it, thereby inhibiting mtDNA oxidation and alleviating MASH-associated metabolic disorders. ECSIT mitochondria-targeted transgenic mice, OTUD3 mitochondrial fractionation/immunofluorescence, ubiquitination assay for SIRT3, HFHC and MCD diet MASH models Advanced science Medium 41640247
2026 OTUD3 deubiquitinates and stabilizes TEX264, a receptor for ER-phagy. Stabilized TEX264 enables ER-phagy-mediated degradation of KDM5B in lung cancer cells treated with teniposide. OTUD3 silencing dampens teniposide-driven ER-phagy and KDM5B inhibition. Co-immunoprecipitation, ubiquitination assay, OTUD3 knockdown, ER-phagy flux assay, lung cancer organoid and xenograft models European journal of pharmacology Medium 41763483

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis. Nature cell biology 165 26280536
2019 The deubiquitylase OTUD3 stabilizes GRP78 and promotes lung tumorigenesis. Nature communications 110 31266968
2020 Acetylation-Dependent Deubiquitinase OTUD3 Controls MAVS Activation in Innate Antiviral Immunity. Molecular cell 84 32679077
2021 Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer. Nature communications 51 34853315
2020 Ubiquitin ligase CHIP regulates OTUD3 stability and suppresses tumour metastasis in lung cancer. Cell death and differentiation 50 32483383
2022 Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses. Cell metabolism 45 35675826
2020 Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells. BMC cancer 37 32571254
2022 Deubiquitylase OTUD3 prevents Parkinson's disease through stabilizing iron regulatory protein 2. Cell death & disease 36 35490179
2022 Opposing effects of deubiquitinase OTUD3 in innate immunity against RNA and DNA viruses. Cell reports 28 35675783
2021 The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma. Aging 26 34380780
2020 miR-520h Stimulates Drug Resistance to Paclitaxel by Targeting the OTUD3-PTEN Axis in Breast Cancer. BioMed research international 26 32775453
2023 Discovery of an OTUD3 inhibitor for the treatment of non-small cell lung cancer. Cell death & disease 18 37369659
2024 Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression. Cell death & disease 17 38351178
2024 Deubiquitylase OTUD3 regulates integrated stress response to suppress progression and sorafenib resistance of liver cancer. Cell reports 17 38996071
2020 The expression change of OTUD3-PTEN signaling axis in glioma cells. Annals of translational medicine 14 32395534
2023 Proximity labeling reveals OTUD3 as a DNA-binding deubiquitinase of cGAS. Cell reports 13 36966392
2024 Rolapitant treats lung cancer by targeting deubiquitinase OTUD3. Cell communication and signaling : CCS 12 38539203
2023 Deubiquitinase OTUD3: a double-edged sword in immunity and disease. Frontiers in cell and developmental biology 12 37829187
2023 Bone Marrow Stromal Cell-Secreted Extracellular Vesicles Containing miR-34c-5p Alleviate Lung Injury and Inflammation in Bronchopulmonary Dysplasia Through Promotion of PTEN Degradation by Targeting OTUD3. Immunological investigations 11 37310728
2025 OTUD3-mediated stabilization of SLC7A11 drives sunitinib resistance by suppressing ferroptosis in clear cell renal cell carcinoma. Cancer letters 9 40716486
2024 Rupatadine-inhibited OTUD3 promotes DLBCL progression and immune evasion through deubiquitinating MYL12A and PD-L1. Cell death & disease 9 39097608
2022 Silencing of LncRNA SNHG6 protects trophoblast cells through regulating miR-101-3p/OTUD3 axis in unexplained recurrent spontaneous abortion. Journal of molecular histology 8 36173586
2023 Deubiquitylase OTUD3 Mediates Endoplasmic Reticulum Stress through Regulating Fortilin Stability to Restrain Dopaminergic Neurons Apoptosis. Antioxidants (Basel, Switzerland) 7 37107185
2025 OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation. Science immunology 6 40680146
2024 The deubiquitinase OTUD3 stabilizes IRP2 expression to reduce hippocampal neuron ferroptosis via the p53/PTGS2 pathway to ameliorate cerebral ischemia-reperfusion injury. European journal of medical research 6 39415292
2022 OTUD3: A Lys6 and Lys63 specific deubiquitinase in early vertebrate development. Biochimica et biophysica acta. Gene regulatory mechanisms 6 36503125
2024 OTUD3 suppresses the mTORC1 signaling by deubiquitinating KPTN. Frontiers in pharmacology 5 38288086
2022 Prevalence and clinical characteristics of T2DM patients with OTUD3 gene rs78466831 SNP at a single academic center in China. Frontiers in endocrinology 5 36531510
2025 OTUD3 inhibits breast cancer cell metastasis by regulating TGF-β pathway through deubiquitinating SMAD7. Cancer cell international 4 40382618
2025 The deubiquitinase OTUD3 plays a neuroprotective role by reducing ferroptosis induced by cerebral ischaemia reperfusion via stabilizing PLK1 via deubiquitination. Clinical and translational medicine 2 40462502
2025 Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma. Oncogene 1 40181152
2025 Dysregulation of the TNF-α-OTUD3-PPARγ signaling axis exacerbates retinal oxidative stress and inflammation in diabetic retinopathy. Life sciences 1 40886936
2025 Roles of Deubiquitinases OTUD3 and OTUD5 in Inflammatory Bowel Diseases. International journal of molecular sciences 1 41155222
2026 BHLHE22, targeted by deubiquitinating enzyme OTUD3, exerts an antitumor role in triple-negative breast cancer progression via transcriptionally inhibiting CDT1. Breast cancer research : BCR 0 41484895
2026 Targeted Mitochondrial ECSIT Overexpression Attenuates MASH by Increasing OTUD3 Expression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41640247
2026 OTUD3-mediated deubiquitination licenses TEX264 to orchestrate ER-phagy for KDM5B degradation in teniposide lung cancer therapy. European journal of pharmacology 0 41763483
2026 The E3 ligase β-TRCP1 earmarks OTUD3 for destruction to fine-tune cGAS activation. The Journal of biological chemistry 0 41999888
2025 Pathogenic OTUD3 Mutations Predispose to Ulcerative Colitis Due to Barrier Dysfunction. Cellular and molecular gastroenterology and hepatology 0 41067575
2025 A Variant of OTUD3 in Early-Onset Parkinsonism. Neuropathology and applied neurobiology 0 41146402
2025 The dual role of OTUD3 in cancer: mechanisms and therapeutic implications. Cancer cell international 0 41437362
2024 Research progress in deubiquitinase OTUD3. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 0 39788523

Missed literature

Know a paper Affinage missed for OTUD3? Flag it for the maintainers and the community.

No submissions yet.