Affinage

OTUB2

Ubiquitin thioesterase OTUB2 · UniProt Q96DC9

Length
234 aa
Mass
27.2 kDa
Annotated
2026-06-10
43 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTUB2 is an OTU-family cysteine deubiquitinase that controls the abundance and signaling output of diverse substrates by trimming polyubiquitin chains—predominantly K48-linked—and thereby protecting target proteins from proteasomal degradation (PMID:24560272, PMID:40021931, PMID:39358938). Its catalytic cysteine C51 is required for activity, and removal of K48 chains rather than chain processing per se underlies most of its documented stabilizing functions (PMID:40021931, PMID:39358938). A defining regulatory layer is its own poly-SUMOylation on lysine 233, which is induced by EGF and oncogenic KRAS and enables OTUB2 to recognize substrates such as YAP/TAZ through a SUMO-interacting motif, deubiquitinating and stabilizing them to activate Hippo/YAP-TAZ transcriptional output independently of canonical Hippo regulation (PMID:30472188). Through substrate stabilization OTUB2 acts as a node across multiple pathways: it deubiquitinates the E3 ligases TRAF3 and TRAF6 to negatively regulate virus-triggered type I interferon and NF-κB induction (PMID:19996094), stabilizes RIPK2 to promote NOD2 signaling in macrophages and intestinal inflammation (PMID:39358938), stabilizes RIPK3 to potentiate neuronal necroptosis after ischemic stroke (PMID:40021931), and stabilizes β-Catenin to enhance Wnt/TCF transcriptional programs (PMID:38058843). In tumor settings OTUB2 drives glycolytic and Warburg-effect metabolism by stabilizing or activating substrates including U2AF2, PKM2, and SP1 (PMID:30662561, PMID:34671086, PMID:39210373), and promotes immune evasion by stabilizing PD-L1 in the endoplasmic reticulum, an activity that is druggable with a deubiquitinase inhibitor that lowers PD-L1 and suppresses tumor growth (PMID:38167274). Beyond signaling, OTUB2 fine-tunes the DNA double-strand break response by suppressing RNF8-mediated K63 ubiquitination and limiting 53BP1/RAP80 accumulation, biasing repair toward homologous recombination (PMID:24560272). No experimentally validated structural model exists; computational work indicates the OTU catalytic triad is disordered until ubiquitin binding triggers a productive rearrangement (PMID:32265297).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 High

    Established the first cellular function of OTUB2 by showing it deubiquitinates the innate-immune E3 ligases TRAF3 and TRAF6 to restrain antiviral signaling.

    Evidence Reciprocal Co-IP plus overexpression/knockdown with IRF3, NF-κB, and IFNB1 reporter assays

    PMID:19996094

    Open questions at the time
    • Ubiquitin chain linkage specificity on TRAF3/TRAF6 not defined
    • No catalytic mutant or in vivo model in this study
  2. 2014 High

    Placed OTUB2 in the DNA damage response, showing it tempers DSB-induced ubiquitination to influence repair pathway choice.

    Evidence Depletion, catalytically dead mutants, DSB focus imaging (53BP1, RAP80), and HR-vs-NHEJ reporter assays

    PMID:24560272

    Open questions at the time
    • Direct K63 chain disassembly kinetics at chromatin not resolved
    • Recruitment mechanism to DSB sites unknown
  3. 2018 High

    Revealed OTUB2's own poly-SUMOylation (K233) as a switch that licenses substrate recognition, linking it to oncogenic Hippo/YAP-TAZ activation downstream of EGF/KRAS.

    Evidence Gain-of-function metastasis screen, Co-IP, SIM/SUMO mutagenesis, and SUMOylation assays in cancer cells

    PMID:30472188

    Open questions at the time
    • SUMO E3 ligase responsible for OTUB2 modification not identified
    • Whether SIM-dependent recognition generalizes to non-YAP substrates untested
  4. 2018 Medium

    Extended OTUB2 substrate stabilization to Hedgehog signaling via Gli2 deubiquitination, connecting it to differentiation programs.

    Evidence Co-IP, in vitro deubiquitination with catalytic mutants, CHX chase, MG-132 rescue, osteogenesis assays

    PMID:30241937

    Open questions at the time
    • Chain linkage on Gli2 not specified
    • Single-lab finding without in vivo validation
  5. 2019 Medium

    Identified a metabolic role through U2AF2 stabilization driving the Warburg effect and AKT/mTOR signaling in lung cancer.

    Evidence Co-IP/MS, ubiquitination assays, glycolysis and AKT/mTOR readouts

    PMID:30662561

    Open questions at the time
    • Catalytic dependence not confirmed with active-site mutant
    • Single tumor context
  6. 2020 Low

    Provided a structural rationale for OTUB2 catalysis, showing its OTU triad is disordered until ubiquitin binding induces a competent conformation.

    Evidence Molecular dynamics simulations comparing OTUB2 with OTUB1 (computational)

    PMID:32265297

    Open questions at the time
    • Computational prediction only; no experimental structure or mutagenesis validation
    • Functional consequence of substrate-induced ordering untested
  7. 2021 Medium

    Showed OTUB2 enhances glycolysis by shielding PKM2 from its E3 ligase Parkin, a non-canonical mechanism of blocking ubiquitination rather than removing chains.

    Evidence Co-IP, ubiquitination assays, glycolysis readouts, OTUB2 knockout in vivo in colorectal cancer

    PMID:34671086

    Open questions at the time
    • Whether the effect requires OTUB2 catalytic activity vs steric blockade unclear
    • Single-lab context
  8. 2022 Medium

    Expanded the substrate repertoire to transcription and chromatin factors (β-Catenin, SP1, STAT1) coupling OTUB2 to Wnt, glycolytic, and tumor-suppressive transcriptional programs.

    Evidence Reciprocal Co-IP/LC-MS, K48-specific ubiquitination assays, catalytic mutants, ChIP-qPCR and luciferase reporters; in vivo models

    PMID:36288705 PMID:36858343 PMID:38058843 PMID:39210373

    Open questions at the time
    • Context-dependent oncogenic vs tumor-suppressive roles not mechanistically reconciled
    • Substrate selectivity determinants undefined
  9. 2024 High

    Defined OTUB2 as a druggable stabilizer of PD-L1 in the ER, establishing a tumor-immune-evasion role and proof-of-concept pharmacology.

    Evidence Co-IP, genetic KO with PD-L1 flow cytometry, T-cell cytotoxicity, and a deubiquitinase inhibitor in vivo across cancer types

    PMID:38167274

    Open questions at the time
    • PD-L1 ubiquitin linkage type not specified
    • Responsible E3 ligase for PD-L1 not identified
  10. 2024 High

    Demonstrated in vivo, active-site (C51)-dependent K48 deubiquitination of RIPK2, placing OTUB2 in NOD2 innate signaling and intestinal inflammation.

    Evidence Otub2 knockout mice, bone marrow chimeras, Co-IP, K48-specific ubiquitination assays, C51 mutant, cytokine and colitis readouts

    PMID:39358938

    Open questions at the time
    • Whether SUMOylation gates RIPK2 recognition untested
    • Upstream control of OTUB2 in macrophages unknown
  11. 2025 High

    Showed C51-dependent K48 deubiquitination of RIPK3 drives neuronal necroptosis after stroke, identifying OTUB2 as a neuroprotective drug target.

    Evidence OTUB2 KO mice, C51 mutant, K48-specific ubiquitination assays, pharmacological inhibition in stroke model and human brain organoids

    PMID:40021931

    Open questions at the time
    • Trigger for OTUB2 engagement of RIPK3 during ischemia undefined
    • Relationship to RIPK1/MLKL axis not detailed
  12. 2025 Medium

    Broadened the physiological reach of OTUB2 to vascular calcification, cardiac hypertrophy, and pancreatic β-cell function, including non-deubiquitinase outputs such as Rac1/MEK-ERK activation.

    Evidence AAV9 tissue-specific KO/overexpression, K48-specific ubiquitination assays, CUT&RUN-qPCR, Rac1 GTP pulldown with pharmacological rescue, Co-IP/MS in β-cells, glucose tolerance tests

    PMID:39776804 PMID:41329260 PMID:41914276

    Open questions at the time
    • Direct substrate(s) for Rac1 activation not established
    • Mechanism linking OTUB2 to K+ channel subunits/insulin secretion unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OTUB2 achieves substrate selectivity across its very broad target set, and whether SUMOylation-gated SIM recognition is a general versus YAP-specific mechanism, remains unresolved.
  • No co-crystal/cryo-EM structure with ubiquitin or substrate
  • No systematic substrate-specificity or linkage-preference map
  • Rules governing oncogenic vs tumor-suppressive context unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-73894 DNA Repair 1
Partners
CTNNB1PD-L1RIPK2RIPK3TRAF3TRAF6WWTR1YAP1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 OTUB2 deubiquitinates and stabilizes YAP and TAZ, activating them independently of the Hippo pathway. OTUB2 is poly-SUMOylated on lysine 233, and this SUMOylation enables it to bind YAP/TAZ via a novel SUMO-interacting motif (SIM) in YAP/TAZ. EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation to activate YAP/TAZ. Gain-of-function cancer metastasis screen, co-immunoprecipitation, mutagenesis, SUMOylation assays Molecular cell High 30472188
2009 OTUB2 interacts with TRAF3 and TRAF6 (E3 ubiquitin ligases required for IRF3 and NF-κB activation, respectively) and mediates their deubiquitination, thereby negatively regulating virus-triggered type I IFN induction. Overexpression inhibited IRF3 and NF-κB activation; knockdown had the opposite effect. Co-immunoprecipitation, overexpression/knockdown with reporter assays for IRF3, NF-κB, and IFNB1 The Journal of biological chemistry High 19996094
2014 OTUB2 suppresses RNF8-mediated L3MBTL1 ubiquitination and K63-linked ubiquitin chain formation at DNA double-strand breaks in a deubiquitinating-activity-dependent manner, thereby fine-tuning the speed of DSB-induced ubiquitination and promoting homologous recombination over NHEJ by limiting 53BP1/RAP80 accumulation and DSB-end protection. Depletion of OTUB2 (siRNA/shRNA), deubiquitination activity-dead mutants, immunofluorescence of DSB foci (53BP1, RAP80), ubiquitination assays, DNA repair pathway assays (HR vs. NHEJ reporters) Molecular cell High 24560272
2019 OTUB2 directly binds and deubiquitinates U2AF2 (a splicing factor), stabilizing it against proteasomal degradation, and thereby promotes the Warburg effect and AKT/mTOR pathway activation in non-small cell lung cancer. Co-immunoprecipitation, mass spectrometry, ubiquitination assays, knockdown/overexpression with glycolysis readouts and AKT/mTOR pathway markers Theranostics Medium 30662561
2021 OTUB2 directly interacts with PKM2 and inhibits its ubiquitination by blocking the interaction between PKM2 and its E3 ligase Parkin, thereby enhancing PKM2 activity and promoting aerobic glycolysis in colorectal cancer. Co-immunoprecipitation, ubiquitination assays, glycolysis metabolic readouts, OTUB2 knockout in vivo Oncogene Medium 34671086
2024 OTUB2 directly interacts with PD-L1 in the endoplasmic reticulum and removes ubiquitin modifications that would otherwise target PD-L1 for degradation, thereby stabilizing PD-L1 on the tumor cell surface and promoting immune evasion. A small-molecule inhibitor of OTUB2's deubiquitinase activity (without disrupting the OTUB2–PD-L1 interaction) reduces PD-L1 levels and suppresses tumor growth. Co-immunoprecipitation, genetic deletion of OTUB2 with flow cytometry for PD-L1, T cell cytotoxicity assays, pharmacological OTUB2 inhibitor in vivo Nature communications High 38167274
2018 OTUB2 co-immunoprecipitates with the transcription factor Gli2, deubiquitinates it in vivo and in vitro (with catalytic mutants losing this activity), and stabilizes it against proteasomal degradation, thereby promoting Hedgehog signaling. Knockdown of OTUB2 suppresses osteogenic differentiation of MSCs. Co-immunoprecipitation, in vitro deubiquitination assay with OTUB2 catalytic mutants, cycloheximide chase, MG-132 rescue, osteogenesis assays Biochemical and biophysical research communications Medium 30241937
2020 Molecular dynamics simulations revealed that OTUB2 possesses a catalytic triad characteristic of OTU cysteine proteases, but unlike OTUB1, its catalytic triad is disordered in the absence of ubiquitin and only rearranges to a catalytically competent state upon ubiquitin binding. His224 and Asn226 form a stable hydrogen bond in OTUB2. The active site is more solvent-accessible in OTUB2 than in OTUB1. Molecular dynamics simulations (computational; Tier 4) The Journal of biological chemistry Low 32265297
2022 OTUB2 promotes deubiquitination and phosphorylation of STAT1, subsequently regulating CALML3 transcription. CALML3-mediated mitochondrial calcium signaling promotes oxidative phosphorylation and phosphatidylserine synthesis, and this OTUB2/STAT1/CALML3/PS axis exerts tumor-suppressive roles in tongue and esophageal SCC. Co-immunoprecipitation, ubiquitination assays, phosphorylation assays, transcriptional reporter assays, mouse models with orally administered phosphatidylserine Cell reports Medium 36288705
2024 OTUB2 silencing in ovarian cancer destabilizes SNX29P2, which prevents HIF-1α from VHL-mediated degradation. Elevated HIF-1α then activates CA9 transcription, driving glycolysis, tumor progression, and chemoresistance. Genetic silencing of OTUB2, protein stability assays, HIF-1α/VHL interaction assays, CA9 transcriptional reporter, pharmacological CA9 inhibition with carboplatin synergy in vivo Proceedings of the National Academy of Sciences of the United States of America Medium 38701117
2022 OTUB2 stabilizes KRT80 by removing K48- and K63-linked ubiquitin chains, protecting it from proteasomal degradation. OTUB2 and KRT80 together activate AKT signaling to promote gastric cancer cell proliferation. Co-immunoprecipitation, ubiquitination assays specifying K48 and K63 linkages, knockdown/rescue experiments, in vivo xenograft Cell death discovery Medium 35110531
2022 OTUB2 binds to β-Catenin, deubiquitinates it (catalytically inactive OTUB2 fails to do so), stabilizes it, and enhances β-Catenin/TCF-mediated transcription including CCND1 and MYC in colorectal cancer cells. LC-MS/MS interactomics, reciprocal Co-immunoprecipitation, ubiquitination assays with catalytic mutant, cycloheximide chase, TCF-luciferase reporter American journal of cancer research Medium 38058843
2022 OTUB2 promotes CTNNB1 (β-Catenin) stability by interacting with E3 ligase TRAF6 and inhibiting lysosomal degradation of CTNNB1, which then upregulates ZEB1 to drive EMT and metastasis in intrahepatic cholangiocarcinoma. Co-immunoprecipitation, ubiquitination assays, lysosomal inhibitor experiments, knockdown/overexpression with EMT markers Experimental cell research Medium 36858343
2025 OTUB2 removes K48-linked polyubiquitin chains from RIPK3 via its active-site residue C51, inhibiting proteasomal degradation of RIPK3 and potentiating RIPK3-mediated neuronal necroptosis after ischemic stroke. Genetic deletion or pharmacological inhibition of OTUB2 reduced infarction and neurological deficits. OTUB2 knockout mice, active-site mutant (C51) analysis, K48-linkage-specific ubiquitination assays, pharmacological inhibitor in mouse stroke model and human brain organoids EMBO molecular medicine High 40021931
2024 OTUB2 deubiquitinates RIPK2, removing K48-linked polyubiquitin chains via its C51 active-site residue, thereby inhibiting proteasomal degradation of RIPK2 and promoting NOD2 signaling in macrophages. OTUB2-deficient mice show impaired cytokine/chemokine production in response to NOD2 agonist MDP and exacerbated colitis. Otub2 knockout mice, bone marrow transplantation, Co-IP, K48-specific ubiquitination assays, active-site mutant C51, cytokine assays Clinical and translational medicine High 39358938
2025 OTUB2 binds YAP and removes its K48-linked polyubiquitin chains, inhibiting YAP proteasomal degradation, thereby activating YAP-PFKFB3 transcriptional signaling and promoting vascular smooth muscle cell calcification in CKD. The YAP/TEAD1 complex binds the PFKFB3 promoter (confirmed by CUT&RUN-qPCR). Co-immunoprecipitation, K48-specific ubiquitination assays, AAV9-mediated VSMC-specific OTUB2 KO/overexpression in mice, CUT&RUN-qPCR, Von Kossa/Alizarin red staining Theranostics Medium 39776804
2021 OTUB2 promotes gastric cancer stemness by deubiquitinating and stabilizing KDM1A (LSD1), a histone demethylase. KDM1A overexpression reversed the effects of OTUB2 knockdown on stem cell markers and tumorigenicity. (NOTE: The original paper PMID:34646768 was retracted per PMID:37287909.) Co-immunoprecipitation, ubiquitination assays, sphere-formation assays, in vivo xenograft (RETRACTED) Frontiers in oncology Low 34646768
2025 OTUB2 stabilizes TRAF6 by deubiquitinating it, leading to AKT pathway activation and promotion of TNBC cell proliferation and migration. Co-immunoprecipitation, ubiquitination assays, Western blotting, knockdown/overexpression functional assays Oncology research Low 40296903
2022 OTUB2 acts as a deubiquitinase for SP1 protein, binding SP1 and inhibiting its K48-linked ubiquitination, thereby stabilizing SP1. SP1 then acts as a transcription factor for GINS1 (binding the 1822–1830 region of the GINS1 promoter), upregulating GINS1 to drive stemness, chemoresistance, and EMT in colon cancer. Co-immunoprecipitation, K48-specific ubiquitination assays, ChIP-qPCR, dual luciferase reporter, sphere-formation assays Cell communication and signaling Medium 39210373
2022 OTUB2 deubiquitinates and stabilizes PJA1 (an E3 ubiquitin ligase) in hepatocellular carcinoma cells, as shown by Co-IP and cycloheximide chase assays, and this stabilization promotes malignant proliferation and migration. Co-immunoprecipitation, cycloheximide chase, ubiquitination assays, knockdown/rescue experiments Cellular and molecular bioengineering Low 35611163
2018 OTUB2 acts as a direct downstream target of miR-29a-3p in papillary thyroid carcinoma. OTUB2 overexpression activates NF-κB signaling predominantly by stabilizing TRAF6 (confirmed by Western blot and luciferase reporter). Luciferase reporter assay for miR-29a-3p targeting of OTUB2, Western blot for TRAF6 stabilization, NF-κB reporter Cancer management and research Low 30588107
2025 OTUB2 interacts with UBE2S (ubiquitin-conjugating enzyme E2S) and PGAM1; this complex inhibits K48-linked polyubiquitination-mediated degradation of PGAM1, increasing PGAM1 levels and promoting DNA repair, thereby reducing sensitivity of glioblastoma cells to temozolomide. Co-immunoprecipitation with mass spectrometry, ubiquitination assays (K48-linked), knockdown functional assays, in vivo GBM mouse model International journal of biological macromolecules Medium 39904430
2025 OTUB2 deubiquitinates NR4A1, suppressing its proteasomal degradation, with the C51 residue being essential for OTUB2 catalytic activity. This stabilization of NR4A1 suppresses macrophage M1 polarization and experimental preeclampsia in rodents. Co-immunoprecipitation, ubiquitination assays, OTUB2 C51 active-site mutant, gain/loss-of-function in macrophages, LPS-induced rat preeclampsia model Communications biology Medium 40883596
2026 OTUB2 stabilizes ALYREF (m5C reader) by removing K48-linked polyubiquitin chains, leading to increased ALYREF that enhances ABCG4 mRNA stability and expression, promoting ATP-dependent efflux of docetaxel in castration-resistant prostate cancer. Co-immunoprecipitation, K48-specific ubiquitination assays, mRNA stability assays, OTUB2 inhibitor (OTUB2-IN-1) treatment International journal of biological sciences Low 42003916
2026 OTUB2 binds and deubiquitinates HASPIN kinase, counteracting K48-linked polyubiquitination and proteasomal degradation of HASPIN. KAT5-mediated acetylation of HASPIN at K751 enhances HASPIN's affinity for OTUB2, further promoting HASPIN stability and breast cancer cell proliferation/invasion. Co-immunoprecipitation, K48-specific ubiquitination assays, acetylation assays, OTUB2 knockdown/overexpression, in vivo xenograft Cell death & disease Medium 41896530
2026 OTUB2 deubiquitinates and stabilizes EIF4A3; EIF4A3 in turn interacts with TPI1 to stabilize its mRNA, promoting glycolysis and TNBC progression. Co-immunoprecipitation, ubiquitination assays, mRNA stability assays, knockdown/overexpression functional assays, in vivo xenograft Breast cancer research Low 41857621
2026 OTUB2 deubiquitinates YAP and TAZ in gastric cancer cells, preventing their degradation, and activates TGF-β1/SMAD signaling (by inhibiting SMAD7) to promote M2 tumor-associated macrophage polarization. OTUB2 also stabilizes PD-L1 (CD274) via deubiquitination, enhancing immune evasion. Co-immunoprecipitation, Western blotting, ubiquitination assays, flow cytometry (M2 TAMs, CD274), T cell killing assays, in vivo tumor models Cell death & disease Medium 41986305
2026 OTUB2 interacts with voltage-gated potassium channel subunit Kv9.3, Peg3, and Camk2d in pancreatic β-cells (identified by Co-IP/mass spectrometry). OTUB2 inhibits NF-κB activity and enhances glucose-stimulated insulin secretion; OTUB2 KO mice exhibit impaired glucose tolerance and downregulation of K+ transporter genes. Co-immunoprecipitation with mass spectrometry, RNA sequencing of KO pancreata, glucose tolerance tests, MIN6 cell overexpression/silencing, AAV9-mediated overexpression in mouse pancreata Frontiers in bioscience Medium 41914276
2025 OTUB2 upregulates total and GTP-bound (active) Rac1 and activates the downstream MEK/ERK pathway, promoting pathological cardiac hypertrophy. Pharmacological inhibition of Rac1 with NSC23766 abolished OTUB2-mediated hypertrophic responses. AAV9-mediated cardiomyocyte-specific overexpression, TAC mouse model, Rac1 activity assay (GTP-bound Rac1 pulldown), pharmacological Rac1 inhibition, neonatal rat cardiomyocyte knockdown/overexpression Human cell Medium 41329260

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 OTUB2 Promotes Cancer Metastasis via Hippo-Independent Activation of YAP and TAZ. Molecular cell 166 30472188
2009 Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. The Journal of biological chemistry 161 19996094
2019 OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer. Theranostics 128 30662561
2021 Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. Oncogene 89 34671086
2014 Fine-tuning of DNA damage-dependent ubiquitination by OTUB2 supports the DNA repair pathway choice. Molecular cell 86 24560272
2024 Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1. Nature communications 52 38167274
2018 miR-29a-3p inhibits growth, proliferation, and invasion of papillary thyroid carcinoma by suppressing NF-κB signaling via direct targeting of OTUB2. Cancer management and research 46 30588107
2022 OTUB2 exerts tumor-suppressive roles via STAT1-mediated CALML3 activation and increased phosphatidylserine synthesis. Cell reports 39 36288705
2023 RBM15 m6 A modification-mediated OTUB2 upregulation promotes cervical cancer progression via the AKT/mTOR signaling. Environmental toxicology 29 37334762
2022 OTUB2 regulates KRT80 stability via deubiquitination and promotes tumour proliferation in gastric cancer. Cell death discovery 26 35110531
2024 OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition. Proceedings of the National Academy of Sciences of the United States of America 25 38701117
2020 Activation and selectivity of OTUB-1 and OTUB-2 deubiquitinylases. The Journal of biological chemistry 25 32265297
2018 Regulation of Gli2 stability by deubiquitinase OTUB2. Biochemical and biophysical research communications 16 30241937
2025 Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke. EMBO molecular medicine 15 40021931
2024 Honokiol induces ferroptosis in ovarian cancer cells through the regulation of YAP by OTUB2. The journal of obstetrics and gynaecology research 14 38480480
2022 OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma. Biological procedures online 12 35850645
2022 OTUB2 promotes the progression of endometrial cancer by regulating the PKM2-mediated PI3K/AKT signaling pathway. Cell biology international 12 36316812
2020 OTUB2 Promotes Homologous Recombination Repair Through Stimulating Rad51 Expression in Endometrial Cancer. Cell transplantation 11 32830515
2022 OTUB2 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by PJA1 Deubiquitylation. Cellular and molecular bioengineering 9 35611163
2025 OTUB2 contributes to vascular calcification in chronic kidney disease via the YAP-mediated transcription of PFKFB3. Theranostics 8 39776804
2024 OTU deubiquitinase, ubiquitin aldehyde binding 2  (OTUB2) modulates the stemness feature, chemoresistance, and epithelial-mesenchymal transition of colon cancer via regulating GINS complex subunit 1 (GINS1) expression. Cell communication and signaling : CCS 8 39210373
2023 Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating β-Catenin signaling. American journal of cancer research 8 38058843
2021 OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties. Frontiers in oncology 8 34646768
2022 The Emerging Role of OTUB2 in Diseases: From Cell Signaling Pathway to Physiological Function. Frontiers in cell and developmental biology 7 35309903
2024 Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation. Clinical and translational medicine 6 39358938
2023 Deubiquitinase OTUB2 promotes intrahepatic cholangiocarcinoma progression by stabilizing the CTNNB1-ZEB1 axis. Experimental cell research 6 36858343
2025 Ubiquitin-conjugating enzyme E2S decreases the sensitivity of glioblastoma cells to temozolomide by upregulating PGAM1 via the interaction with OTUB2. International journal of biological macromolecules 5 39904430
2025 OTUB2 promotes proliferation and metastasis of triple-negative breast cancer by deubiquitinating TRAF6. Oncology research 5 40296903
2024 Exploring the regulatory role of FBXL19-AS1 in triple-negative breast cancer through the miR-378a-3p/OTUB2 axis. Cell biochemistry and function 3 38702967
2024 circRNA6448-14/miR-455-3p/OTUB2 axis stimulates glycolysis and stemness of esophageal squamous cell carcinoma. Aging 3 38819228
2024 The deubiquitinase OTUB2 promotes cervical cancer growth through stabilizing FOXM1. American journal of translational research 2 38322554
2024 Grouper OTUB1 and OTUB2 promote red-spotted grouper nervous necrosis virus (RGNNV) replication by inhibiting the host innate immune response. Fish & shellfish immunology 2 38909637
2025 OTUB2/NR4A1 restrains the development of preeclampsia by suppressing macrophage M1 polarization. Communications biology 1 40883596
2026 Deubiquitination and stabilization of EIF4A3 by OTUB2 contributes to TPI1-mediated glycolysis and TNBC progression. Breast cancer research : BCR 0 41857621
2026 KAT5-mediated acetylation enhances the deubiquitination of HASPIN by OTUB2 and promotes breast cancer progression. Cell death & disease 0 41896530
2026 The Deubiquitinating Enzyme Otub2 Modulates Pancreatic Beta-Cells Function and Survival. Frontiers in bioscience (Landmark edition) 0 41914276
2026 OTUB2 Mutation Promotes Thyroid Collision Tumor's Insights From the Whole-exome Sequence. Frontiers in bioscience (Landmark edition) 0 41914283
2026 OTUB2 induces M2 tumor-associated macrophage polarization and increases CD274 expression in gastric cancer cells to aggravate the progression of gastric cancer. Cell death & disease 0 41986305
2026 OTUB2/ALYREF axis modulates the docetaxel resistance of castration-resistant prostate cancer via upregulating ABCG4-mediated drug efflux. International journal of biological sciences 0 42003916
2026 OTUB2-mediated deubiquitination upregulates U2AF2 to promote colorectal cancer evasion of autophagy-ferroptosis. Cell death & disease 0 42098079
2026 Cancer-associated fibroblasts-derived exosomal circ_0067557 promotes colorectal cancer epithelial-mesenchymal transition via BHLHE40-mediated transcriptional activation of OTUB2. Biology direct 0 42115880
2025 OTUB2 aggravates pathological cardiac hypertrophy through Rac1 activation. Human cell 0 41329260
2023 Retraction: OTUB2 facilitates tumorigenesis of gastric cancer through promoting KDM1A-mediated stem cell-like properties. Frontiers in oncology 0 37287909

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