Affinage

USP3

Ubiquitin carboxyl-terminal hydrolase 3 · UniProt Q9Y6I4

Length
520 aa
Mass
58.9 kDa
Annotated
2026-06-11
39 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP3 is a chromatin-associated ubiquitin-specific protease that maintains genome stability and shapes signaling by reversing ubiquitination on histone and non-histone substrates (PMID:17980597, PMID:25113974). As an active deubiquitinase first characterized in vitro—uniquely able to cleave a ubiquitin-proline bond—it cleaves ubiquitin from conjugates and antagonizes ubiquitin-dependent degradation (PMID:10480896). Through a catalytic USP domain and a ZnF-UBP ubiquitin-binding domain that first engages polyubiquitin, USP3 dynamically associates with chromatin and removes monoubiquitin from histones H2A and H2B, including H2A/gamma-H2AX at the RNF168-modified K13/K15 sites and at K118/K119; its depletion causes S-phase delay, DNA-break accumulation, and checkpoint activation, while ectopic USP3 counteracts RNF168/RNF8 signaling and limits BRCA1 and 53BP1 recruitment to damage sites (PMID:17980597, PMID:24196443, PMID:24366338). In vivo, USP3 deletion in mice raises H2A ubiquitination, provokes spontaneous DNA damage, and erodes hematopoietic stem cell self-renewal and lifespan, establishing a physiological role in genome maintenance (PMID:25113974). USP3 also tunes cell-cycle and DNA-damage signaling by removing inhibitory K63-linked chains from CHK1 at K132 to release it from chromatin and open its active site (PMID:29735693). In innate immunity, USP3 strips K63-linked chains from RIG-I (and MDA5) via CARD binding to restrain type I interferon production (PMID:24366338), and stabilizes the inflammasome adaptor ASC by removing K48-linked ubiquitin to promote inflammasome activation (PMID:36050480). Across many cancers, USP3 acts as a deubiquitinase that stabilizes oncogenic and pro-survival substrates—including KLF5, Cdc25A, Aurora A, MYCN, REST, SMARCA5, EPHA2, DNM1L, MIC19, and PD-L1—driving proliferation, genome stability, metabolic rewiring, and immune escape (PMID:31624151, PMID:32415280, PMID:34758762, PMID:33767157, PMID:37170124, PMID:39500888, PMID:38531846, PMID:40770539).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Established that USP3 is a catalytically active deubiquitinase, defining the basic enzymatic identity from which all later substrate work proceeds.

    Evidence In vitro deubiquitinase assay and yeast complementation showing cleavage of ubiquitin conjugates and a ubiquitin-proline bond

    PMID:10480896

    Open questions at the time
    • No physiological substrate identified
    • No structural basis for the unusual ubiquitin-proline cleavage
  2. 2007 High

    Identified histones H2A/H2B as in vivo substrates and tied USP3 to chromatin dynamics and the DNA damage response, answering what USP3 actually does in cells.

    Evidence RNAi knockdown, chromatin fractionation, domain mapping, FRAP/live imaging in human cells

    PMID:17980597

    Open questions at the time
    • Did not resolve which lysine residues are targeted
    • Mechanism of chromatin recruitment not defined
  3. 2013 High

    Mapped the histone targets to RNF168-controlled K13/K15 and K118/K119 and positioned USP3 as a negative regulator of the RNF8/RNF168 ubiquitin cascade, clarifying its role in DSB signaling.

    Evidence Site-directed mutagenesis of H2A/H2AX lysines, immunofluorescence of BRCA1/53BP1 foci, Co-IP

    PMID:24196443

    Open questions at the time
    • Selectivity between histone sites not quantified
    • Regulation of USP3 recruitment to break sites unknown
  4. 2013 High

    Extended USP3 beyond chromatin to innate immune signaling by showing it removes K63 chains from RIG-I/MDA5 to dampen interferon responses.

    Evidence Reciprocal Co-IP, K63-linkage-specific ubiquitination and IFN reporter assays, domain deletion in immune cells

    PMID:24366338

    Open questions at the time
    • In vivo antiviral relevance not tested
    • Whether ZnF-UBP chain binding precedes cleavage on all substrates not generalized
  5. 2014 High

    Demonstrated the in vivo physiological requirement for USP3 in genome maintenance and stem cell homeostasis, moving beyond cell-line phenotypes.

    Evidence Usp3 knockout mouse with HSC reconstitution assays, histone ubiquitination blots, DNA damage and tumor monitoring

    PMID:25113974

    Open questions at the time
    • Substrate(s) responsible for the HSC phenotype not isolated
    • Tissue-specific contributions not dissected
  6. 2018 High

    Resolved a non-histone chromatin substrate by showing USP3 removes inhibitory K63 chains from CHK1 at K132, both releasing it from chromatin and de-repressing its active site.

    Evidence In vitro deubiquitination, CHK1 K132 and USP3 catalytic/NLS mutants, chromatin fractionation and kinase assays

    PMID:29735693

    Open questions at the time
    • Upstream signal directing USP3 to CHK1 unknown
    • Interplay with histone deubiquitination at the same loci unresolved
  7. 2017 Medium

    Opened the oncology substrate program by linking USP3 catalytic activity to p53 stabilization and suppression of cellular transformation.

    Evidence Co-IP, ubiquitination assay, C168S catalytic-mutant rescue, transformation assay

    PMID:28807825

    Open questions at the time
    • Single lab, single study
    • Ubiquitin linkage type and direct deubiquitination not fully defined
  8. 2019 High

    Systematic screening identified KLF5 as a USP3 substrate and provided in vivo evidence that USP3 deubiquitination drives tumor proliferation.

    Evidence Genome-wide siRNA screen, Co-IP, ubiquitination assay, xenograft with KLF5 rescue

    PMID:31624151

    Open questions at the time
    • Linkage specificity on KLF5 not defined
    • Direct vs indirect deubiquitination not separated from cofactors
  9. 2020 Medium

    Expanded the cell-cycle substrate set to Cdc25A and Claspin, connecting USP3 to ATR-CHK1 progression and radioresistance.

    Evidence CRISPR-Cas9 USP-subfamily knockout screen, Co-IP/ubiquitination assays, cell-cycle and radioresistance assays, xenografts

    PMID:31900278 PMID:32415280

    Open questions at the time
    • Catalytic step on Claspin not deeply characterized
    • Whether Cdc25A and Claspin effects are coordinated unknown
  10. 2021 Medium

    Broadened the oncoprotein substrate repertoire to Aurora A, MYCN, and ECM collagens, and revealed transcriptional feedforward loops (MYCN-ALYREF-USP3) that amplify USP3 function.

    Evidence Co-IP, K48/K63-linkage-specific ubiquitination assays, site-directed mutagenesis (Aurora A K143R), transgenic and xenograft models, iTRAQ proteomics

    PMID:33767157 PMID:34758762 PMID:34930901

    Open questions at the time
    • Each substrate validated in one lab
    • Substrate selectivity determinants of USP3 not established
  11. 2022 Medium

    Defined dual ubiquitin-dependent and RNA-binding functions, stabilizing ASC for inflammasome activation and stabilizing APOBEC3G both enzymatically and via mRNA binding.

    Evidence Co-IP, in vitro/K48-linkage-specific deubiquitination assays, RT-PCR mRNA binding, mouse inflammasome and HIV-1 replication models

    PMID:36050480 PMID:36574218

    Open questions at the time
    • RNA-binding determinant within USP3 not mapped
    • Generality of catalysis-independent mRNA stabilization unknown
  12. 2023 Medium

    Showed USP3 substrate engagement is often directed by scaffolds (lncRNAs) and extended its reach to differentiation and stress regulators (REST, AR, SIRT3).

    Evidence CRISPR USP knockout screen, RNA pull-down/RIP, Co-IP, in vitro deubiquitination, proximity assays, xenografts

    PMID:37013584 PMID:37170124 PMID:37348684

    Open questions at the time
    • SIRT3 deubiquitination shown largely indirectly
    • How scaffolds confer substrate specificity not generalized
  13. 2024 Medium

    Mapped a substrate-binding region (F2 domain, residue 203 for EPHA2) and linked USP3 to DNA repair, metabolism, and survival pathways across cancers (SMARCA5, EPHA2/PI3K-AKT, ACOT7/ferroptosis).

    Evidence Co-IP, domain-truncation mapping, K63/K48-linkage-specific ubiquitination assays, rescue and ferroptosis-marker assays, xenografts

    PMID:38502867 PMID:38531846 PMID:39500888

    Open questions at the time
    • Structural basis of substrate recognition not solved
    • ACOT7 axis rests on limited mechanistic depth
  14. 2025 Medium

    Placed USP3 under hypoxic (HIF-1α) and scaffold (RHBDL2) control and extended substrates to mitochondrial and metabolic regulators (DNM1L, MIC19, PPT1, MYC), tying USP3 to mitochondrial dynamics and lipogenesis.

    Evidence ChIP, structural/mutational analysis of RHBDL2-USP3 interface, K48-linkage ubiquitination assays, multi-omics and xenograft/metastasis models

    PMID:40164288 PMID:40197257 PMID:40770539 PMID:42031733

    Open questions at the time
    • USP3-MYC deubiquitination shown only indirectly in one report
    • Coordination among the many metabolic substrates unknown
  15. 2026 Low

    Implicated USP3 in immune evasion by stabilizing PD-L1 and continued cell-cycle substrate expansion to PLK1, reinforcing its pro-tumor role.

    Evidence Co-IP, K48-linkage ubiquitination assays, PBMC co-culture cytotoxicity, knockdown/overexpression, xenografts

    PMID:41525176 PMID:41957704

    Open questions at the time
    • Very recent single reports with limited replication
    • Direct catalytic step on PD-L1 not deeply characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single DUB achieves selectivity across such a broad substrate set—and how its ZnF-UBP/USP domains, scaffolds, and chain-linkage preferences are integrated structurally—remains unresolved.
  • No high-resolution structure of USP3 with a substrate
  • Rules governing K48 vs K63 chain selectivity unknown
  • Determinants distinguishing physiological from opportunistic substrates undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 4 GO:0003723 RNA binding 1
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2
Partners
ASCAURORA ACDC25ACHK1KLF5MDA5MYCNRIG-I

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 USP3 is a functional ubiquitin-specific protease in vitro, capable of cleaving ubiquitin from substrates and inhibiting ubiquitin-dependent degradation of both N-end Rule substrates and abnormal endogenous proteins in yeast. It is also one of only two known USPs capable of efficiently cleaving a ubiquitin-proline bond. In vitro deubiquitinase assay; yeast complementation assay The Journal of biological chemistry High 10480896
2007 USP3 is a deubiquitinating enzyme for monoubiquitinated histone H2A (uH2A) and H2B (uH2B). It dynamically associates with chromatin and deubiquitinates H2A/H2B in vivo. The ZnF-UBP domain of USP3 mediates its interaction with uH2A. RNAi-mediated depletion causes S phase delay, accumulation of DNA breaks, and activation of DNA damage checkpoints. In response to ionizing radiation, USP3 is required for full deubiquitination of ubiquitin-conjugates/uH2A and dephosphorylation of gamma-H2AX. RNAi knockdown, chromatin fractionation, in vivo deubiquitination assay, domain-mapping experiments, live-cell imaging, immunofluorescence, FRAP Current biology : CB High 17980597
2013 USP3 deubiquitinates H2A and gamma-H2AX specifically at lysines 13 and 15 (sites ubiquitinated by RNF168) as well as K118 and K119 of H2AX in response to DNA damage. Ectopic USP3 expression abrogates FK2-reactive ubiquitin-conjugate foci and impairs accumulation of BRCA1 and 53BP1 at DNA damage sites, placing USP3 as a negative regulator counteracting RNF168/RNF8-mediated ubiquitination signaling. Ectopic expression, site-directed mutagenesis of H2A/H2AX lysine residues, immunofluorescence, co-immunoprecipitation Cell cycle (Georgetown, Tex.) High 24196443
2013 USP3 negatively regulates type I interferon signaling by removing K63-linked polyubiquitin chains from RIG-I and MDA5. Upon viral infection or ligand stimulation, USP3 binds the caspase activation recruitment domain (CARD) of RLRs; its zinc-finger ubiquitin-binding domain and USP catalytic domain cooperate to cleave polyubiquitin chains. Binding to polyubiquitin chains is required prior to cleavage. USP3 knockdown enhances K63-linked ubiquitination of RIG-I, increases IRF3 phosphorylation, and augments type I interferon production. Co-immunoprecipitation, siRNA knockdown, ubiquitination assays (K63-linkage specific), IRF3 phosphorylation assay, domain deletion/mutation analysis, IFN reporter assays Cell research High 24366338
2014 Genetic deletion of USP3 in mice (Usp3Δ/Δ) increases histone H2A ubiquitination levels in adult tissues, reduces hematopoietic stem cell (HSC) reserves over time, impairs HSC self-renewal and repopulation potential, and shortens animal lifespan. USP3-deficient HSCs accumulate spontaneous DNA damage and show defective DDR, establishing USP3 as required for genome maintenance and HSC homeostasis in vivo. Usp3 knockout mouse model, hematopoietic reconstitution assays, histone ubiquitination western blot, DNA damage assays, tumor monitoring The Journal of experimental medicine High 25113974
2018 USP3 removes K63-linked ubiquitin chains from CHK1 at residue K132 (located at the kinase active site). This K63-linked ubiquitin chain has an inhibitory effect on CHK1 kinase activity. Wild-type USP3, but not its catalytically defective or nuclear-localization-sequence-deficient mutants, reduces CHK1 K63-linked ubiquitination. USP3 knockdown leads to prolonged CHK1 chromatin association and phosphorylation. USP3 thus plays a dual role: releasing CHK1 from chromatin and opening up its active site to substrates. Deubiquitination assay, site-directed mutagenesis (USP3 catalytic mutant, NLS mutant; CHK1 K132), siRNA knockdown, chromatin fractionation, kinase activity assay Proceedings of the National Academy of Sciences of the United States of America High 29735693
2019 USP3 interacts with KLF5 and stabilizes it via deubiquitination, promoting breast cancer cell proliferation in vitro and tumorigenesis in vivo. Knockdown of USP3 reduces KLF5 protein levels and inhibits proliferation, which is partially rescued by ectopic KLF5 expression. Genome-wide siRNA library screen, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, xenograft tumor assay, rescue experiment The Journal of biological chemistry High 31624151
2020 USP3 is a deubiquitinase for Cdc25A; USP3 depletion reduces Cdc25A protein levels and causes significant delay in cell-cycle progression. Identified via CRISPR-Cas9 genome-scale knockout screen of the entire USP subfamily followed by western blot screening. CRISPR-Cas9 genome-scale USP knockout library screen, western blot for Cdc25A, cell cycle analysis, xenograft tumor model Cell death and differentiation High 32415280
2020 Smoothened (Smo) promotes GBM radioresistance by transcriptionally upregulating USP3, which then deubiquitinates Claspin, preventing its polyubiquitination and proteasomal degradation, thereby sustaining ATR-Chk1 signaling. In vitro and in vivo radioresistance assays, USP3 knockdown/overexpression, ubiquitination assays, co-immunoprecipitation, xenograft model Clinical cancer research Medium 31900278
2017 USP3 interacts with p53 and stabilizes it via deubiquitinase activity. Depletion of USP3 leads to accelerated degradation of p53 and enhanced cell proliferation/transformation. Reconstitution with wild-type USP3, but not the catalytically inactive C168S mutant, restores p53 stability and inhibits transformation. Co-immunoprecipitation, ubiquitination assay, USP3 C168S catalytic mutant rescue, siRNA knockdown, transformation assay Biochemical and biophysical research communications Medium 28807825
2021 USP3 interacts with and stabilizes COL9A3 and COL6A5 via deubiquitination in gastric cancer cells, mediating USP3's pro-tumorigenic activity. Identified by isobaric tags for relative and absolute quantification (iTRAQ) proteomics as downstream targets. iTRAQ proteomics, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, in vivo xenograft model Cell death & disease Medium 34930901
2021 USP3 deubiquitinates Aurora A at K143, suppressing its ubiquitination and proteasomal degradation, thereby promoting proliferation and metastasis of esophageal squamous cell carcinoma. A deubiquitination-mimetic K143R mutant of Aurora A enhances kinase activity and is insensitive to USP3 regulation. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (Aurora A K143R), proliferation and invasion assays BMC cancer Medium 34758762
2021 USP3 stabilizes the MYCN protein by reducing K48- and K63-linked ubiquitination of MYCN. ALYREF forms a nuclear coactivator complex with MYCN that stimulates USP3 transcription, creating a positive feedback axis (MYCN-ALYREF-USP3) to drive MYCN protein stability. Transgenic neuroblastoma models (in vitro and in vivo), co-immunoprecipitation, ubiquitination assays (K48/K63 linkage specific), transcriptional reporter assays Nature communications Medium 33767157
2022 USP3 directly deubiquitinates the inflammasome adaptor ASC, specifically removing K48-linked ubiquitination to block proteasomal degradation and stabilize ASC. This promotes inflammasome assembly and activation in vitro and in mouse models of Alum-induced peritonitis, F. novicida infection, and flagellin-induced pneumonia. Co-immunoprecipitation, in vitro deubiquitination assay, K48-linkage specific ubiquitination assay, mouse inflammasome models, USP3 knockdown Cellular & molecular immunology Medium 36050480
2022 USP3 inhibits HIV-1 replication by stabilizing APOBEC3G (A3G) through two mechanisms: (1) enzyme-activity-dependent deubiquitination of Vif-mediated polyubiquitination of A3G, blocking its proteasomal degradation; and (2) enzyme-activity-independent stabilization of A3G mRNA by directly binding to it. Immunoblotting, in vivo/in vitro deubiquitination assay, co-immunoprecipitation, immunofluorescence, RT-PCR, viral replication assays Chinese medical journal Medium 36574218
2023 USP3 deubiquitinates and stabilizes SIRT3 protein; PM2.5 decreases USP3 levels via the proteasome pathway, thereby reducing SIRT3, which in turn increases p53 acetylation at K320, driving pulmonary epithelial senescence and ferroptosis. Western blot, proteasome inhibitor experiments, USP3 knockdown/overexpression, SIRT3 activity assays, p53 acetylation assay Free radical biology & medicine Low 37348684
2023 USP3 deubiquitinates androgen receptor (AR), stabilizing it; this is mediated through a scaffold function of the lncRNA AC092894.1 that brings USP3 and AR together. Stabilized AR activates RASGRP3 transcription, sustaining MAPK signaling and sensitizing CRC cells to oxaliplatin-induced apoptosis. RNA pull-down, RIP, co-immunoprecipitation, ubiquitination assay, gain/loss-of-function experiments BMC medicine Medium 37013584
2023 USP3 interacts with and stabilizes REST by counteracting its ubiquitination-mediated degradation in neuroblastoma. USP3 loss reduces REST levels, promotes retinoic acid-induced neuronal differentiation, and attenuates neuroblastoma tumorigenesis in xenograft models. CRISPR-Cas9 genome-wide USP knockout screen, co-immunoprecipitation, Duolink proximity assay, in vitro deubiquitination assay, protein half-life assay, xenograft model Journal of experimental & clinical cancer research Medium 37170124
2024 USP3 directly interacts with SMARCA5 and removes K63-linked polyubiquitination from SMARCA5, maintaining its stability and promoting DNA damage repair and chemotherapy resistance in prostate cancer. Co-immunoprecipitation, K63-linkage specific ubiquitination assay, siRNA knockdown, overexpression rescue, in vivo xenograft Cell death & disease Medium 39500888
2024 USP3 binds to EPHA2 via its F2 domain (residues 159–520), with amino acid 203 critical for the interaction, and reduces EPHA2 ubiquitination to prevent its proteasomal degradation, thereby activating PI3K/AKT signaling in osteosarcoma. Co-immunoprecipitation, domain truncation mapping, ubiquitination assay, EPHA2 knockdown rescue experiment, western blot for PI3K/AKT pathway Cell death & disease Medium 38531846
2024 USP3 deubiquitinates ACOT7, preventing its ubiquitination-mediated degradation, thereby suppressing ferroptosis and promoting cisplatin resistance in NSCLC. Depletion of USP3 reduces ACOT7 expression, elevates iron/ROS/MDA, and sensitizes cells to cisplatin. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, ferroptosis markers (iron, ROS, MDA, GSH, GPX4, ACSL4), rescue experiment Anti-cancer drugs Low 38502867
2025 USP3 deubiquitinates DNM1L by cleaving K48-linked polyubiquitin chains, stabilizing DNM1L and promoting mitochondrial dysfunction, proliferation, and liver metastasis in gallbladder carcinoma. Co-immunoprecipitation, K48-linkage specific ubiquitination assay, xenograft and liver metastasis tumor models, electron microscopy, transcriptomics/metabolomics Biology direct Medium 40197257
2025 USP3 interacts with MYC and regulates MYC stability through deubiquitination in clear cell renal cell carcinoma, driving glycolysis; MYC overexpression partially reverses the metabolic effects of USP3 depletion. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, MYC overexpression rescue, glycolysis gene expression assays Biochimica et biophysica acta. General subjects Low 40164288
2025 RHBDL2 acts as a non-proteolytic scaffold stabilizing USP3 (via interaction anchored by RHBDL2 Val245), and stabilized USP3 in turn prevents proteasomal degradation of PPT1 through deubiquitination, fueling FASN-dependent de novo lipogenesis in osteosarcoma. Multi-omics, structural analysis, co-immunoprecipitation, ubiquitination assay, mutagenesis (RHBDL2 Val245), pharmacological inhibition (EGCG), in vivo xenograft Cell death & disease Medium 42031733
2025 Under hypoxic conditions, HIF-1α binds to the USP3 promoter and upregulates USP3 expression. USP3 then stabilizes MIC19 through K48-linked deubiquitination, maintaining mitochondrial function and promoting NSCLC progression. Chromatin immunoprecipitation (HIF-1α on USP3 promoter), co-immunoprecipitation, K48-linkage ubiquitination assay, USP3 knockdown/overexpression, xenograft model Acta pharmacologica Sinica Medium 40770539
2026 USP3 binds to PLK1, reduces K48-linked ubiquitination of PLK1, and stabilizes PLK1 protein levels, thereby promoting glioma cell proliferation, cell cycle progression, and invasion. Co-immunoprecipitation, western blotting for PLK1 ubiquitination (K48-linkage), USP3 knockdown/overexpression, xenograft model, cell cycle analysis Aging and disease Low 41525176
2026 USP3 binds to PD-L1 and inhibits its ubiquitination and proteasomal degradation, thereby stabilizing PD-L1 on NSCLC cells and contributing to immune escape. This is promoted upstream by EGFR-AS1/PCBP2 axis that enhances USP3 expression. Co-immunoprecipitation (PCBP2-USP3 and USP3-PD-L1), ubiquitination assay, PBMC co-culture cytotoxicity assay, siRNA knockdown Biological procedures online Low 41957704

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Human USP3 is a chromatin modifier required for S phase progression and genome stability. Current biology : CB 246 17980597
2013 USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors. Cell research 152 24366338
2013 USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15. Cell cycle (Georgetown, Tex.) 101 24196443
2014 Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells. The Journal of experimental medicine 66 25113974
2021 An ALYREF-MYCN coactivator complex drives neuroblastoma tumorigenesis through effects on USP3 and MYCN stability. Nature communications 65 33767157
2023 PM2.5 contributed to pulmonary epithelial senescence and ferroptosis by regulating USP3-SIRT3-P53 axis. Free radical biology & medicine 59 37348684
2019 USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5. The Journal of biological chemistry 56 31624151
2019 Universal Solid-Phase Protein Preparation (USP3) for Bottom-up and Top-down Proteomics. Journal of proteome research 49 31137935
2020 Smoothened Promotes Glioblastoma Radiation Resistance Via Activating USP3-Mediated Claspin Deubiquitination. Clinical cancer research : an official journal of the American Association for Cancer Research 44 31900278
2020 Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer. Cell death and differentiation 43 32415280
2021 USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation. Cell death & disease 41 34930901
2020 LncRNA HOXA-AS3 promotes the malignancy of glioblastoma through regulating miR-455-5p/USP3 axis. Journal of cellular and molecular medicine 39 32918360
2017 Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer. Scientific reports 36 28655924
2020 Hsa_circ_0017639 expression promotes gastric cancer proliferation and metastasis by sponging miR-224-5p and upregulating USP3. Gene 32 32376451
2018 Deubiquitinating enzyme USP3 controls CHK1 chromatin association and activation. Proceedings of the National Academy of Sciences of the United States of America 30 29735693
2024 USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway. Cell death & disease 28 38531846
2023 Downregulation of AC092894.1 promotes oxaliplatin resistance in colorectal cancer via the USP3/AR/RASGRP3 axis. BMC medicine 28 37013584
1999 Characterization and chromosomal localization of USP3, a novel human ubiquitin-specific protease. The Journal of biological chemistry 28 10480896
2017 USP3 stabilizes p53 protein through its deubiquitinase activity. Biochemical and biophysical research communications 23 28807825
2022 USP3 deubiquitinates and stabilizes the adapter protein ASC to regulate inflammasome activation. Cellular & molecular immunology 22 36050480
2021 Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma. BMC cancer 22 34758762
2020 USP3 promotes proliferation of non-small cell lung cancer through regulating RBM4. European review for medical and pharmacological sciences 21 32271432
2021 MicroRNA-146-5p Promotes Pulmonary Artery Endothelial Cell Proliferation under Hypoxic Conditions through Regulating USP3. Disease markers 14 34917199
2024 USP3 promotes DNA damage response and chemotherapy resistance through stabilizing and deubiquitinating SMARCA5 in prostate cancer. Cell death & disease 13 39500888
2023 CRISPR/Cas9-based genome-wide screening of the deubiquitinase subfamily identifies USP3 as a protein stabilizer of REST blocking neuronal differentiation and promotes neuroblastoma tumorigenesis. Journal of experimental & clinical cancer research : CR 13 37170124
2024 USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis. Anti-cancer drugs 12 38502867
2025 Organoid modeling identifies USP3-AS1 as a novel promoter in colorectal cancer liver metastasis through increasing glucose-driven histone lactylation. Acta pharmacologica Sinica 7 39837984
2024 USP3: Key deubiquitylation enzyme in human diseases. Cancer science 7 38651282
2021 Upregulation of circular and linear METTL3 and USP3 in colorectal cancer. Oncology letters 7 34345300
2016 Quantitative analysis by next generation sequencing of hematopoietic stem and progenitor cells (LSK) and of splenic B cells transcriptomes from wild-type and Usp3-knockout mice. Data in brief 7 26909367
2022 Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners. Chinese medical journal 6 36574218
2024 USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent Growth via Suppressing Wnt/β-catenin. Current molecular medicine 5 37921189
2025 Deubiquitination of DNM1L by USP3 triggers the development and metastasis of gallbladder carcinoma. Biology direct 2 40197257
2025 USP3 promotes clear cell renal cell carcinoma progression by stabilizing MYC and enhancing glycolysis. Biochimica et biophysica acta. General subjects 1 40164288
2026 USP3 Promotes Glioma Progression by Stabilizing PLK1 through Deubiquitination. Aging and disease 0 41525176
2026 Mechanism of RBM15 in the Immune Escape of Non-small Cell Lung Cancer Cells Via the LncRNA EGFR-AS1/USP3/PD-L1 Axis. Biological procedures online 0 41957704
2026 RHBDL2 drives lipid metabolic reprogramming in osteosarcoma via USP3-mediated deubiquitination of PPT1. Cell death & disease 0 42031733
2025 Vitamin B12 as a novel USP3 deubiquitinase inhibitor suppresses cell proliferation and growth in osteosarcoma. Biochemical and biophysical research communications 0 40179740
2025 USP3 stabilizes MIC19 by deubiquitination under hypoxic stress and promotes the progression of non-small cell lung cancer. Acta pharmacologica Sinica 0 40770539

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