Affinage

OTUB2

Ubiquitin thioesterase OTUB2 · UniProt Q96DC9

Length
234 aa
Mass
27.2 kDa
Annotated
2026-04-29
40 papers in source corpus 27 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTUB2 is an OTU-family cysteine deubiquitinase (catalytic residue C51) that removes primarily K48-linked and, in some contexts, K63-linked polyubiquitin chains from a broad array of substrates, thereby preventing their proteasomal degradation and modulating diverse signaling pathways including innate immunity, DNA damage repair, Hippo/YAP-TAZ, Wnt/β-catenin, Hedgehog, NF-κB, and necroptosis (PMID:19996094, PMID:24560272, PMID:30472188, PMID:40021931, PMID:39358938). Its substrate repertoire includes TRAF3/TRAF6 (regulating type I IFN and NF-κB signaling), YAP/TAZ (activated via EGF/KRAS-induced poly-SUMOylation of OTUB2 at K233), PD-L1 (stabilized in the endoplasmic reticulum to promote immune evasion), RIPK2 (augmenting NOD2-dependent intestinal immunity), RIPK3 (potentiating neuronal necroptosis), β-catenin, PKM2, and Gli2, among others (PMID:30472188, PMID:38167274, PMID:39358938, PMID:40021931, PMID:38058843, PMID:34671086, PMID:30241937). At DNA double-strand breaks, OTUB2 counteracts RNF8-dependent ubiquitination to limit 53BP1/RAP80 accumulation and bias repair toward homologous recombination (PMID:24560272). In pancreatic beta cells, OTUB2 suppresses NF-κB activity and is required for normal glucose-stimulated insulin secretion, with Otub2 knockout mice displaying impaired glucose tolerance (PMID:41914276).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2009 High

    The first functional characterization established OTUB2 as a negative regulator of innate antiviral signaling, answering whether OTU-family DUBs beyond OTUB1 participate in immune regulation by showing that OTUB2 deubiquitinates TRAF3 and TRAF6 to suppress IRF3/NF-κB activation and type I IFN induction.

    Evidence Co-immunoprecipitation of OTUB2 with TRAF3/TRAF6, overexpression/knockdown with IFN-β and NF-κB reporter assays in HEK293 cells

    PMID:19996094

    Open questions at the time
    • Ubiquitin chain-linkage specificity on TRAF3/TRAF6 not determined
    • In vivo role in antiviral defense not tested with KO mice
    • Mechanism of OTUB2 recruitment to TRAF substrates unknown
  2. 2014 High

    Extending OTUB2 function beyond immune signaling, this work showed that OTUB2 operates at DNA double-strand breaks to suppress RNF8-mediated K63-linked ubiquitination and L3MBTL1 ubiquitination, thereby limiting 53BP1/RAP80 accumulation and favoring homologous recombination over NHEJ.

    Evidence siRNA depletion, ubiquitination assays, DDR foci quantification, epistasis with RNF8, catalytic-dead mutant rescue in U2OS cells

    PMID:24560272

    Open questions at the time
    • How OTUB2 is recruited to DSBs is unknown
    • No in vivo validation of HR bias
    • Relative contributions of OTUB2 versus other DUBs at DSBs not quantified
  3. 2018 High

    A key regulatory mechanism was uncovered: poly-SUMOylation of OTUB2 at K233 (induced by EGF/oncogenic KRAS) enables OTUB2 to bind YAP/TAZ through a SUMO-interacting motif, establishing a Hippo-independent route to YAP/TAZ activation via deubiquitination — linking OTUB2 to oncogenic transcription programs.

    Evidence Gain-of-function screen, SUMOylation mapping, K233 mutagenesis, SIM identification, deubiquitination assay, and Co-IP with Gli2 in parallel study

    PMID:30241937 PMID:30472188

    Open questions at the time
    • Structural basis of SUMOylated OTUB2–YAP SIM interaction unresolved
    • Identity of the E3 SUMO ligase for OTUB2 unknown
    • Whether SUMOylation also regulates other substrate interactions not tested
  4. 2019 High

    OTUB2's role in cancer metabolism emerged through its stabilization of the splicing factor U2AF2, which promotes the Warburg effect and AKT/mTOR signaling in NSCLC, demonstrating that OTUB2 substrates extend to RNA-binding proteins with metabolic consequences.

    Evidence Co-IP/mass spectrometry, ubiquitination assay, knockdown/overexpression in NSCLC cells, xenograft model

    PMID:30662561

    Open questions at the time
    • Which E3 ligase ubiquitinates U2AF2 not identified
    • Specific ubiquitin chain linkage on U2AF2 not determined
    • Whether OTUB2 regulation of U2AF2 affects splicing globally is unknown
  5. 2020 Low

    Molecular dynamics simulations provided a model for OTUB2's catalytic mechanism, revealing that its catalytic triad (Cys-His-Asn/Asp) rearranges into a competent state only upon ubiquitin binding, contrasting with the pre-organized active site of OTUB1.

    Evidence Molecular dynamics simulation, protonation state and water channel analysis of OTUB2 crystal structure

    PMID:32265297

    Open questions at the time
    • Computational prediction only; no experimental validation of substrate-induced catalytic rearrangement
    • No mutational testing of predicted catalytic triad residues in this study
    • Structural basis for substrate selectivity not addressed
  6. 2021 High

    OTUB2 was shown to stabilize PKM2 not only by removing K48/K63-linked ubiquitin chains but also by blocking Parkin (the E3 ligase) from accessing PKM2, revealing a dual mechanism — deubiquitination plus E3 occlusion — that promotes aerobic glycolysis in colorectal cancer.

    Evidence Co-IP, ubiquitination assay, CRISPR knockout, metabolic assays, in vivo tumor model in CRC cells

    PMID:34671086

    Open questions at the time
    • Structural basis for Parkin competition not determined
    • Whether E3 occlusion is a general OTUB2 mechanism or substrate-specific is unknown
  7. 2022 High

    Multiple studies converged to demonstrate that OTUB2 stabilizes diverse oncogenic and signaling substrates — β-catenin (activating Wnt/TCF transcription), STAT1 (driving CALML3 expression), KRT80 (activating Akt), and PJA1 — in distinct cancer types, cementing OTUB2 as a pleiotropic oncogenic DUB.

    Evidence Reciprocal Co-IP with catalytic mutant, CHX chase, TCF-luciferase reporter for β-catenin; STAT1 phosphorylation/ubiquitination assays; KRT80 and PJA1 Co-IP and ubiquitination assays in multiple cancer cell lines with in vivo models

    PMID:35110531 PMID:35611163 PMID:36288705 PMID:38058843

    Open questions at the time
    • Whether OTUB2 shows substrate hierarchy or context-dependent selectivity is unexplored
    • Upstream signals regulating OTUB2 expression in these cancer contexts are largely unknown
    • No structural basis for multi-substrate recognition
  8. 2024 High

    Studies using knockout mice and pharmacological inhibitors established two critical in vivo roles for OTUB2: stabilizing PD-L1 in the ER to promote tumor immune evasion, and stabilizing RIPK3 to potentiate neuronal necroptosis after ischemic stroke — both validated with OTUB2-specific inhibitors, opening therapeutic avenues.

    Evidence Genetic deletion, flow cytometry for surface PD-L1, CD8+ T cell killing assay, OTUB2 inhibitor in xenografts; conditional KO mouse, C51 mutant, ubiquitination assay, OTUB2 inhibitor in stroke model and human brain organoids

    PMID:38167274 PMID:40021931

    Open questions at the time
    • Selectivity and off-target profile of OTUB2 inhibitors not fully characterized
    • PD-L1 stabilization mechanism in the ER versus plasma membrane not fully dissected
    • Whether OTUB2 inhibition affects other necroptosis components beyond RIPK3 is unknown
  9. 2024 High

    Otub2 knockout mice revealed a protective role in intestinal immunity: OTUB2 stabilizes RIPK2 via K48-linked deubiquitination to augment NOD2 signaling in macrophages, and its loss aggravates experimental colitis — establishing a physiological immune-regulatory function beyond cancer.

    Evidence Otub2−/− mice, bone marrow transplantation chimeras, C51 mutant, ubiquitination assay, DSS colitis model

    PMID:39358938

    Open questions at the time
    • Human genetic variation in OTUB2 linked to IBD susceptibility not investigated
    • Whether OTUB2 regulates other NOD-like receptor pathways is unknown
  10. 2025 Medium

    OTUB2's substrate repertoire expanded further to include SP1 (promoting GINS1-driven stemness in colon cancer), ALYREF (promoting drug efflux and docetaxel resistance), NR4A1 (restraining macrophage M1 polarization in preeclampsia), and activation of Rac1/MEK/ERK in cardiac hypertrophy — reinforcing its role as a broadly acting stabilizing DUB with context-dependent physiological and pathological outputs.

    Evidence Co-IP, ubiquitination assays, ChIP-qPCR, AAV9-mediated cardiac overexpression with TAC model, Rac1 GTP-pulldown, active-site mutant validation

    PMID:39210373 PMID:40883596 PMID:41329260 PMID:42003916

    Open questions at the time
    • Rac1 may be an indirect target — direct deubiquitination not demonstrated
    • Whether OTUB2 deubiquitinates ALYREF directly at specific lysines needs mapping
    • Cardiac-specific substrates of OTUB2 beyond Rac1 pathway unidentified
  11. 2026 Medium

    Recent work established OTUB2 in pancreatic beta-cell function (KO mice show impaired glucose tolerance and elevated NF-κB) and confirmed OTUB2 as a dual stabilizer of YAP/TAZ and PD-L1 in gastric cancer driving immune evasion via TGF-β1/M2 macrophage polarization, while HASPIN stabilization via acetylation-enhanced OTUB2 binding revealed a post-translational code governing substrate access.

    Evidence Otub2 KO mice with GSIS and RNA-seq; Co-IP/ubiquitination/flow cytometry/T cell assays in gastric cancer; KAT5 acetylation at K751 mutagenesis enhancing HASPIN–OTUB2 binding with in vivo xenograft

    PMID:41896530 PMID:41914276 PMID:41986305

    Open questions at the time
    • Beta-cell substrates (Peg3, Camk2d) identified by MS need biochemical confirmation of direct deubiquitination
    • Whether acetylation-dependent substrate recruitment is a general mechanism for other OTUB2 substrates is unknown
    • Structural basis for how SUMOylation and acetylation codes converge on OTUB2 substrate selection unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for OTUB2's remarkably broad substrate selectivity, the upstream signaling pathways controlling OTUB2 expression and post-translational modifications (SUMOylation, potentially others), the therapeutic window of OTUB2 inhibitors given its roles in both protective immunity and pathological necroptosis/cancer, and whether OTUB2 has non-catalytic scaffolding functions analogous to OTUB1.
  • No crystal structure of OTUB2 bound to any substrate exists
  • No systematic analysis of OTUB2 chain-linkage preference using defined di-ubiquitin panels
  • Non-catalytic functions (if any) have not been systematically tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 10 GO:0140096 catalytic activity, acting on a protein 10
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-392499 Metabolism of proteins 8 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 1 R-HSA-73894 DNA Repair 1
Partners
CTNNB1PKMRIPK2RIPK3TRAF3TRAF6WWTR1YAP1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 OTUB2 interacts with TRAF3 and TRAF6 (by co-immunoprecipitation) and mediates their deubiquitination, thereby negatively regulating virus-triggered type I IFN induction and NF-κB activation. Overexpression inhibited IRF3/NF-κB activation and IFNB1 transcription; knockdown had opposite effects. Co-immunoprecipitation, overexpression/knockdown with reporter assays The Journal of biological chemistry High 19996094
2014 OTUB2 suppresses RNF8-mediated ubiquitination (including K63-linked ubiquitin chain formation and L3MBTL1 ubiquitination) at DNA double-strand breaks in a deubiquitinating-activity-dependent manner, thereby fine-tuning the speed of DSB-induced ubiquitination and biasing repair pathway choice toward homologous recombination by limiting 53BP1 and RAP80 accumulation and DSB end protection. siRNA depletion, ubiquitination assays, DDR factor accumulation (foci), epistasis with RNF8, deubiquitinase activity-dependent rescue Molecular cell High 24560272
2018 OTUB2 is poly-SUMOylated on lysine 233, and this SUMOylation enables it to bind YAP and TAZ via a novel SUMO-interacting motif (SIM) in YAP/TAZ. OTUB2 deubiquitinates YAP/TAZ to activate them independently of the Hippo pathway. EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation to activate YAP/TAZ. Gain-of-function screen, Co-IP, SUMOylation mapping, mutagenesis of K233, SIM identification, deubiquitination assay Molecular cell High 30472188
2019 OTUB2 directly binds to and deubiquitinates U2AF2, stabilizing it from proteasomal degradation. This stabilization promotes the Warburg effect and activates the AKT/mTOR pathway in non-small cell lung cancer cells. Co-immunoprecipitation, mass spectrometry, ubiquitination assay, knockdown/overexpression with functional assays, xenograft model Theranostics High 30662561
2018 OTUB2 co-immunoprecipitates with Gli2 and deubiquitinates it (confirmed by in vitro deubiquitination assay with catalytic mutant OTUB2 failing to rescue), thereby stabilizing Gli2 and extending its half-life, promoting Hedgehog signaling and osteogenic differentiation of MSCs. Co-immunoprecipitation, in vitro deubiquitination assay, active-site mutagenesis, cycloheximide chase, knockdown with proteasome inhibitor rescue Biochemical and biophysical research communications High 30241937
2021 OTUB2 directly interacts with PKM2 and inhibits its K48/K63-linked ubiquitination by blocking interaction between PKM2 and its E3 ligase Parkin, thereby enhancing PKM2 activity and promoting aerobic glycolysis in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assay, OTUB2 knockout (CRISPR), in vivo tumor model, metabolic assays Oncogene High 34671086
2024 OTUB2 directly interacts with PD-L1 in the endoplasmic reticulum to disrupt its ubiquitination and proteasomal degradation, stabilizing PD-L1 on the tumor cell surface and promoting immune evasion. An OTUB2 inhibitor targeting its deubiquitinase activity (without disrupting the OTUB2-PD-L1 interaction) reduces PD-L1 expression and suppresses tumor growth. Co-IP, genetic deletion, flow cytometry for surface PD-L1, CD8+ T cell killing assay, pharmacological inhibitor, xenograft model Nature communications High 38167274
2022 OTUB2 promotes deubiquitination and phosphorylation of STAT1, which then drives transcription of CALML3. CALML3-mediated mitochondrial calcium signaling promotes oxidative phosphorylation and phosphatidylserine synthesis, acting as a tumor suppressor axis in squamous cell carcinomas. OTUB2 depletion/overexpression, ubiquitination and phosphorylation assays, transcriptional reporter, metabolic assays, mouse models Cell reports Medium 36288705
2022 OTUB2 stabilizes KRT80 by deubiquitinating it (removing K48- and K63-linked chains) and protecting it from proteasomal degradation, thereby activating the Akt signaling pathway to promote gastric cancer cell proliferation. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, in vivo xenograft, rescue with KRT80 re-expression Cell death discovery Medium 35110531
2022 OTUB2 binds to and deubiquitinates β-Catenin in a catalytic-activity-dependent manner (catalytic-inactive mutant failed to reduce ubiquitination), increasing β-Catenin half-life, nuclear levels, and TCF-mediated transcription of CCND1 and MYC in colorectal cancer cells. Co-immunoprecipitation, LC-MS/MS, reciprocal Co-IP, ubiquitination assay with catalytic mutant, cycloheximide chase, TCF-luciferase reporter American journal of cancer research High 38058843
2022 OTUB2 deubiquitinates KDM1A to increase its stability, promoting cancer stem cell-like properties and gastric cancer tumorigenesis. (Note: PMID 34646768 was subsequently retracted per PMID 37287909.) Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression with sphere formation and rescue experiments Frontiers in oncology Low 34646768 37287909
2022 OTUB2 promotes CTNNB1 (β-catenin) stability in intrahepatic cholangiocarcinoma by interacting with the E3 ligase TRAF6, inhibiting lysosomal degradation of CTNNB1, which in turn regulates ZEB1 expression and drives EMT and metastasis. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, in vivo model Experimental cell research Medium 36858343
2023 OTUB2 binds SP1 protein and inhibits its K48-linked ubiquitination, stabilizing SP1. Stabilized SP1 binds the GINS1 promoter (region 1822–1830) to enhance its transcription, driving stemness, chemoresistance, and EMT in colon cancer. Co-immunoprecipitation, ubiquitination assay, ChIP-qPCR, dual-luciferase reporter, knockdown/overexpression Cell communication and signaling Medium 39210373
2024 OTUB2 removes K48-linked polyubiquitin chains from RIPK3 via its active site C51, inhibiting proteasomal degradation of RIPK3 and thereby potentiating neuronal necroptosis after ischemic stroke. Pharmacological inhibition of OTUB2 reduced ischemic brain injury in mice and neuronal death in human brain organoids. Conditional KO mouse (OTUB2 deletion), active-site mutant (C51), ubiquitination assay, pharmacological inhibitor, human brain organoid model, in vivo stroke model EMBO molecular medicine High 40021931
2024 OTUB2 removes K48-linked polyubiquitination from RIPK2 via its active site C51, stabilizing RIPK2 and augmenting NOD2 signaling in macrophages, thereby providing protective effects in intestinal inflammation. Otub2-/- mice showed aggravated DSS-induced colitis and impaired MDP-stimulated cytokine production. Otub2-/- mice, bone marrow transplantation, biochemical ubiquitination assay, active-site mutant (C51), DSS colitis model Clinical and translational medicine High 39358938
2024 OTUB2 silencing in ovarian cancer destabilizes SNX29P2, preventing VHL-mediated degradation of HIF-1α, which then activates CA9 transcription to drive glycolysis and chemoresistance. Epigenetic silencing analysis, protein stability assays, knockdown/overexpression, pharmacological CA9 inhibitor, xenograft model Proceedings of the National Academy of Sciences of the United States of America Medium 38701117
2020 Molecular dynamics simulations revealed that OTUB2 has a catalytic triad (cysteine, histidine, asparagine/aspartate) that only rearranges into a catalytically competent state upon ubiquitin binding, differing from OTUB1's pre-arranged active site. His224 and Asn226 in OTUB2 form a stable hydrogen bond, and the active site is more solvent-accessible than OTUB1. Molecular dynamics simulation, protonation state analysis, water channel analysis The Journal of biological chemistry Low 32265297
2022 OTUB2 stabilizes PJA1 by deubiquitylation (shown by Co-IP and cycloheximide assay), increasing PJA1 protein stability and thereby promoting proliferation and metastasis of hepatocellular carcinoma cells. Co-immunoprecipitation, cycloheximide chase, ubiquitination assay, knockdown/overexpression Cellular and molecular bioengineering Medium 35611163
2024 OTUB2 binds to YAP and removes its K48-linked polyubiquitination, inhibiting proteasomal degradation of YAP, in vascular smooth muscle cells. OTUB2-stabilized YAP forms a complex with TEAD1 to transcriptionally activate PFKFB3, promoting vascular calcification in chronic kidney disease. Co-IP, ubiquitination assay, VSMC-specific KO/overexpression via AAV9, CUT&RUN-qPCR for YAP/TEAD1 binding to PFKFB3 promoter, in vivo CKD mouse model Theranostics High 39776804
2025 OTUB2 stabilizes the m5C-reader ALYREF by removing its K48-linked polyubiquitin chains. ALYREF then enhances ABCG4 mRNA stability and expression, promoting ATP-dependent drug efflux and docetaxel resistance in castration-resistant prostate cancer. Co-IP, ubiquitination assay, knockdown/overexpression, mRNA stability assay, OTUB2 inhibitor (OTUB2-IN-1), xenograft model International journal of biological sciences Medium 42003916
2025 OTUB2 promotes macrophage M1 polarization suppression and protects trophoblast function by deubiquitinating NR4A1 (active site C51 required), stabilizing it from degradation, and thereby restraining preeclampsia progression. Gain/loss-of-function in macrophages, active-site mutant (C51), ubiquitination assay, LPS-induced rat preeclampsia model, trophoblast invasion/migration assays Communications biology Medium 40883596
2025 OTUB2 interacts with and deubiquitinates TRAF6, stabilizing it and activating the TRAF6/AKT pathway to promote proliferation and migration in triple-negative breast cancer. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression with functional assays Oncology research Medium 40296903
2025 OTUB2 upregulates both total and GTP-bound active Rac1 in cardiomyocytes, activating the downstream MEK/ERK pathway. Cardiomyocyte-specific OTUB2 overexpression (AAV9) exacerbated TAC-induced cardiac hypertrophy and remodeling; pharmacological Rac1 inhibition abolished OTUB2-mediated hypertrophic responses. AAV9-mediated cardiomyocyte-specific overexpression, TAC mouse model, Rac1 GTP-pulldown assay, Rac1 pharmacological inhibition (NSC23766), knockdown in NRCMs Human cell Medium 41329260
2026 OTUB2 binds and deubiquitinates HASPIN (counteracting K48-linked polyubiquitination), preventing its proteasomal degradation. KAT5-mediated acetylation of HASPIN at K751 enhances its affinity for OTUB2, further promoting HASPIN stability and breast cancer proliferation/invasion. Co-IP, ubiquitination assay, OTUB2 knockdown/overexpression, KAT5 acetyltransferase assay, K751 acetylation mutagenesis, in vivo xenograft Cell death & disease Medium 41896530
2026 In pancreatic beta cells, OTUB2 inhibits NF-κB activity and enhances glucose-stimulated insulin secretion. Otub2 KO mice show impaired glucose tolerance and upregulation of NF-κB target genes. Mass spectrometry identified voltage-gated potassium channel subunit Kv9.3, Peg3, and Camk2d as OTUB2 binding partners, suggesting OTUB2 deubiquitinates Peg3 and Camk2d to protect beta cells from cytokine-induced apoptosis. Co-IP/mass spectrometry, Otub2 KO mice, pancreas-specific overexpression, RNA sequencing, glucose tolerance test, GSIS assay Frontiers in bioscience (Landmark edition) Medium 41914276
2026 OTUB2 deubiquitinates both YAP and TAZ (and also PD-L1/CD274) in gastric cancer cells, preventing their degradation. OTUB2-stabilized YAP/TAZ activate TGF-β1 expression (inhibiting SMAD7) to promote M2 tumor-associated macrophage polarization and immune evasion. Co-IP, ubiquitination assay, OTUB2 knockdown/overexpression, flow cytometry, T cell killing assay, in vivo mouse model, IHC of GC tissues Cell death & disease Medium 41986305

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. The Journal of biological chemistry 160 19996094
2018 OTUB2 Promotes Cancer Metastasis via Hippo-Independent Activation of YAP and TAZ. Molecular cell 159 30472188
2019 OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer. Theranostics 123 30662561
2014 Fine-tuning of DNA damage-dependent ubiquitination by OTUB2 supports the DNA repair pathway choice. Molecular cell 85 24560272
2021 Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. Oncogene 84 34671086
2024 Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1. Nature communications 49 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 45 30588107
2022 OTUB2 exerts tumor-suppressive roles via STAT1-mediated CALML3 activation and increased phosphatidylserine synthesis. Cell reports 38 36288705
2023 RBM15 m6 A modification-mediated OTUB2 upregulation promotes cervical cancer progression via the AKT/mTOR signaling. Environmental toxicology 27 37334762
2020 Activation and selectivity of OTUB-1 and OTUB-2 deubiquitinylases. The Journal of biological chemistry 25 32265297
2022 OTUB2 regulates KRT80 stability via deubiquitination and promotes tumour proliferation in gastric cancer. Cell death discovery 24 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 23 38701117
2018 Regulation of Gli2 stability by deubiquitinase OTUB2. Biochemical and biophysical research communications 16 30241937
2024 Honokiol induces ferroptosis in ovarian cancer cells through the regulation of YAP by OTUB2. The journal of obstetrics and gynaecology research 12 38480480
2022 OTUB2 promotes the progression of endometrial cancer by regulating the PKM2-mediated PI3K/AKT signaling pathway. Cell biology international 11 36316812
2020 OTUB2 Promotes Homologous Recombination Repair Through Stimulating Rad51 Expression in Endometrial Cancer. Cell transplantation 11 32830515
2022 OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma. Biological procedures online 10 35850645
2022 OTUB2 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by PJA1 Deubiquitylation. Cellular and molecular bioengineering 9 35611163
2025 Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke. EMBO molecular medicine 8 40021931
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
2021 OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties. Frontiers in oncology 8 34646768
2023 Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating β-Catenin signaling. American journal of cancer research 7 38058843
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
2022 The Emerging Role of OTUB2 in Diseases: From Cell Signaling Pathway to Physiological Function. Frontiers in cell and developmental biology 6 35309903
2025 OTUB2 contributes to vascular calcification in chronic kidney disease via the YAP-mediated transcription of PFKFB3. Theranostics 5 39776804
2025 OTUB2 promotes proliferation and metastasis of triple-negative breast cancer by deubiquitinating TRAF6. Oncology research 3 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
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 2 39904430
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 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
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