Affinage

USP2

Ubiquitin carboxyl-terminal hydrolase 2 · UniProt O75604

Length
605 aa
Mass
68.1 kDa
Annotated
2026-06-11
100 papers in source corpus 56 papers cited in narrative 56 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

USP2 is a ubiquitin-specific cysteine protease that controls the abundance, surface levels, and signaling output of a broad set of substrates by cleaving ubiquitin isopeptide bonds, thereby acting as a hub deubiquitinase coupling protein stability to cell death, circadian, immune, ion-channel, and metabolic programs (PMID:9325273, PMID:27681596). Its catalytic mechanism relies on a conserved active site in which Asn271 stabilizes the oxyanion and Asp575 contributes both to oxyanion-hole formation and to aligning the catalytic His557, and substrate recognition requires simultaneous engagement of two ubiquitin surfaces with water-mediated contacts, including molecular determinants (Ub residues 4, 12, 14, 72) that let the enzyme discriminate ubiquitin from NEDD8 (PMID:16905103, PMID:21542621, PMID:28536428). The enzyme stabilizes substrates predominantly by removing K48-linked polyubiquitin to block proteasomal or lysosomal/endosomal degradation — exemplified by cyclin D1, ErbB2 at endosomes, SKP2, PD-L1 at K270, VPRBP (an upstream p53 repressor), CD47, PPARγ at defined lysines, and PML-RARα (PMID:27681596, PMID:32327714, PMID:34425107, PMID:37670038, PMID:37024504, PMID:40379682, PMID:40993213); it can also resolve K27- and K48-linked chains on SMAD7 to restrain TGF-β signaling and edit K63-linked chains on BMAL1 and TRAF6 to modulate clock and NF-κB outputs (PMID:35332268, PMID:40540897, PMID:40877242). Isoform-specific N-terminal domains dictate substrate selectivity: ENaC deubiquitylation requires the USP2-45 N-terminal tail that docks the enzyme onto Nedd4-2, whereas the catalytic core alone is fully active toward ubiquitin-AMC but deficient against ENaC (PMID:21478478). Through these activities USP2 governs the circadian clock — deubiquitinating PER1 and BMAL1, with Usp2-null mice showing lengthened free-running period, and acting within the suprachiasmatic nucleus to tune photic entrainment (PMID:23213472, PMID:21966515, PMID:39967311) — and operates as a regulatable node, recruited to DNA double-strand breaks by ATM-dependent phosphorylation to stabilize NBS1 and the MRN complex, targeted for degradation by the SPOP E3 ligase, and activated by TGFβ1-driven Lys447 lactylation that is reversed by SIRT2 (PMID:36436562, PMID:41534899, PMID:41310079). Spatial control is added by PEX5-mediated peroxisomal import via a C-terminal PTS1 signal, which sequesters USP2 from cytosolic partners and limits its proapoptotic activity (PMID:26484888). USP2 is druggable: the selective inhibitor ML364 binds USP2 directly and triggers cyclin D1 degradation and cell-cycle arrest, and additional chemical probes (6-thioguanine, gambogic acid at Cys284) inhibit the enzyme through distinct allosteric and noncompetitive modes (PMID:27681596, PMID:29449607, PMID:39807309).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Established that the USP2 ortholog is a bona fide ubiquitin-specific isopeptidase that recycles ubiquitin rather than degrading conjugated substrates, defining its core biochemical activity.

    Evidence In vitro assays with purified recombinant chick UBP41 on 125I-ubiquitin and ubiquitin-fusion substrates, with active-site inhibitor controls

    PMID:9325273

    Open questions at the time
    • Did not identify physiological substrates
    • No structural basis for ubiquitin recognition
  2. 2003 Medium

    Linked USP2 catalytic activity to a cellular outcome by showing overexpression drives apoptosis dependent on the active site, while isoforms can oligomerize and localize to the cytoplasm.

    Evidence Overexpression of wild-type vs. catalytic-mutant UBP41 with apoptosis/flow assays; Co-IP and immunolocalization of mouse Usp2-45/Usp2-69

    PMID:12566314 PMID:14686789

    Open questions at the time
    • Proapoptotic substrate not identified
    • Did not stabilize classical substrates p21/p27
    • Physiological relevance of overexpression phenotype unclear
  3. 2006 High

    Resolved how USP2 recognizes ubiquitin, showing two simultaneous ubiquitin interaction surfaces and ordered water-mediated contacts as a general USP recognition mode.

    Evidence X-ray crystallography of the USP2 catalytic domain–ubiquitin complex with mutant inhibition assays

    PMID:16905103

    Open questions at the time
    • Catalytic triad chemistry not yet functionally dissected
    • Linkage specificity not addressed structurally
  4. 2012 High

    Dissected the catalytic mechanism and substrate engagement kinetics, redefining triad assignments and revealing conformational rearrangement during diubiquitin cleavage.

    Evidence Site-directed mutagenesis with Ub-AMC and K48-diUb hydrolysis assays, MD simulation; stopped-flow single-turnover kinetics with inactive mutant controls

    PMID:21542621 PMID:23211065

    Open questions at the time
    • Mechanism inferred from minimal substrates, not full-length physiological substrates
    • How conformational change selects chain linkage unresolved
  5. 2011 High

    Defined isoform-specific substrate selectivity for membrane channels, showing the USP2-45 N-terminal tail positions the enzyme on Nedd4-2 to deubiquitylate ENaC, KCNQ1, and (later) Cav1.2 to control surface expression.

    Evidence Co-IP and GST pull-down of purified proteins, Xenopus oocyte and mammalian electrophysiology, surface biotinylation, with isoform-specific controls

    PMID:21478478 PMID:22024150 PMID:25366495

    Open questions at the time
    • Structural basis of N-terminal tail substrate positioning not solved
    • Cav1.2 work is Medium confidence single lab
  6. 2011 High

    Established USP2 as a circadian clock regulator that deubiquitinates PER1 and controls BMAL1 turnover, with knockout mice showing altered free-running period and light entrainment, later localized to the suprachiasmatic nucleus.

    Evidence Usp2 knockout (including SCN- and retina-specific conditional) mice, Co-IP, in vitro deubiquitination, locomotor rhythm recording, in vivo Per1/p-ERK induction

    PMID:21966515 PMID:23213472 PMID:39967311

    Open questions at the time
    • PER1 deubiquitination occurs without stability change — functional consequence unclear
    • Ubiquitin chain linkage on clock substrates partly undefined
  7. 2011 Medium

    Connected USP2 to inflammatory and apoptotic signaling, showing it is required for TNF-α-induced NF-κB activation and stabilizes the proapoptotic factor tAIF against CHIP-mediated degradation.

    Evidence siRNA knockdown with IκB/NF-κB readouts and IL-8 ELISA; Co-IP, KD/OE, and cell-death assays for tAIF

    PMID:21293491 PMID:21480224

    Open questions at the time
    • Direct NF-κB-pathway substrate not defined in these studies
    • Single-lab findings without reciprocal in vivo validation
  8. 2015 Medium

    Showed spatial regulation of USP2 by PEX5-dependent peroxisomal import that sequesters the enzyme from cytosolic partners to limit proapoptotic activity, while early metabolic substrates (IDOL/LDLR, MR) were identified.

    Evidence PTS1-modified isoform overexpression, PEX5 KD/OE, FRAP imaging, apoptosis assays; Co-IP and functional uptake/reporter assays for IDOL-LDLR and MR

    PMID:23548632 PMID:26484888 PMID:26666640

    Open questions at the time
    • Fraction of cellular USP2 that is peroxisomal under physiological conditions unknown
    • IDOL/LDLR and MR studies single-lab
  9. 2016 High

    Validated USP2 as a druggable target by identifying ML364, a direct-binding inhibitor that induces cyclin D1 degradation, cell-cycle arrest, and reduced HR repair.

    Evidence Fluorescent di-ubiquitin biochemical assay, microscale thermophoresis binding, Western blot, flow cytometry, HR repair assay

    PMID:27681596

    Open questions at the time
    • Direct cyclin D1 deubiquitination not biochemically reconstituted in this study
    • Selectivity across DUB family not exhaustively profiled
  10. 2018 High

    Expanded the chemical-probe toolkit and defined distinct inhibition modes, including noncompetitive slow-binding inhibition by 6-thioguanine and covalent allosteric inhibition at Cys284 by gambogic acid.

    Evidence Enzyme kinetics and X-ray crystallography (6-thioguanine); covalent binding characterization with functional KRAS readouts (gambogic acid)

    PMID:29449607 PMID:39807309

    Open questions at the time
    • Cellular selectivity of covalent probe not fully resolved
    • Gambogic-acid study is Medium confidence single lab
  11. 2022 Medium

    Established USP2 as a DNA-damage-response component recruited to double-strand breaks by ATM phosphorylation to stabilize NBS1 and the MRN complex, defining post-translational control of USP2 activity at chromatin.

    Evidence DUB screen, Co-IP, chromatin fractionation at DSBs, ATM inhibition, double siRNA knockdown with USP28, HR repair assay

    PMID:36436562

    Open questions at the time
    • Specific ATM phosphosites mapped only as N-terminal residues
    • Redundancy with USP28 complicates attribution
  12. 2023 Medium

    Positioned USP2 as a regulator of tumor immune evasion by stabilizing PD-L1 (K48 chains at K270), CD47, and the p53-repressor VPRBP, nominating it as an immuno-oncology target sparing normal tissue.

    Evidence sgRNA screens, Co-IP, K48-linkage-specific ubiquitination assays, mutagenesis, phagocytosis assays, in vivo tumor models with immune profiling and anti-PD1 combination

    PMID:37024504 PMID:37670038 PMID:40379682

    Open questions at the time
    • Whether one or multiple immune substrates dominate the therapeutic effect unresolved
    • Most mechanistic detail from individual labs
  13. 2025 Medium

    Revealed metabolic deubiquitination programs and a novel activating PTM, showing USP2 stabilizes PPARγ at defined lysines to drive lipid accumulation, muscle insulin sensitivity, and thermogenesis, and is switched on by TGFβ1-driven Lys447 lactylation reversed by SIRT2.

    Evidence Site-specific K48 ubiquitination mapping, mutagenesis, global/tissue-specific KO mice, lactylation mapping and SIRT2 delactylation assays, fibrosis and metabolic models

    PMID:39874418 PMID:40189098 PMID:40993213 PMID:41310079

    Open questions at the time
    • Lactylation finding is recent single-lab
    • How lactylation mechanistically activates catalysis not structurally defined
  14. 2025 Medium

    Identified upstream control of USP2 levels by the SPOP E3 ligase and transcriptional regulators, closing feedback loops onto immune (CD47) and other substrate axes.

    Evidence Co-IP, in vitro deubiquitination, ubiquitination assays, flow cytometry, phagocytosis and syngeneic tumor models

    PMID:41534899

    Open questions at the time
    • SPOP degron on USP2 not finely mapped
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP2 selects among its very large, context-dependent substrate repertoire and which interactions are direct versus scaffold-mediated remains the central open question.
  • No structures of USP2 bound to full-length substrates
  • Cell-type and isoform determinants of substrate choice undefined
  • Several substrates (FOXC1, LEF1, JUP, MMP2, p53-K305R) supported by single Low-confidence studies

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:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0000228 nuclear chromosome 1 GO:0005768 endosome 1 GO:0005777 peroxisome 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9909396 Circadian clock 3 R-HSA-73894 DNA Repair 1
Partners
CD47NEDD4-2PD-L1PPARGSKP2SMAD7SPOPVPRBP
Complex memberships
CLOCK/BMAL1 circadian complexMRE11-RAD50-NBS1 (MRN) complex

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Crystal structure of the human USP2 catalytic domain in complex with ubiquitin revealed that ubiquitin uses two major interaction sites simultaneously for binding to USP2, and a layer of ordered water molecules mediates key interactions between ubiquitin and USP2, suggesting a general mechanism of water-mediated ubiquitin recognition by USPs. X-ray crystallography, ubiquitin mutant inhibition assays, peptide inhibition assays Structure High 16905103
1997 Chick UBP41 (USP2 ortholog) is a ubiquitin-specific protease (cysteine protease) with isopeptidase activity; it cleaves ubiquitin from the C-terminus of natural and engineered ubiquitin fusions regardless of size, releases free ubiquitin from di-ubiquitin, and converts poly-ubiquitinated lysozyme conjugates to mono-ubiquitinated forms without further degradation, suggesting a role in ubiquitin recycling. The enzyme is inhibited by ubiquitin-aldehyde and sulfhydryl-blocking agents. In vitro enzyme assay with purified recombinant protein, 125I-labeled ubiquitin substrates, ubiquitin-β-galactosidase fusion substrates The Journal of biological chemistry High 9325273
2003 Mouse Usp2-69 isoform can form a homo-complex and a hetero-complex with Usp2-45. Both isoforms localize to the cytoplasm when overexpressed in COS-7 and NIH3T3 cells. Co-immunoprecipitation, overexpression in COS-7 and NIH3T3 cells, immunohistochemistry Gene expression Medium 14686789
2003 Overexpression of UBP41 (USP2) is sufficient to induce apoptosis in human cells; an enzymatically defective UBP41 mutant did not induce cell death, demonstrating that the proapoptotic activity requires catalytic activity. Overexpression caused broad deubiquitination but did not stabilize known proteasome substrates p21 or p27, and did not arrest cells in G2/M. Overexpression of wild-type and catalytic mutant UBP41, apoptosis assays, flow cytometry, Western blot Cancer research Medium 12566314
2011 USP2 deubiquitinates and stabilizes truncated AIF (tAIF), promoting AIF-mediated caspase-independent cell death. CHIP ubiquitin E3 ligase antagonizes this by ubiquitinating and destabilizing tAIF. Knockdown of USP2 attenuated MNNG-induced cell death. Co-immunoprecipitation, siRNA knockdown, overexpression, Western blot for tAIF ubiquitination and stability, cell death assays Cell death and differentiation Medium 21293491
2011 USP2 is required for TNF-α-induced NF-κB signaling; siRNA knockdown of USP2 prevented IκB phosphorylation, nuclear translocation of NF-κB, expression of NF-κB target genes, and IL-8 secretion. Isoform-specific functions were identified. Targeted siRNA screen, Western blot for IκB phosphorylation and NF-κB translocation, IL-8 ELISA International journal of cancer Medium 21480224
2011 USP2 coimmunoprecipitates with clock proteins and directly interacts with PER1, deubiquitinating PER1 without altering its stability. Usp2 knockout mice display a longer free-running circadian period and altered clock gene expression. Co-immunoprecipitation, Usp2 knockout mouse model, locomotor rhythm recording, in vitro deubiquitination assay, Western blot Biology open High 23213472
2011 USP2b is in a complex with BMAL1 and regulates its stability and turnover, altering expression of CLOCK/BMAL1-controlled genes; USP2 knockout increases phase delays in response to low irradiance light. Co-immunoprecipitation, USP2 knockout mouse model, luciferase reporter, Western blot PloS one Medium 21966515
2011 USP2-45 physically interacts with ENaC subunits (via the α-ENaC cytoplasmic N-terminal domain) and with the HECT domain of Nedd4-2 (by both its catalytic domain and N-terminal tail), promoting ENaC deubiquitylation and increased surface expression. The Usp2-69 isoform, which lacks the specific N-terminal domain, is inactive toward ENaC. The catalytic core alone has reduced activity toward ENaC in oocytes despite retaining full activity toward ubiquitin-AMC. Co-immunoprecipitation in HEK293 cells, GST pull-down of purified recombinant proteins, Xenopus laevis oocyte electrophysiology American journal of physiology. Renal physiology High 21478478
2011 USP2-45 and USP2-69 both counteract Nedd4-2-mediated downregulation of KCNQ1/KCNE1 channels by deubiquitylating KCNQ1, restoring surface expression and membrane localization. USP2 binds KCNQ1 independently of the PY motif. Electrophysiology in Xenopus oocytes and mammalian cells, co-immunoprecipitation, Western blot for ubiquitin and surface KCNQ1, immunocytochemistry Heart rhythm High 22024150
2011 USP2 contributes to active site catalysis through a conserved Asn271 that directly stabilizes the oxyanion in the acylation step, structurally supported by absolutely conserved Asp575. Asn574, positioned as the putative third catalytic triad member, does not fulfill this role functionally. Asp575 has a dual role in oxyanion hole formation and maintaining His557 alignment. Site-directed mutagenesis, in vitro hydrolysis assays (ubiquitin-AMC, K48-linked diubiquitin), mass spectrometry-based assay, molecular dynamics simulation Biochemistry High 21542621
2012 Stopped-flow kinetics revealed that monoubiquitin binds USP2 in a simple one-step process, while K48-linked diubiquitin shows biphasic binding, indicating a conformational rearrangement of the diubiquitin substrate during USP2 catalysis. Stopped-flow fluorescence kinetics, single-turnover deubiquitination assays with Ub-AMC and K48-linked IQF-diubiquitin, inactive USP2 mutant binding studies Biochemistry High 23211065
2014 USP2-45 binds the α2δ-1 accessory subunit (but not Cav1.2 or β2 subunits) of voltage-gated calcium channels and promotes deubiquitylation of both Cav1.2 and α2δ-1 subunits, reducing Cav1.2 current amplitude and surface expression. Co-expression of α2δ-1 is required for the effect of USP2-45. Whole-cell current recordings, surface biotinylation assays, co-immunoprecipitation in tsA-201 and HEK-293 cells Pflugers Archiv Medium 25366495
2015 USP2 (both USP2-69 and USP2-45 isoforms) interacts with the E3-ubiquitin ligase IDOL and promotes its deubiquitylation, stabilizing IDOL protein. Paradoxically, in a tri-partite USP2-IDOL-LDLR complex, USP2 also deubiquitylates the LDLR and prevents its IDOL-mediated lysosomal degradation, thereby increasing LDL uptake. Genetic screening, co-immunoprecipitation, Western blot for protein stability, LDL uptake assay Circulation research Medium 26666640
2015 USP2-45 binds MR (mineralocorticoid receptor) and, similarly to aldosterone, promotes removal of MR monoubiquitylation, disrupts MR/TSG101 association, and destabilizes MR protein, constituting a negative feedback loop limiting aldosterone-induced responses. Co-immunoprecipitation, Western blot for MR ubiquitylation and stability, luciferase reporter for MR transcriptional activity Cellular physiology and biochemistry Medium 23548632
2016 USP2-45 functions as a circadian clock output effector regulating calcium absorption. In the small intestine, USP2-45 is found in membrane fractions, negatively regulates NHERF4 protein abundance in a rhythmic manner, and interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain. Usp2 knockout mice show hyperabsorption of dietary Ca2+ associated with strong NHERF4 overexpression and TRPV6 upregulation. Usp2 knockout mouse model, subcellular fractionation, in vitro interaction assay (Co-IP), dietary calcium measurement, Drosophila dUsp2 knockdown rescue with dietary Ca2+ PloS one Medium 26756164
2016 USP2 inhibitor ML364 (IC50 1.1 µM) induces cyclin D1 degradation and cell cycle arrest in colorectal cancer and mantle cell lymphoma cells, and decreases homologous recombination-mediated DNA repair. Direct binding of ML364 to USP2 was demonstrated. Fluorescent di-ubiquitin biochemical assay, microscale thermophoresis, Western blot, flow cytometry, HR repair assay The Journal of biological chemistry High 27681596
2017 Residues Ub4K, Ub12E, Ub14E, and Ub72A serve as the molecular determinants enabling USP2 to distinguish between ubiquitin and NEDD8. Combining NEDD8 residues at positions 4, 12, 14, and 72 to match ubiquitin makes NEDD8 accessible for hydrolysis by USP2. USP2 binds the N-terminus of ubiquitin to form a stable interaction before engaging the C-terminus for substrate specificity. Ubiquitin/NEDD8 mutagenesis, in vitro hydrolysis assays Scientific reports High 28536428
2018 6-Thioguanine inhibits USP2 through a noncompetitive and slow-binding mechanism. X-ray crystallographic data confirmed the binding mode. Enzyme kinetics, X-ray crystallography Scientific reports High 29449607
2019 USP2 promotes Twist protein stabilization by removing β-TrCP-mediated ubiquitination of Twist, maintaining cancer stem cell populations in TNBC through Twist-mediated EMT and Bmi1 activation. Co-immunoprecipitation, ubiquitination assay, genetic and pharmacological USP2 inhibition, Western blot, in vivo xenograft Cell death & disease Medium 30918246
2020 USP2 associates with internalized ErbB2 at endosomes and prevents its lysosomal sorting and degradation by exerting deubiquitylase activity, safeguarding ErbB2 surface levels against ubiquitylation-mediated endocytic degradation. Co-immunoprecipitation, Western blot for ErbB2 ubiquitylation, endocytic trafficking assays, USP2 inhibitor ML364 Cell death and differentiation Medium 32327714
2021 USP2 is a deubiquitylase of SKP2, binding via the leucine-rich repeat substrate-binding domain on SKP2 to deubiquitylate and stabilize SKP2 protein. USP2-stabilized SKP2 does not destabilize its substrates p21 and p27 because USP2 binding to SKP2 disrupts the SKP2-substrate interaction. DUB panel screening by Co-IP with endogenous SKP2, siRNA knockdown, small-molecule inhibition, CHX chase assay, ubiquitination assay The Journal of biological chemistry Medium 34425107
2022 USP2 stabilizes E2F4 protein through physical interaction and deubiquitination, promoting E2F4-driven transcription of ATG2A and ULK2, resulting in autophagic degradation of metallothionein proteins and altered zinc homeostasis in cancer cells. Co-immunoprecipitation, deubiquitination assay, BiFC, gain/loss-of-function studies, ChIP, rescue experiments Autophagy Medium 35253629
2022 USP2 interacts with SMAD7 and stabilizes it by cleaving Lys27- and Lys48-linked poly-ubiquitin chains. Lys27-linked poly-ubiquitin chains at SMAD7 K185 mediate SMAD7 recruitment to HERC3, which in turn regulates Lys63-linked polyubiquitination of SMAD7. Loss of USP2 induces TGF-β signaling and glioblastoma progression. Co-immunoprecipitation, in vitro deubiquitination assay distinguishing linkage types, USP2 knockout/overexpression, in vivo GBM model Oncogene Medium 35332268
2022 USP2 deubiquitinates NBS1, stabilizing the MRE11-RAD50-NBS1 complex at DNA double-strand break (DSB) sites. USP2 is recruited to DSB sites in an ATM-dependent manner, and phosphorylation of two critical N-terminal residues of USP2 by ATM is required for recruitment and interaction with RECQL4. Loss of both USP2 and USP28 causes premature MRN disassembly from DSBs, defects in ATM activation, and impaired homologous recombination repair. DUB screen, co-immunoprecipitation, chromatin fractionation at DSBs, ATM kinase inhibition, siRNA double knockdown, HR repair assay The Journal of biological chemistry Medium 36436562
2023 USP2 directly interacts with PD-L1 and deconjugates K48-linked polyubiquitination at lysine 270 of PD-L1, stabilizing PD-L1. Key residues Thr288, Arg292, and Asp293 of USP2 control its binding to PD-L1. USP2 depletion causes ER-associated degradation of PD-L1. sgRNA screening, co-immunoprecipitation, ubiquitination assay (K48-specific), site-directed mutagenesis, Western blot, in vivo tumor models with immune profiling Cell death and differentiation High 37670038
2023 USP2 deubiquitinates and stabilizes VPRBP, a potent repressor of p53. The USP2-VPRBP axis controls both p53 and PD-L1 expression, and USP2 knockout in mice does not affect normal tissues (unlike MDM2 inhibition). Co-immunoprecipitation, Western blot for VPRBP ubiquitination, USP2 knockout mice, genetic and pharmacological inhibition combined with anti-PD1 Nature communications Medium 37024504
2023 USP2 directly interacts with CD47 and stabilizes it through deubiquitination. USP2 inhibition destabilizes CD47, enhancing macrophage phagocytosis of tumor cells. Co-immunoprecipitation, ubiquitination assay, in vitro deubiquitination, phagocytosis assay, in vivo tumor models, single-cell RNA sequencing Nature communications Medium 40379682
2023 USP2 interacts with survivin and stabilizes it; pharmacological inhibition of USP2 by ML364 increases survivin ubiquitination and degradation, sensitizing cancer cells to TRAIL-induced apoptosis. Co-immunoprecipitation, ubiquitination assay, Western blot, cell death assay with survivin overexpression rescue International journal of molecular sciences Medium 37628997
2023 USP2 deubiquitinates ACE2, serving as its physiological deubiquitinase; targeted inhibition with ML364 leads to marked and reversible reduction in ACE2 protein abundance, blocking ACE2-dependent coronavirus infection in vitro and in vivo. USP2 inhibitor ML364, Co-immunoprecipitation, Western blot for ACE2 ubiquitination, viral infection assays, human ACE2 transgenic mouse models Science translational medicine Medium 38055802
2024 USP2 stably binds NCOA4 and suppresses its degradation by removing K48-linked ubiquitin chains from NCOA4, thereby enabling ferritinophagy and ferroptosis in esophageal squamous cell carcinoma cells. Co-immunoprecipitation, ubiquitination assay (K48-specific), USP2 KO in ESCC model, in vitro and in vivo ferroptosis assays Oncogene Medium 38744953
2024 VCP recruits USP2 to FASN, and USP2 removes K48-linked ubiquitin chains from FASN to stabilize it; VCP domain 2 and a specific USP2 amino acid sequence are critical for their interaction. This stabilization promotes autophagy in osteosarcoma. Co-IP/MS, ubiquitination assay, molecular docking, protein truncation mapping, gain/loss-of-function experiments Cell death & disease Medium 39489738
2024 USP2 deubiquitinates and stabilizes EZH2 by directly binding to it and reducing its ubiquitination; USP2-stabilized EZH2 promotes H3K27me3 enrichment and epigenetic silencing of SOX1 in bladder cancer. Co-immunoprecipitation, ubiquitination assay, CHX chase, ChIP assay, in vivo xenograft Translational oncology Medium 39197387
2024 USP2 deubiquitinates and stabilizes MFN2 in cardiomyocytes, counteracting Angiotensin II-induced calcium overload and mitochondrial dysfunction. Rescue experiments confirmed that MFN2 downregulation abolishes the protective role of USP2. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown, in vitro and in vivo cardiac hypertrophy models Molecular and cellular endocrinology Medium 37100191
2024 USP2 deubiquitinates and stabilizes KRAS in multiple myeloma cells. Gambogic acid forms a covalent bond with USP2 Cys284 through an allosteric pocket, inhibiting USP2 deubiquitinating activity and causing KRAS degradation. Co-immunoprecipitation, ubiquitination assay, covalent binding characterization, USP2 knockdown/overexpression, in vitro and in vivo proliferation assays Acta pharmaceutica Sinica. B Medium 39807309
2025 USP2 directly interacts with PPAR-γ and deubiquitinates it by removing K48-linked ubiquitin chains at lysine 161, stabilizing PPAR-γ protein and enhancing its transcriptional activity to promote hepatic lipid accumulation in MASLD. Co-immunoprecipitation, K48-specific ubiquitination assay, site-specific mutagenesis, KO mice, in vivo siRNA targeting, Western blot Cell death and differentiation High 40993213
2025 USP2 directly interacts with PPAR-γ and deubiquitinates it to stabilize protein levels, enhancing insulin signaling and muscle mass maintenance. MYOD1 activates USP2 transcription by binding to the USP2 promoter region. Loss of PPAR-γ abolishes the regulatory effects of USP2 on insulin sensitivity and muscle atrophy. Co-immunoprecipitation, ubiquitination assay, USP2 knockout mouse models (global and muscle-specific), promoter binding assay, AAV-Usp2 injection Diabetes Medium 39874418
2025 USP2 deubiquitinates TXNDC5 (stabilizing TGFβR1 to activate TGF-β signaling) and the transferrin receptor TFRC (enhancing ferroptosis). TGF-β1 activates USP2 by lactylation at Lys447, while SIRT2 delactylates USP2 at Lys447 to suppress its activity. Co-immunoprecipitation, ubiquitination assay, lactylation mapping, SIRT2 delactylation assay, tissue-specific KO mice, organ fibrosis models, ML364 treatment Communications biology Medium 41310079
2025 USP2 deubiquitinates and stabilizes p300 histone acetyltransferase in hepatic stellate cells, promoting fibrogenic responses and HSC activation. DUB inhibitor screen in activated HSCs, co-immunoprecipitation, Western blot for p300 stability, USP2 knockdown/pharmacological inhibition FEBS letters Medium 41703985
2025 USP2 deubiquitinates PML-RARα, including its drug-resistant mutants, stabilizing the fusion protein. USP2 inhibition or silencing reduces PML-RARα protein in an ATRA-sensitive and ATRA-resistant manner, reversed by proteasome inhibition. Co-immunoprecipitation, ubiquitination assay, proteasome inhibition rescue, USP2 overexpression/knockdown, ML364 treatment, apoptosis assay Acta biochimica et biophysica Sinica Medium 41445506
2025 USP2 interacts with and deubiquitinates EBF2 in brown adipose tissue, stabilizing EBF2 protein and mediating thermogenic gene expression (including UCP1). BAT-specific Usp2 knockdown or systemic USP2 inhibition impairs thermogenic programs; Usp2 overexpression in BAT protects against high-fat diet-induced obesity. Quantitative proteomics, co-immunoprecipitation, immunofluorescence, adeno-associated virus-mediated Usp2 manipulation, seahorse metabolic analysis, electron microscopy Molecular metabolism Medium 40189098
2025 SPOP E3 ubiquitin ligase ubiquitinates USP2, leading to its degradation and decreased CD47 protein abundance. USP2 deubiquitinates CD47 and protects it from proteasome-mediated degradation, confirming the SPOP/USP2/CD47 regulatory axis. Co-immunoprecipitation, in vitro deubiquitination assay, ubiquitination assay, cell fractionation, flow cytometry, phagocytosis assay, syngeneic tumor models Journal for immunotherapy of cancer Medium 41534899
2025 USP2 attenuates TRAF6 K63-linked polyubiquitination in intestinal epithelial cells, dampening NF-κB activation and myosin light chain phosphorylation to preserve tight junction integrity. Colonic-specific USP2 overexpression in mice ameliorated DSS-induced barrier damage. Co-immunoprecipitation, K63-specific ubiquitination assay, Western blot for NF-κB/MLCK/MLC phosphorylation, in vivo colitis model with colonic USP2 overexpression International immunopharmacology Medium 40540897
2025 USP2 directly interacts with FOXC1 and deubiquitinates it, stabilizing FOXC1 protein and protecting neuronal cells from MPP+-induced injury. Co-immunoprecipitation, Western blot for ubiquitination/stability, overexpression rescue, cell viability and apoptosis assays Brain research Low 40355038
2025 USP2 stabilizes LEF1 protein by mediating LEF1 deubiquitination, promoting osteogenic differentiation of bone marrow mesenchymal stem cells. Increased USP2 expression reduced bone loss in ovariectomy mouse model. Co-immunoprecipitation, protein stability assay, USP2/LEF1 knockdown, in vivo OVX mouse model Journal of orthopaedic surgery and research Low 40301985
2025 In the suprachiasmatic nucleus (SCN), USP2 modulates photic entrainment of the circadian clock by regulating light-induced Per1 expression and MAPK/ERK pathway activation. SCN-specific Usp2 KO recapitulates the light entrainment phenotype of full-body KO, while retinal Usp2 KO does not. Conditional Usp2 knockout (SCN-specific and retina-specific), running wheel recordings, in vivo light induction of Per1 and p-ERK in SCN Journal of neurochemistry Medium 39967311
2021 USP2 interacts with TRAF2 and removes its ubiquitination chains, stabilizing TRAF2 protein in fibroblast-like synoviocytes and promoting NF-κB-related inflammation in rheumatoid arthritis. Co-immunoprecipitation, ubiquitination assay, Western blot, in vivo CIA rat model Biochemical genetics Low 38480669
2015 Peroxisomal import of USP2 is mediated by PEX5 (PTS1 receptor) recognizing a C-terminal PTS1 signal; this import reduces USP2 proapoptotic activity by spatially separating it from cytosolic and nuclear interaction partners. All four USP2 isoforms are post-translationally imported into peroxisomes. Overexpression of USP2 isoforms with modified PTS1, apoptosis assays, PEX5 knockdown/overexpression, live-cell imaging (FRAP) PloS one Medium 26484888
2024 DCAF7 recruits USP2 to suppress clockophagy (selective autophagic degradation of BMAL1) by reducing BMAL1 K63-linked polyubiquitination, thereby inhibiting ferroptosis through the HIF1α-SLC7A11 axis in hepatocellular carcinoma. Co-immunoprecipitation, K63-specific ubiquitination assay, genetic ablation of DCAF7/USP2, in vitro and in vivo HCC models Cell death & disease Medium 40877242
2025 USP2 deubiquitinates and stabilizes JUP (junction plakoglobin), blocking Akt/β-catenin pathway activation to protect against cardiac hypertrophy. Mycn transcriptionally activates USP2 expression by binding to the USP2 promoter. Co-immunoprecipitation, ubiquitination assay, luciferase promoter assay, gain/loss-of-function in ISO-induced cardiac hypertrophy models BMC cardiovascular disorders Low 38297207
2025 USP2 deubiquitinates and stabilizes TRAF2 in nasopharyngeal carcinoma, promoting NF-κB signaling, and directly binds MMP2 to reduce K48-linked polyubiquitination, extending MMP2 protein half-life. Co-immunoprecipitation, ubiquitination assay (K48-specific), CHX chase assay, NF-κB inhibition rescue Molecular carcinogenesis Low 41144793
2025 USP2 deubiquitinates and stabilizes PPARγ by removing K48-linked chains at the K142 site, promoting fatty acid biosynthesis in hepatocellular carcinoma and oleic acid-mediated M2 macrophage polarization, which creates an IL-10/STAT3/USP2 positive-feedback loop. Co-immunoprecipitation, CUT&RUN, ELISA, mass spectrometry, K48-specific ubiquitination assay, in vitro co-culture system, patient-derived organoids Journal for immunotherapy of cancer Medium 41193183
2024 USP2 reduces Keap1 deubiquitination (stabilizing Keap1), leading to Nrf2 inactivation, impaired iron metabolism, and lipid peroxidation, thereby promoting ferroptosis in macrophages and driving atherosclerosis. USP2 knockout macrophages show elevated Keap1 ubiquitination. USP2 knockout macrophages, ubiquitination assay for Keap1, ferroptosis assays, in vivo atherosclerosis model (apoE-/- mice), USP2 KO mice British journal of pharmacology Medium 39228119
2021 USP2 deubiquitinates and stabilizes antithrombin by counteracting Cullin 2-RBX1-mediated ubiquitination and degradation. USP2 overexpression inhibits antithrombin ubiquitination, while USP2 knockdown or pharmacological inhibition downregulates antithrombin. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, overexpression, proteasome inhibition, neddylation inhibition FASEB journal Medium 34324733
2021 USP2 deubiquitinates and stabilizes TJP1/TWIST1 in bladder cancer; TJP1 acts as a scaffold recruiting USP2 to TWIST1, protecting TWIST1 from proteasomal degradation and promoting CCL2-driven angiogenesis. Co-immunoprecipitation, ubiquitination assay, TJP1/USP2 interaction mapping, in vitro and in vivo rescue experiments Oncogene Medium 34782718
2025 USP2 deubiquitinates and stabilizes p53 at the K305R site, removing ubiquitin to modulate cisplatin resistance through ferroptosis in NSCLC. USP2 overexpression increases nuclear p53 and promotes ferroptosis markers while reducing GPX4 and SLC7A11. Co-immunoprecipitation, ubiquitination assay (site-specific K305R), Western blot, in vivo xenograft BMC medical genomics Low 40011884

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Structural basis of ubiquitin recognition by the deubiquitinating protease USP2. Structure (London, England : 1993) 187 16905103
2016 Small Molecule Inhibition of the Ubiquitin-specific Protease USP2 Accelerates cyclin D1 Degradation and Leads to Cell Cycle Arrest in Colorectal Cancer and Mantle Cell Lymphoma Models. The Journal of biological chemistry 137 27681596
2019 Inhibition of USP2 eliminates cancer stem cells and enhances TNBC responsiveness to chemotherapy. Cell death & disease 70 30918246
2011 Mice lacking the USP2 deubiquitinating enzyme have severe male subfertility associated with defects in fertilization and sperm motility. Biology of reproduction 66 21543767
2023 USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1. Cell death and differentiation 64 37670038
2021 USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes. International journal of molecular sciences 62 33530560
2003 Gene structure, alternate splicing, tissue distribution, cellular localization, and developmental expression pattern of mouse deubiquitinating enzyme isoforms Usp2-45 and Usp2-69. Gene expression 61 14686789
2011 The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light. PloS one 55 21966515
2022 Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression. Autophagy 53 35253629
2011 An RNAi screen identifies USP2 as a factor required for TNF-α-induced NF-κB signaling. International journal of cancer 49 21480224
2020 The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer. Cell death and differentiation 48 32327714
2005 Synthesis and characterization of fluorescent ubiquitin derivatives as highly sensitive substrates for the deubiquitinating enzymes UCH-L3 and USP-2. Analytical biochemistry 47 15963938
1997 Molecular cloning of a novel ubiquitin-specific protease, UBP41, with isopeptidase activity in chick skeletal muscle. The Journal of biological chemistry 47 9325273
2015 The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL. Circulation research 46 26666640
2003 UBP41 is a proapoptotic ubiquitin-specific protease. Cancer research 46 12566314
2015 USP2 promotes cell migration and invasion in triple negative breast cancer cell lines. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 45 25687182
2018 6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2. Scientific reports 44 29449607
2012 Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2. Biology open 43 23213472
2007 Stable activity of a deubiquitylating enzyme (Usp2-cc) in the presence of high concentrations of urea and its application to purify aggregation-prone peptides. Biochemical and biophysical research communications 40 17560941
2014 Identifying USPs regulating immune signals in Drosophila: USP2 deubiquitinates Imd and promotes its degradation by interacting with the proteasome. Cell communication and signaling : CCS 38 25027767
2023 Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy. Nature communications 36 37024504
2011 Control of AIF-mediated cell death by antagonistic functions of CHIP ubiquitin E3 ligase and USP2 deubiquitinating enzyme. Cell death and differentiation 36 21293491
2011 Ubiquitin-specific protease 2-45 (Usp2-45) binds to epithelial Na+ channel (ENaC)-ubiquitylating enzyme Nedd4-2. American journal of physiology. Renal physiology 35 21478478
2010 Genetic variations in the sodium balance-regulating genes ENaC, NEDD4L, NDFIP2 and USP2 influence blood pressure and hypertension. Kidney & blood pressure research 35 20090362
2020 Identification of novel human USP2 inhibitor and its putative role in treatment of COVID-19 by inhibiting SARS-CoV-2 papain-like (PLpro) protease. Computational biology and chemistry 32 32979815
2017 3,3'-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity. Molecular nutrition & food research 31 28586165
2022 Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-β signaling. Oncogene 28 35332268
2017 The Molecular Mechanisms of Regulation on USP2's Alternative Splicing and the Significance of Its Products. International journal of biological sciences 28 29230097
2021 USP2 is an SKP2 deubiquitylase that stabilizes both SKP2 and its substrates. The Journal of biological chemistry 27 34425107
2011 Contribution of active site residues to substrate hydrolysis by USP2: insights into catalysis by ubiquitin specific proteases. Biochemistry 27 21542621
2021 c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA. Cell death & disease 26 34707111
2013 Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain normal sodium balance and blood pressure. American journal of physiology. Renal physiology 26 23552861
2011 Deubiquitylating enzyme USP2 counteracts Nedd4-2-mediated downregulation of KCNQ1 potassium channels. Heart rhythm 26 22024150
2016 USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level. PloS one 25 26756164
2020 lncRNA USP2-AS1 promotes colon cancer progression by modulating Hippo/YAP1 signaling. American journal of translational research 24 33042447
2014 Ubiquitin-specific protease USP2-45 acts as a molecular switch to promote α2δ-1-induced downregulation of Cav1.2 channels. Pflugers Archiv : European journal of physiology 19 25366495
2002 Parathyroid hormone (hPTH 1-38) stimulates the expression of UBP41, an ubiquitin-specific protease, in bone. Journal of cellular biochemistry 19 11948679
2022 LncRNA USP2-AS1 Promotes Hepatocellular Carcinoma Growth by Enhancing YBX1-Mediated HIF1α Protein Translation Under Hypoxia. Frontiers in oncology 18 35692750
2021 Tight junction protein 1 promotes vasculature remodeling via regulating USP2/TWIST1 in bladder cancer. Oncogene 18 34782718
2015 PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression. Calcified tissue international 18 26643174
2023 USP2 inhibition prevents infection with ACE2-dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice. Science translational medicine 17 38055802
2025 USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity. Nature communications 16 40379682
2024 Hypoxia inhibits ferritinophagy-mediated ferroptosis in esophageal squamous cell carcinoma via the USP2-NCOA4 axis. Oncogene 16 38744953
2022 USP2 promotes experimental colitis and bacterial infections by inhibiting the proliferation of myeloid cells and remodeling the extracellular matrix network. Cell insight 16 37192862
2015 Increased acid ceramidase expression depends on upregulation of androgen-dependent deubiquitinases, USP2, in a human prostate cancer cell line, LNCaP. Journal of biochemistry 16 25888580
2012 Transient kinetic analysis of USP2-catalyzed deubiquitination reveals a conformational rearrangement in the K48-linked diubiquitin substrate. Biochemistry 16 23211065
2007 [Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 16 17553343
2024 The plant extract PNS mitigates atherosclerosis via promoting Nrf2-mediated inhibition of ferroptosis through reducing USP2-mediated Keap1 deubiquitination. British journal of pharmacology 15 39228119
2020 Long Non-Coding RNA USP2-AS1 Accelerates Cell Proliferation and Migration in Ovarian Cancer by Sponging miR-520d-3p and Up-Regulating KIAA1522. Cancer management and research 14 33122952
2018 Retigabine ameliorates acute stress-induced impairment of spatial memory retrieval through regulating USP2 signaling pathways in hippocampal CA1 area. Neuropharmacology 14 29501527
2023 Angiotensin II-induced calcium overload affects mitochondrial functions in cardiac hypertrophy by targeting the USP2/MFN2 axis. Molecular and cellular endocrinology 12 37100191
2023 Targeting the deubiquitinase USP2 for malignant tumor therapy (Review). Oncology reports 12 37594087
2022 USP2 Inhibits Lung Cancer Pathogenesis by Reducing ARID2 Protein Degradation via Ubiquitination. BioMed research international 12 36567903
2025 USP2 reversed cisplatin resistance through p53-mediated ferroptosis in NSCLC. BMC medical genomics 11 40011884
2024 The discovery of potent USP2/USP8 dual-target inhibitors for the treatment of breast cancer via structure guided optimization of ML364. European journal of medicinal chemistry 11 38452725
2024 VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN. Cell death & disease 11 39489738
2017 The molecular determinants for distinguishing between ubiquitin and NEDD8 by USP2. Scientific reports 11 28536428
2023 USP2 promotes cell proliferation and metastasis in choroidal melanoma via stabilizing Snail. Journal of cancer research and clinical oncology 10 37199836
2021 Behavioral phenotyping of mice lacking the deubiquitinase USP2. PloS one 10 33621249
2020 Cryptic and atypical KMT2A-USP2 and KMT2A-USP8 rearrangements identified by mate pair sequencing in infant and childhood leukemia. Genes, chromosomes & cancer 10 32196814
2015 Peroxisomal Import Reduces the Proapoptotic Activity of Deubiquitinating Enzyme USP2. PloS one 10 26484888
2010 Expression of USP2-69 in mesangial cells in vivo and in vitro. Pathology international 10 20403044
2023 Inhibition of USP2 Enhances TRAIL-Mediated Cancer Cell Death through Downregulation of Survivin. International journal of molecular sciences 9 37628997
2013 USP2-45 represses aldosterone mediated responses by decreasing mineralocorticoid receptor availability. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 9 23548632
2025 Deubiquitinating Enzyme USP2 Alleviates Muscle Atrophy by Stabilizing PPAR-γ. Diabetes 8 39874418
2022 Hypoxia-Regulated lncRNA USP2-AS1 Drives Head and Neck Squamous Cell Carcinoma Progression. Cells 8 36359803
2019 Whole transcriptome sequencing reveals a KMT2A-USP2 fusion in infant acute myeloid leukemia. Genes, chromosomes & cancer 8 30869817
2018 Halogen Substituents in the Isoquinoline Scaffold Switches the Selectivity of Inhibition between USP2 and USP7. Chembiochem : a European journal of chemical biology 8 30474907
2016 Usp2-69 overexpression slows down the progression of rat anti-Thy1.1 nephritis. Experimental and molecular pathology 8 27640956
2024 Mycn ameliorates cardiac hypertrophy-induced heart failure in mice by mediating the USP2/JUP/Akt/β-catenin cascade. BMC cardiovascular disorders 7 38297207
2024 The role of deubiquitinase USP2 in driving bladder cancer progression by stabilizing EZH2 to epigenetically silence SOX1 expression. Translational oncology 7 39197387
2024 USP2 Mitigates Reactive Oxygen Species-Induced Mitochondrial Damage via UCP2 Expression in Myoblasts. International journal of molecular sciences 7 39596006
2022 Deubiquitinase USP2 stabilizes the MRE11-RAD50-NBS1 complex at DNA double-strand break sites by counteracting the ubiquitination of NBS1. The Journal of biological chemistry 7 36436562
2025 Lactate orchestrates the TGFβ pathway and ferroptosis nexus in organ fibrosis via USP2 lactylation. Communications biology 6 41310079
2021 Cullin 2-RBX1 E3 ligase and USP2 regulate antithrombin ubiquitination and stability. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 34324733
2025 DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis. Cell death & disease 5 40877242
2024 USP2 Promotes the Proliferation and Inflammation of Fibroblast-Like Synovial Cells in Rheumatoid Arthritis Through Deubiquitination of TRAF2. Biochemical genetics 5 38480669
2024 Pharmacological USP2 targeting suppresses ovarian cancer growth by potentiating apoptosis and ferroptosis. Archives of biochemistry and biophysics 5 39486565
2025 USP2 promotes metabolic dysfunction-associated steatotic liver disease progression via stabilization of PPARγ. Cell death and differentiation 4 40993213
2023 In Cerebellar Atrophy of 12-Month-Old ATM-Null Mice, Transcriptome Upregulations Concern Most Neurotransmission and Neuropeptide Pathways, While Downregulations Affect Prominently Itpr1, Usp2 and Non-Coding RNA. Cells 4 37830614
2023 LncRNA USP2-AS1 facilitates the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting KDM3A/ETS1/USP2 to activate the Wnt/β-catenin signaling pathway. RNA biology 4 38131611
2022 Validation of catalytic site residues of Ubiquitin Specific Protease 2 (USP2) by molecular dynamic simulation and novel kinetics assay for rational drug design. Molecular diversity 4 35932436
2025 The Deubiquitinase USP2 Modulates Photic Entrainment of the Circadian Clock at the Level of the Suprachiasmatic Nucleus. Journal of neurochemistry 3 39967311
2025 USP2-mediated PPARγ stabilization promotes hepatocellular carcinoma progression and M2 macrophage polarization via oleic acid. Journal for immunotherapy of cancer 3 41193183
2025 USP2-induced upregulation of LEF1 through deubiquitination relieves osteoporosis development by promoting the osteogenic differentiation of bone marrow mesenchymal stem cells. Journal of orthopaedic surgery and research 2 40301985
2025 Targeting USP2 induces degradation of PML-RARα with or without drug-resistant mutations in acute promyelocytic leukemia. Acta biochimica et biophysica Sinica 2 41445506
2024 Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells. Acta pharmaceutica Sinica. B 2 39807309
2022 Downregulation of lncRNA USP2‑AS1 in the placentas of pregnant women with non‑diabetic fetal macrosomia promotes trophoblast cell proliferation. Molecular medicine reports 2 35674181
2026 CD47 destabilization via manipulating the SPOP-USP2 axis augments macrophage phagocytosis and cancer immunotherapy. Journal for immunotherapy of cancer 1 41534899
2026 Deubiquitinase USP2 promotes hepatic stellate cell activation via p300 stabilization. FEBS letters 1 41703985
2025 Deubiquitinating enzyme USP2 regulates brown adipose tissue thermogenesis via controlling EBF2 stabilization. Molecular metabolism 1 40189098
2025 USP2 alleviates MPP+-induced neuronal injury by stabilizing FOXC1 in SK-N-SH cells. Brain research 1 40355038
2025 The deubiquitinase USP2 preserves intestinal barrier through the TRAF6/NF-κB/MLCK/MLC signaling in ulcerative colitis. International immunopharmacology 1 40540897
2025 Muscular USP2 is dispensable for MASLD-associated disorders in the liver and skeletal muscle in mice. Biomedical research (Tokyo, Japan) 1 41016774
2023 Age-related genes USP2 and ARG2 are involved in the reduction of immune cell infiltration in elderly patients with rheumatoid arthritis. The journal of gene medicine 1 37727011
2026 USP2 Attenuates Spermatogenic Cell Apoptosis Via PINK1/Parkin-Dependent Mitophagy in Varicocoele: A Functional Study. Andrology 0 41960601
2026 Ubiquitin-Specific Protease 2 (USP2) as a Modulator of Energy Metabolism: A Review of Studies Using Animal and Cellular Models. Biomedicines 0 42072324
2026 USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer. Cell death & disease 0 42230533
2025 LncRNA USP2-AS1 facilitates colorectal cancer development through the PHLDA2/PI3K/AKT axis. Experimental cell research 0 40505801
2025 USP2 Promotes Nasopharyngeal Carcinoma Progression by Activating TRAF2/NF-κB Signaling and Stabilizing MMP2. Molecular carcinogenesis 0 41144793

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