Affinage

USP3

Ubiquitin carboxyl-terminal hydrolase 3 · UniProt Q9Y6I4

Length
520 aa
Mass
58.9 kDa
Annotated
2026-04-28
38 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP3 is a ubiquitin-specific protease that removes K48- and K63-linked ubiquitin chains from a broad range of nuclear and cytoplasmic substrates, functioning as a central regulator of the DNA damage response, cell cycle progression, innate immune signaling, and inflammasome activation. Its ZnF-UBP domain mediates engagement with ubiquitinated substrates, as first demonstrated for monoubiquitinated histones H2A and H2B, where USP3 counteracts RNF168/RNF8-dependent ubiquitination at H2A K13/K15 to modulate recruitment of repair factors BRCA1 and 53BP1 (PMID:17980597, PMID:24196443). Genetic deletion in mice causes increased histone ubiquitination, chromosomal instability, hematopoietic stem cell exhaustion, and spontaneous tumorigenesis, establishing USP3 as essential for genome maintenance in vivo (PMID:25113974). Beyond histones, USP3 deubiquitinates CHK1 at K132 to simultaneously release it from chromatin and activate its kinase domain (PMID:29735693), removes K63-linked chains from RIG-I to suppress type I interferon signaling (PMID:24366338), stabilizes the inflammasome adaptor ASC by removing K48-linked chains (PMID:36050480), and deubiquitinates numerous additional substrates including KLF5, Cdc25A, p53, REST, SMARCA5, and EPHA2 to regulate proliferation and therapy resistance in diverse cancer contexts (PMID:31624151, PMID:32415280, PMID:37170124).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Establishing that USP3 possesses intrinsic deubiquitinating activity answered whether the gene encodes a functional protease, providing the enzymatic foundation for all subsequent substrate studies.

    Evidence In vitro cleavage of ubiquitin-proline bonds and yeast complementation assays

    PMID:10480896

    Open questions at the time
    • No endogenous mammalian substrate identified
    • No structural information on the catalytic domain
    • Chain-type specificity not addressed
  2. 2007 High

    Identifying histones H2A and H2B as physiological substrates and demonstrating that the ZnF-UBP domain mediates substrate engagement established USP3 as a chromatin-associated deubiquitinase required for S-phase integrity and DNA damage resolution.

    Evidence RNAi knockdown, chromatin fractionation, live-cell imaging, γH2AX foci quantification, ZnF-UBP domain mapping in human cells

    PMID:17980597

    Open questions at the time
    • Specific lysine residues on H2A/H2B not mapped
    • Epistatic relationship with ubiquitin ligases not defined
    • In vivo organismal phenotype unknown
  3. 2013 High

    Mapping the precise H2A/H2AX lysine targets (K13/K15 and K118/K119) and showing that USP3 counteracts RNF168/RNF8 signaling placed USP3 within the well-defined ubiquitin cascade governing DNA repair factor recruitment.

    Evidence Site-specific H2A/H2AX lysine mutagenesis, immunofluorescence for FK2 and 53BP1/BRCA1 foci

    PMID:24196443

    Open questions at the time
    • Whether USP3 directly competes with RNF168 at chromatin not tested
    • Structural basis of K13/K15 selectivity unknown
  4. 2013 High

    Demonstrating that USP3 removes K63-linked chains from RIG-I to suppress type I interferon production expanded its function beyond chromatin to cytoplasmic innate immune signaling.

    Evidence Co-IP with RIG-I CARD domain, in vitro K63-chain cleavage, RNAi-enhanced IFN production, antiviral assays

    PMID:24366338

    Open questions at the time
    • Whether USP3 regulates additional pattern recognition receptors beyond RLRs not fully explored
    • In vivo immune phenotype not tested in knockout mice
  5. 2014 High

    The Usp3-knockout mouse provided in vivo proof that USP3-mediated histone deubiquitination is essential for genome stability, hematopoietic stem cell homeostasis, and tumor suppression.

    Evidence Usp3Δ/Δ mice with HSC transplantation, flow cytometry, chromosomal integrity assays, and spontaneous tumor monitoring

    PMID:25113974

    Open questions at the time
    • Which USP3 substrates (histone vs. non-histone) drive the HSC and tumor phenotypes not dissected
    • Tissue-specific conditional knockouts not reported
  6. 2017 Medium

    Identification of p53 as a USP3 substrate linked USP3 catalytic activity to stabilization of a major tumor suppressor, suggesting context-dependent oncogenic or tumor-suppressive roles.

    Evidence Co-IP, deubiquitination assay with catalytically dead C168S mutant, proliferation/transformation assays

    PMID:28807825

    Open questions at the time
    • Specific ubiquitin chain type on p53 not identified
    • In vivo relevance of USP3-p53 axis not validated in mouse models
    • No in vitro reconstitution with purified proteins
  7. 2018 High

    Showing that USP3 removes K63-linked ubiquitin from CHK1 K132 to simultaneously release CHK1 from chromatin and open its active site revealed a dual-regulatory mechanism coupling substrate deubiquitination to kinase activation in the DNA damage checkpoint.

    Evidence Site-specific K132 mutagenesis, NLS-mutant USP3, chromatin fractionation, CHK1 kinase assays

    PMID:29735693

    Open questions at the time
    • Identity of the E3 ligase attaching K63 chains to CHK1 K132 not established
    • Temporal dynamics of USP3-CHK1 interaction during checkpoint activation unknown
  8. 2019 High

    Genome-wide siRNA screening identified KLF5 as a USP3 substrate, linking USP3 deubiquitinase activity to breast cancer cell proliferation and in vivo tumorigenesis.

    Evidence Genome-wide siRNA screen, Co-IP, deubiquitination assay, KLF5 rescue in xenograft model

    PMID:31624151

    Open questions at the time
    • Chain type specificity on KLF5 not defined
    • Relationship between KLF5 stabilization and USP3's histone function not explored
  9. 2020 High

    CRISPR-based genome-scale screening independently validated USP3 as a Cdc25A stabilizer, establishing a second cell-cycle control axis and confirming USP3's role in cervical tumor growth.

    Evidence CRISPR/Cas9 genome-scale USP knockout screen, cell-cycle analysis, cervical cancer xenograft model

    PMID:32415280

    Open questions at the time
    • Direct deubiquitination site on Cdc25A not mapped
    • Interplay between Cdc25A and CHK1 regulation by USP3 not addressed
  10. 2020 Medium

    Discovery that Smo transcriptionally upregulates USP3 to stabilize Claspin and sustain ATR-Chk1 signaling connected USP3 to radiation resistance in glioblastoma through a Hedgehog-USP3-Claspin axis.

    Evidence USP3 overexpression/knockdown, Claspin Co-IP, ubiquitination assays, GBM xenograft radioresistance model

    PMID:31900278

    Open questions at the time
    • Direct binding interface between USP3 and Claspin not mapped
    • Whether this axis operates outside GBM unknown
  11. 2021 Medium

    Identification of Aurora A K143 as a deubiquitination site and COL9A3/COL6A5 as proteomics-identified substrates broadened USP3's substrate repertoire to kinases and extracellular matrix proteins in distinct cancer types.

    Evidence Site-specific Aurora A K143R mutagenesis and Co-IP (ESCC); iTRAQ proteomics with Co-IP (gastric cancer)

    PMID:34758762 PMID:34930901

    Open questions at the time
    • In vitro reconstitution with purified USP3 and Aurora A not performed
    • Physiological relevance of collagen deubiquitination unclear
  12. 2022 Medium

    Demonstrating K48-linked deubiquitination of inflammasome adaptor ASC established USP3 as a positive regulator of inflammasome activation, extending its immune function beyond the RIG-I pathway.

    Evidence In vitro/in vivo deubiquitination assays, mouse peritonitis, F. novicida infection, and flagellin-induced pneumonia models

    PMID:36050480

    Open questions at the time
    • Which inflammasome(s) are most dependent on USP3 in vivo not systematically compared
    • Relationship to USP3-null mouse immune phenotype not explored
  13. 2022 Medium

    USP3 was shown to stabilize APOBEC3G both by deubiquitinating Vif-mediated K48-linked chains and by an enzyme-activity-independent mRNA-stabilizing function, revealing a non-catalytic role in antiviral defense.

    Evidence Co-IP, in vitro deubiquitination, mRNA stability assays, HIV-1 replication assays

    PMID:36574218

    Open questions at the time
    • RNA-binding domain or motif responsible for mRNA stabilization not identified
    • In vivo HIV model not tested
  14. 2023 Medium

    CRISPR screening identified REST as a USP3 substrate in neuroblastoma, connecting USP3-dependent protein stabilization to blockade of retinoic acid-induced neuronal differentiation.

    Evidence CRISPR/Cas9 genome-scale knockout screen, Duolink proximity assay, in vitro deubiquitination, xenograft models

    PMID:37170124

    Open questions at the time
    • Whether USP3 regulation of REST is specific to neuroblastoma or general not tested
    • Ubiquitin chain type on REST not defined
  15. 2024 Medium

    Domain mapping of the USP3-EPHA2 interaction (residues 159–520, with residue 203 critical) provided the first detailed binding-region analysis for a non-histone substrate, linking USP3 to PI3K/AKT activation in osteosarcoma.

    Evidence Truncation/domain mutant analysis, Co-IP, ubiquitination assay, PI3K/AKT readouts

    PMID:38531846

    Open questions at the time
    • No crystal structure of USP3 bound to any substrate
    • Whether residue 203 is a general substrate-docking determinant is unknown
  16. 2025 Medium

    Identification of DNM1L and MIC19 as USP3 substrates connected USP3 to mitochondrial dynamics and function, revealing roles in hepatic metastasis and hypoxia-driven NSCLC progression.

    Evidence Co-IP and ubiquitination assays for DNM1L (gallbladder carcinoma xenograft) and MIC19 (ChIP showing HIF-1α drives USP3 expression; NSCLC xenograft)

    PMID:40197257 PMID:40770539

    Open questions at the time
    • Direct in vitro reconstitution of USP3 with DNM1L or MIC19 not shown
    • Whether mitochondrial substrates are accessed in the nucleus or cytoplasm unclear
  17. 2026 Medium

    Discovery that RHBDL2 stabilizes USP3 protein via a non-proteolytic scaffold mechanism, and that stabilized USP3 deubiquitinates PPT1 to promote de novo lipogenesis, revealed an upstream regulatory layer controlling USP3 abundance.

    Evidence Multi-omics, structural analysis of RHBDL2 Val245 interface, Co-IP, lipid metabolomics, osteosarcoma xenograft

    PMID:42031733

    Open questions at the time
    • Generality of RHBDL2-USP3 stabilization beyond osteosarcoma unknown
    • How USP3 protein turnover is regulated in normal tissues not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A structural basis for USP3's broad substrate selectivity, the rules governing its deployment to K48- vs. K63-linked chains on different substrates, and the relative contributions of histone vs. non-histone deubiquitination to its tumor-suppressive versus tumor-promoting activities in vivo remain unresolved.
  • No crystal or cryo-EM structure of USP3 alone or with substrates
  • Substrate selectivity determinants (beyond ZnF-UBP) undefined
  • Conditional tissue-specific knockout studies separating histone from non-histone functions not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016787 hydrolase activity 4 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2
Partners
ASCCDC25ACHEK1H2AH2BKLF5RIG-ISMARCA5

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 USP3 is a deubiquitinating enzyme for monoubiquitinated histone H2A (uH2A) and H2B (uH2B); the ZnF-UBP domain of USP3 mediates its interaction with uH2A. USP3 dynamically associates with chromatin and deubiquitinates H2A/H2B in vivo. Functional ablation by RNAi causes S phase delay, accumulation of DNA breaks, and activation of DNA damage checkpoints. USP3 is also required for full deubiquitination of ubiquitin-conjugates/uH2A and γH2AX dephosphorylation following ionizing radiation. RNAi knockdown, in vivo deubiquitination assays, chromatin fractionation, live-cell imaging, domain mapping (ZnF-UBP), γH2AX foci analysis Current biology : CB High 17980597
1999 USP3 is a functional ubiquitin-specific protease in vitro, capable of cleaving ubiquitin from substrates including a ubiquitin-proline bond, and can inhibit ubiquitin-dependent degradation of both an N-end rule substrate and abnormal endogenous proteins in yeast. In vitro deubiquitination assay, yeast functional complementation assay The Journal of biological chemistry High 10480896
2013 USP3 negatively regulates type I interferon signaling by deubiquitinating K63-linked polyubiquitin chains from RIG-I (and other RLRs). Upon viral infection or ligand stimulation, USP3 binds the CARD domain of RLRs and cleaves polyubiquitin chains via cooperation of its zinc-finger Ub-binding domain and USP catalytic domain. Binding of USP3 to polyubiquitin chains on RIG-I is a prerequisite for cleavage. USP3 knockdown enhanced K63-linked ubiquitination of RIG-I, IRF3 phosphorylation, and type I interferon production. Co-IP, RNAi knockdown, in vivo/in vitro deubiquitination assay, mutation analysis, antiviral assays Cell research High 24366338
2013 USP3 deubiquitinates H2A and γH2AX specifically at lysine 13 and 15 (initiated by RNF168) and also at lysine 118 and 119 of H2AX in response to DNA damage. USP3 overexpression abrogated ubiquitin-conjugate foci and impaired recruitment of downstream repair factors BRCA1 and 53BP1 to damage sites, placing USP3 as a counterregulator of RNF168/RNF8-mediated ubiquitination signaling. Ectopic expression, site-specific mutagenesis of H2A/H2AX lysine residues, immunofluorescence (FK2 foci, γH2AX), immunoprecipitation Cell cycle (Georgetown, Tex.) High 24196443
2014 USP3 deletion in mice (Usp3Δ/Δ) increases levels of histone ubiquitination in adult tissues, reduces hematopoietic stem cell (HSC) reserves over time, impairs HSC self-renewal and repopulation potential, and leads to spontaneous tumor development and chromosomal instability, demonstrating that USP3-mediated histone H2A deubiquitination is required for genome maintenance and HSC homeostasis in vivo. Knockout mouse model, hematopoietic stem cell transplantation assays, flow cytometry, γH2AX analysis, chromosomal integrity assays The Journal of experimental medicine High 25113974
2018 USP3 removes K63-linked ubiquitin chains from CHK1 at residue K132 (at the kinase active site). This K63-linked ubiquitin chain normally promotes CHK1 nuclear localization and chromatin association but inhibits kinase activity. USP3 (wild-type but not catalytically defective or NLS-deficient mutants) reduces CHK1 K63-linked ubiquitination, releases CHK1 from chromatin, and simultaneously opens the active site to increase substrate accessibility — dual roles in CHK1 regulation post-DNA damage. In vivo ubiquitination assay, catalytic mutant analysis, NLS-mutant analysis, CHK1 chromatin fractionation, kinase activity assays, RNAi knockdown Proceedings of the National Academy of Sciences of the United States of America High 29735693
2019 USP3 interacts with and stabilizes the KLF5 transcription factor via deubiquitination, identified by genome-wide siRNA library screening. USP3 knockdown inhibits breast cancer cell proliferation in vitro and tumorigenesis in vivo, effects partially rescued by ectopic KLF5 expression. Genome-wide siRNA screen, Co-IP, in vivo/in vitro deubiquitination assay, rescue experiment, xenograft model The Journal of biological chemistry High 31624151
2020 USP3 was identified by CRISPR/Cas9 genome-scale USP knockout screening as a deubiquitinase that stabilizes Cdc25A. USP3 depletion reduces Cdc25A protein levels and causes significant delay in cell-cycle progression, reducing cervical tumor xenograft growth. CRISPR/Cas9 genome-scale knockout screen, Western blot, cell-cycle analysis, xenograft model Cell death and differentiation High 32415280
2020 Smoothened (Smo) promotes GBM radiation resistance by transcriptionally upregulating USP3, which then deubiquitinates and stabilizes Claspin, preventing its polyubiquitination and proteasomal degradation, thereby sustaining ATR-Chk1 signaling. In vitro and in vivo radioresistance assays, USP3 overexpression/knockdown, Co-IP for Claspin-USP3 interaction, ubiquitination assay, xenograft model Clinical cancer research Medium 31900278
2017 USP3 interacts with p53 and stabilizes p53 protein through its deubiquitinase activity; reconstitution of wild-type but not catalytically inactive USP3 C168S mutant restores p53 stability, inhibiting cell proliferation and transformation. Co-IP, deubiquitination assay, catalytic mutant (C168S), proliferation and transformation assays Biochemical and biophysical research communications Medium 28807825
2021 USP3 interacts with and stabilizes COL9A3 and COL6A5 via deubiquitination in gastric cancer cells, promoting tumor progression and metastasis. These substrates were identified by isobaric tags for relative and absolute quantification (iTRAQ) proteomics. iTRAQ proteomics, Co-IP, in vivo/in vitro deubiquitination assay, in vitro and in vivo functional assays Cell death & disease Medium 34930901
2021 USP3 suppresses Aurora A ubiquitination at K143, reducing its proteasomal degradation and stabilizing the kinase in esophageal squamous cell carcinoma cells. The deubiquitination-resistant Aurora A K143R mutant has enhanced kinase activity and is not regulated by USP3. Co-IP, ubiquitination assay, site-specific mutagenesis (Aurora A K143R), proliferation and invasion assays BMC cancer Medium 34758762
2022 USP3 directly deubiquitinates ASC (the inflammasome adapter), removing K48-linked ubiquitination and blocking its proteasomal degradation. USP3 promotes inflammasome activation in mouse models of peritonitis, F. novicida infection, and flagellin-induced pneumonia. Co-IP, in vitro/in vivo deubiquitination assay, inflammasome activation assays, mouse infection models Cellular & molecular immunology Medium 36050480
2021 The ALYREF-MYCN coactivator complex stimulates transcription of USP3. Increased USP3 levels reduce K48- and K63-linked ubiquitination of MYCN, driving up MYCN protein stability in neuroblastoma. Transgenic neuroblastoma models, Co-IP, ubiquitination assay, transcription reporter assays Nature communications Medium 33767157
2023 USP3 deubiquitinates SIRT3, preventing its proteasomal degradation. PM2.5 downregulates USP3, leading to reduced SIRT3 protein levels. SIRT3 in turn deacetylates p53 at K320 to suppress its transcriptional activity, placing USP3 upstream of the SIRT3-p53 axis in pulmonary epithelial senescence and ferroptosis. Western blot, genetic depletion, adenoviral overexpression, proteasome inhibitor experiments, deacetylation assay Free radical biology & medicine Medium 37348684
2024 USP3 directly interacts with EPHA2 via its USP3-F2 domain (residues 159-520, with amino acid 203 critical), reduces EPHA2 polyubiquitination and proteasomal degradation, and activates the PI3K/AKT signaling pathway in osteosarcoma. Co-IP, truncation/domain mutant analysis, ubiquitination assay, PI3K/AKT pathway readout, rescue experiments with EPHA2 knockdown Cell death & disease Medium 38531846
2023 USP3 was identified by CRISPR/Cas9 genome-scale USP knockout screening as a deubiquitinase that stabilizes REST (repressor element-1 silencing transcription factor) in neuroblastoma. USP3 interacts with REST, removes its ubiquitination, extends its half-life, blocks retinoic acid-induced neuronal differentiation, and promotes neuroblastoma tumorigenesis in xenograft models. CRISPR/Cas9 genome-scale knockout screen, Co-IP, Duolink proximity assay, in vitro deubiquitination assay, protein half-life assay, xenograft model Journal of experimental & clinical cancer research : CR Medium 37170124
2024 USP3 directly interacts with SMARCA5 and removes K63-linked polyubiquitination of SMARCA5 to maintain its stability, promoting DNA damage repair and chemotherapy resistance in prostate cancer. Depletion of USP3 or SMARCA5 sensitizes cells to docetaxel; USP3 overexpression restores resistance in SMARCA5-silenced cells. Co-IP, in vitro/in vivo deubiquitination assay, rescue experiments, xenograft model Cell death & disease Medium 39500888
2022 USP3 stabilizes APOBEC3G (A3G) by deubiquitinating Vif-mediated K48-linked polyubiquitination on A3G, blocking its proteasomal degradation. Additionally, USP3 stabilizes A3G mRNA in an enzyme-activity-independent manner by binding to the mRNA, thereby inhibiting HIV-1 replication. Co-IP, in vivo/in vitro deubiquitination assay, immunofluorescence, co-localization, mRNA stability assay, HIV replication assay Chinese medical journal Medium 36574218
2024 USP3 deubiquitinates ACOT7 and upregulates its protein expression, thereby suppressing ferroptosis in NSCLC cells and promoting cisplatin resistance. USP3 and ACOT7 interact as shown by Co-IP. Co-IP, ubiquitination assay, ferroptosis markers (ROS, MDA, GSH, GPX4, ACSL4, iron), rescue experiments Anti-cancer drugs Medium 38502867
2023 AC092894.1 lncRNA acts as a scaffold that mediates deubiquitination of the androgen receptor (AR) through USP3, increasing AR stability and transcriptional activity of RASGRP3, thereby activating MAPK signaling in colorectal cancer. RNA pulldown, RIP, Co-IP, gain/loss-of-function experiments BMC medicine Low 37013584
2025 USP3 directly interacts with DNM1L and cleaves K48-linked polyubiquitin chains to deubiquitinate and stabilize DNM1L, promoting mitochondrial dysfunction, proliferation, invasiveness, and hepatic metastasis of gallbladder carcinoma. Co-IP, ubiquitination assay, xenograft and liver metastasis models, transmission electron microscopy, MitoTracker staining Biology direct Medium 40197257
2025 USP3 stabilizes MIC19 through K48-linked deubiquitination under hypoxic conditions. HIF-1α binds the USP3 promoter to promote USP3 expression, which in turn deubiquitinates and stabilizes MIC19, maintaining mitochondrial function and driving NSCLC progression. Western blot, Co-IP, ubiquitination assay, ChIP (HIF-1α on USP3 promoter), xenograft model Acta pharmacologica Sinica Medium 40770539
2025 USP3 interacts with MYC by Co-IP and regulates MYC stability through deubiquitination, promoting ccRCC progression and glycolysis. MYC overexpression partially reverses effects of USP3 depletion on glycolysis-related gene expression. Co-IP, ubiquitination assay, functional rescue experiments Biochimica et biophysica acta. General subjects Low 40164288
2026 USP3 interacts with PLK1, reduces K48-linked ubiquitination of PLK1, and stabilizes PLK1 protein levels, thereby promoting glioma cell proliferation, cell cycle progression, and invasion. Co-IP, Western blot, ubiquitination assay, xenograft model, flow cytometry Aging and disease Low 41525176
2026 RHBDL2 acts as a non-proteolytic scaffold to stabilize USP3 (via a hydrophobic interface anchored by RHBDL2 Val245, independent of RHBDL2 protease activity). Stabilized USP3 then deubiquitinates PPT1 to prevent its proteasomal degradation, promoting FASN-dependent de novo lipogenesis and osteosarcoma malignancy. Multi-omics, structural analysis, Co-IP, ubiquitination assay, lipid metabolomics, xenograft model, pharmacological disruption of RHBDL2-USP3 interface Cell death & disease Medium 42031733

Source papers

Stage 0 corpus · 38 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 151 24366338
2013 USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15. Cell cycle (Georgetown, Tex.) 99 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 64 33767157
2023 PM2.5 contributed to pulmonary epithelial senescence and ferroptosis by regulating USP3-SIRT3-P53 axis. Free radical biology & medicine 57 37348684
2019 USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5. The Journal of biological chemistry 55 31624151
2019 Universal Solid-Phase Protein Preparation (USP3) for Bottom-up and Top-down Proteomics. Journal of proteome research 47 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 43 31900278
2020 Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer. Cell death and differentiation 42 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
1999 Characterization and chromosomal localization of USP3, a novel human ubiquitin-specific protease. The Journal of biological chemistry 28 10480896
2024 USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway. Cell death & disease 27 38531846
2023 Downregulation of AC092894.1 promotes oxaliplatin resistance in colorectal cancer via the USP3/AR/RASGRP3 axis. BMC medicine 27 37013584
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
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 11 38502867
2024 USP3 promotes DNA damage response and chemotherapy resistance through stabilizing and deubiquitinating SMARCA5 in prostate cancer. Cell death & disease 10 39500888
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
2025 Organoid modeling identifies USP3-AS1 as a novel promoter in colorectal cancer liver metastasis through increasing glucose-driven histone lactylation. Acta pharmacologica Sinica 5 39837984
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 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