Affinage

USP7

Ubiquitin carboxyl-terminal hydrolase 7 · UniProt Q93009

Length
1102 aa
Mass
128.3 kDa
Annotated
2026-06-11
100 papers in source corpus 58 papers cited in narrative 59 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

USP7 (HAUSP) is a cysteine deubiquitinase that acts as a central hub for protein-stability control, removing predominantly K48-linked polyubiquitin chains from a broad substrate network to oppose proteasomal degradation (PMID:15053880, PMID:29045385). It is a monomeric, multidomain enzyme: an N-terminal TRAF-like domain recognizes substrates through a short P/AXXS motif (Trp165 critical), as defined by co-crystal structures with p53 and MDM2 peptides, while the catalytic activity is allosterically activated ~100-fold by the C-terminal di-Ubl unit (HUBL-45) engaging a 'switching' loop in the catalytic domain and is further hyperactivated by the metabolic enzyme GMPS (PMID:16474402, PMID:21981925, PMID:14506283). Its founding and best-defined role is in the p53–MDM2 axis, where USP7 deubiquitinates and stabilizes both p53 and MDM2/MDMX, and its dosage determines whether it preferentially protects MDM2 (repressing p53) or p53 itself (PMID:15053880, PMID:15916963); consistent with this, Hausp-null mice die in early embryogenesis with p53 activation that is only partially relieved by p53 deletion, revealing additional essential p53-independent functions (PMID:19946331). USP7 activity is itself tuned by post-translational control — CK2-mediated Ser18 phosphorylation stabilizes the enzyme in unstressed cells, while ATM-dependent PPM1G dephosphorylation downregulates it after DNA damage to permit p53 accumulation, and Trip12 ubiquitinates USP7 to limit its abundance (PMID:22361354, PMID:27800609). Beyond p53, USP7 stabilizes substrates across the DNA damage response and replication (Chk1, Rad18, MCM-BP-dependent MCM unloading) (PMID:25483066, PMID:25961918, PMID:24190967), developmental and growth signaling (Ci/Gli in Hedgehog, YAP/TAZ in Hippo, N-Myc) (PMID:27618649, PMID:26120032, PMID:30679505), and numerous oncoproteins including KRAS, BCR-ABL, and NOTCH1 (PMID:30370059, PMID:39499616, PMID:33963175). USP7 also restrains polyglutamine-disease proteostasis, where it preferentially deubiquitinates polyQ-expanded androgen receptor to promote aggregation, and its inhibition ameliorates SBMA and ALS phenotypes in vivo (PMID:33170804, PMID:33106424). A reported USP7–DNMT1 stabilization model was not supported by genetic testing, as DNMT1 levels are normal in USP7-null cells (PMID:29482658).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2003 High

    Establishing USP7 as a modular, catalytically active deubiquitinase set the structural framework for all later substrate work, defining an N-terminal substrate-binding domain distinct from the C-terminal regulatory region.

    Evidence Partial proteolysis/MS domain mapping, fluorescence binding, and in vitro deubiquitinase assays on purified protein

    PMID:14506283

    Open questions at the time
    • Did not resolve how the C-terminal domains regulate catalysis
    • Substrate-recognition motif not yet defined
  2. 2004 High

    Defining USP7's dose-dependent, opposing effects on p53 and MDM2 explained how one deubiquitinase can either repress or activate the p53 pathway, answering how USP7 sits at the center of this circuit.

    Evidence Graded RNAi knockdown, Co-IP, and in vivo ubiquitination assays across cell lines

    PMID:15053880

    Open questions at the time
    • Did not establish what shifts substrate preference between MDM2 and p53
    • Structural basis of binding not yet known
  3. 2006 High

    Co-crystal structures defined the P/AXXS recognition motif and the shared TRAF-domain surface used by p53, MDM2 and EBNA1, providing the molecular logic for competitive substrate selection.

    Evidence X-ray co-crystal structures of the N-terminal domain with p53/MDM2 peptides plus mutagenesis

    PMID:16474402

    Open questions at the time
    • Did not explain how a trimeric p53-MDM2-USP7 state forms given mutually exclusive binding
    • Affinity ranking of full substrate repertoire unknown
  4. 2005 High

    Extending USP7 substrates to MDMX/HDMX and linking ATM phosphorylation to reduced USP7 affinity connected the enzyme to DNA-damage-regulated control of the p53 axis.

    Evidence Co-IP, in vivo/in vitro deubiquitination, RNAi, and DNA damage treatments

    PMID:15916963

    Open questions at the time
    • Direct phosphatase/kinase controlling USP7 itself not yet identified
    • Quantitative contribution to DDR not resolved
  5. 2006 High

    Demonstrating non-degradative deubiquitination of FOXO4 showed USP7 can reverse mono-ubiquitination to control localization and transcription without altering protein half-life, broadening its functional output beyond stabilization.

    Evidence Reciprocal Co-IP, deubiquitination assays, localization imaging, transcriptional reporters

    PMID:16964248

    Open questions at the time
    • Chain-type specificity of FOXO4 mono-Ub removal not defined
    • Recruitment mechanism to FOXO4 not mapped
  6. 2008 High

    Placing USP7 within a PML-DAXX network controlling PTEN nuclear-cytoplasmic trafficking established that USP7 regulates substrate localization through deubiquitination, integrating it into tumor-suppressor compartmentalization.

    Evidence Co-IP, deubiquitination assays, nuclear fractionation, RNAi, rescue experiments

    PMID:18716620

    Open questions at the time
    • Direct vs DAXX-mediated effect on PTEN not fully separated
    • Chain linkage on PTEN not characterized
  7. 2009 High

    Knockout mice resolved the in vivo essentiality of USP7, showing early lethality driven by p53 activation but only partly rescued by p53 loss, proving p53-independent essential functions exist.

    Evidence Conventional/conditional knockout mice with hausp/p53 double-knockout epistasis

    PMID:19946331

    Open questions at the time
    • Identity of the p53-independent essential substrates not defined
    • Tissue-specific requirements not dissected
  8. 2011 High

    The crystal structure of the C-terminal Ubl array explained how USP7 is allosterically switched on, showing HUBL-45 activates the catalytic domain ~100-fold and GMPS stabilizes this active state.

    Evidence Crystal structure of C-terminal Ubl domains, in vitro activity assays, domain mutagenesis

    PMID:21981925

    Open questions at the time
    • How substrate binding couples to the switching loop in cells not resolved
    • Regulation of GMPS recruitment unknown
  9. 2012 High

    Identifying CK2 (writer) and PPM1G (eraser) acting on Ser18 defined the phospho-switch that links DNA damage to USP7 abundance and p53 derepression, answering how USP7 itself is regulated by stress.

    Evidence Phospho-mapping, kinase/phosphatase assays, RNAi, IR treatment, Western blotting

    PMID:22361354

    Open questions at the time
    • Quantitative effect of Ser18 on catalysis vs stability not fully separated
    • Isoform-specific regulation incompletely defined
  10. 2016 Medium

    Defining Trip12 as the E3 ligase for USP7 closed the loop on USP7's own turnover and linked its degradation to DDR substrate stability (p53, 53BP1, Chk1).

    Evidence Co-IP, in vivo ubiquitination, RNAi, cell cycle analysis

    PMID:27800609

    Open questions at the time
    • Single-lab finding without in vitro reconstitution
    • Chain type used by Trip12 on USP7 not defined
  11. 2015 High

    A cluster of studies extended USP7 deubiquitination into the DNA replication and damage-tolerance machinery (Chk1, Rad18, MCM-BP), establishing USP7 as a stabilizer of replication and checkpoint factors via the P/AXXS-type motif.

    Evidence Co-IP, in vitro/in vivo deubiquitination, RNAi, UV/PCNA ubiquitination, chromatin fractionation, replication assays

    PMID:24190967 PMID:25483066 PMID:25961918

    Open questions at the time
    • Relative contribution of each substrate to genome stability not ranked
    • How USP7 timing on MCM unloading is controlled unclear
  12. 2015 High

    Cross-species work placed USP7 in developmental signaling, showing it stabilizes Ci/Gli (Hedgehog) and Yorkie/YAP-TAZ (Hippo) and that pathway activation modulates USP7-substrate binding.

    Evidence Co-IP, in vivo ubiquitination, Drosophila genetics, mammalian cell assays

    PMID:26120032 PMID:30679505

    Open questions at the time
    • Direct deubiquitination chain specificity on Gli/YAP not fully resolved
    • Signal-dependent regulation of binding mechanistically undefined
  13. 2016 High

    Identification of N-Myc as a USP7 substrate with in vivo knockout validation established USP7 as a stabilizer of an oncogenic transcription factor and a therapeutic target in neuroblastoma.

    Evidence Co-IP, deubiquitination assays, RNAi, conditional knockout mice, xenografts, USP7 inhibitors

    PMID:27618649

    Open questions at the time
    • Whether N-Myc stabilization is direct vs cofactor-dependent not fully separated
    • Selectivity over c-Myc not addressed
  14. 2017 High

    Allosteric inhibitors and di-ubiquitin NMR clarified USP7's catalytic mechanism, showing it preferentially binds and depolymerizes K48-linked chains and can be inhibited by attenuating ubiquitin binding rather than blocking the active site.

    Evidence NMR screening, co-crystal structures, isotope-labeled di-ubiquitin NMR, in vitro DUB assays

    PMID:29045385

    Open questions at the time
    • In-cell chain-linkage preference across substrates not mapped
    • Determinants of K48 vs K63 discrimination on physiologic substrates unknown
  15. 2018 Medium

    A rigorous negative study overturned the USP7-DNMT1 stabilization model, showing DNMT1 levels are unchanged in USP7-null cells and that USP7/PCNA recruitment to replication foci is DNMT1-independent.

    Evidence USP7-knockout mouse/human cells, DNMT1 GK→GQ knock-in, chromatin fractionation, immunofluorescence

    PMID:29482658

    Open questions at the time
    • Does not exclude context- or modification-specific DNMT1 effects
    • Original interaction's biological role left unexplained
  16. 2021 High

    Demonstrating preferential deubiquitination of polyQ-expanded androgen receptor, and protective effects of USP7 inhibition in SBMA/ALS models, redefined USP7 as a modifier of disease-protein proteostasis rather than a generic stabilizer.

    Evidence Quantitative proteomics, Co-IP, deubiquitination assays, conditional knockout mice, cross-species ALS models, behavioral assays

    PMID:33106424 PMID:33170804

    Open questions at the time
    • Basis of preference for expanded vs wild-type AR not structurally defined
    • Whether NEDD4L/SMAD2 axis fully accounts for ALS protection unclear
  17. 2024 Medium

    Mapping USP7 deubiquitination of KRAS at K147 via the TRAF domain extended its oncogenic substrate range to a major driver, reinforcing the therapeutic rationale across cancers.

    Evidence Co-IP, in vitro/in vivo deubiquitination, domain binding, ubiquitination-site mutagenesis, proliferation assays

    PMID:39499616

    Open questions at the time
    • Single-lab finding
    • Selectivity among KRAS isoforms/mutants not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP7 achieves substrate selectivity in cells — given an enormous reported substrate list, shared P/AXXS recognition, and tunable allosteric activation — and which substrates dominate its essential in vivo functions remains unresolved.
  • No quantitative ranking of physiologic substrates by occupancy/flux
  • p53-independent essential function (from knockout) lacks a defined effector
  • Most disease-context substrates rest on single-lab Co-IP without reconstitution

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 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-73894 DNA Repair 4 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
DAXXGMPSMCM-BPMDM2MDM4PPM1GTP53TRIP12

Evidence

Reading pass · 59 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 HAUSP/USP7 deubiquitinates and stabilizes both p53 and MDM2. Partial RNAi knockdown of HAUSP destabilizes p53, but nearly complete ablation stabilizes p53 indirectly by destabilizing MDM2 (which undergoes self-ubiquitination when HAUSP is absent). This reveals a dynamic feedback loop where HAUSP preferentially stabilizes MDM2 in normal cells. RNAi knockdown, co-immunoprecipitation, in vivo ubiquitination assays Molecular cell High 15053880
2006 The N-terminal TRAF-like domain of USP7 binds two closely spaced 4-residue sites in both p53 (residues 359–367) and MDM2 (residues 147–159), with a preference for a P/AXXS motif; Trp165 in the USP7 binding pocket is critical. Co-crystal structures of USP7 N-terminal domain with p53 and MDM2 peptides were determined, and the same surface also binds EBNA1, explaining competitive interactions. X-ray co-crystal structures, mutagenesis, peptide binding assays Nature structural & molecular biology High 16474402
2006 USP7/HAUSP interacts with and deubiquitinates FOXO4 in response to oxidative stress, negatively regulating FOXO4 transcriptional activity towards endogenous promoters. The monoubiquitination of FOXO4 drives its nuclear relocalization and increased transcriptional activity; USP7 reverses this without affecting FOXO4 protein half-life. Co-immunoprecipitation, in vivo and in vitro deubiquitination assays, nuclear localization imaging, transcriptional reporter assays Nature cell biology High 16964248
2005 HAUSP interacts with and directly deubiquitinates HDMX (MDM4), stabilizing it. HAUSP activity is required for normal HDMX protein levels, and the balance between HAUSP and HDM2 determines HDMX stability. ATM-dependent phosphorylation of HDMX and HDM2 reduces their affinity for HAUSP, contributing to their DNA-damage-induced destabilization. Co-immunoprecipitation, in vivo and in vitro deubiquitination assays, RNAi knockdown, DNA damage treatments Molecular cell High 15916963
2008 HAUSP/USP7 deubiquitinates PTEN, opposing its nuclear import. PML nuclear bodies coordinate PTEN localization through DAXX, which opposes HAUSP activity toward PTEN, so that PML-DAXX-HAUSP constitute a molecular network controlling PTEN deubiquitination and nuclear-cytoplasmic trafficking. Co-immunoprecipitation, in vivo deubiquitination assays, nuclear fractionation, RNAi knockdown, rescue experiments Nature High 18716620
2011 The 64 kDa C-terminal region of USP7 contains five ubiquitin-like (Ubl) domains organized in 2-1-2 units. The last di-Ubl unit (HUBL-45) activates USP7 ~100-fold by binding a 'switching' loop in the catalytic domain that promotes ubiquitin binding. The metabolic enzyme GMPS allosterically hyperactivates USP7 by binding the first three Ubl domains (HUBL-123) and stabilizing the HUBL-45-dependent active state. Crystal structure of USP7 C-terminal Ubl domains, in vitro deubiquitinase activity assays, domain deletion/mutagenesis Molecular cell High 21981925
2003 USP7 is a monomeric protein with four structural domains: an N-terminal p53-binding domain, a catalytic domain, and two C-terminal domains. The N-terminal domain binds both p53 and EBNA1 (EBNA1 with ~10-fold higher affinity), while ICP0 binds a distinct C-terminal domain (residues 599–801). Purified USP7 is active for cleaving both linear ubiquitin and ubiquitin conjugated to EBNA1. Partial proteolysis with MALDI-TOF-MS domain mapping, affinity pulldowns, tryptophan fluorescence binding assays, gel filtration, in vitro deubiquitinase assay The Journal of biological chemistry High 14506283
2007 A trimeric complex of p53, MDM2, and HAUSP can exist in vivo, despite the mutually exclusive binding of p53 and MDM2 to the USP7 TRAF domain, because MDM2 acts as a bridge. HAUSP can deubiquitinate p53 in trans via MDM2-mediated bridging even when direct p53-HAUSP interaction is disrupted by a p53 binding-deficient mutation. Co-immunoprecipitation in vivo and in vitro, structure-based mutagenesis, ubiquitination assays Oncogene Medium 17525743
2009 Hausp knockout mice die between embryonic days E6.5 and E7.5 with p53 activation. Lethality is caused by reduced proliferation and developmental arrest partly attributable to p53 activation. Deletion of p53 extends but does not completely rescue embryonic development of hausp knockouts, indicating both p53-dependent and p53-independent essential functions of HAUSP in vivo. Conditional and conventional knockout mice, genetic epistasis (hausp/p53 double knockout), embryo analysis Oncogene High 19946331
2012 USP7 stability is regulated by CK2-mediated phosphorylation at serine 18, which stabilizes the USP7S isoform and thus maintains MDM2 stability and p53 repression in unstressed cells. After ionizing radiation, ATM-dependent phosphatase PPM1G dephosphorylates USP7S, leading to its downregulation, MDM2 destabilization, and p53 accumulation. Phosphorylation mapping, kinase/phosphatase assays, RNAi, IR treatment, Western blotting Molecular cell High 22361354
2011 Kaposi's sarcoma-associated herpesvirus vIRF4 inhibits HAUSP through a bilateral belt-type interaction: vif1 peptide binds the HAUSP TRAF domain blocking substrate binding, while vif2 peptide binds both the TRAF and catalytic domains to suppress deubiquitinase activity. Crystal structures of the HAUSP-vIRF4 complexes were determined. X-ray crystal structure, peptide competition assays, deubiquitinase activity assays, cell-based apoptosis/xenograft assays Nature structural & molecular biology High 22056774
2016 HAUSP/USP7 deubiquitinates and stabilizes N-Myc (MYCN) in neuroblastoma. HAUSP interacts with N-Myc; HAUSP overexpression induces N-Myc deubiquitination and stabilization, while USP7 RNAi or genetic ablation (Usp7 knockout in mouse brain) destabilizes N-Myc and inhibits its function. Co-immunoprecipitation, in vivo deubiquitination assays, RNAi knockdown, conditional knockout mice, xenograft models, USP7 inhibitors Nature medicine High 27618649
2017 Small-molecule inhibitors GNE-6640 and GNE-6776 non-covalently target USP7 12 Å from the catalytic cysteine, attenuating ubiquitin binding rather than directly blocking the active site. Structural studies showed these compounds interact with acidic residues mediating hydrogen bonds with ubiquitin Lys48, and NMR with isotopically labeled di-ubiquitin chains showed USP7 preferentially binds free Lys48 side chains, protracted depolymerization of K48-linked chains relative to K63-linked chains. NMR-based screening, co-crystal structures, differential isotope-labeled di-ubiquitin NMR binding assays, in vitro deubiquitinase activity assays Nature High 29045385
2015 Genotoxic stress stimulates Cry1 phosphorylation and its deubiquitination by HAUSP/USP7, stabilizing Cry1 and shifting circadian clock phase. USP7 deubiquitinates Cry1 to protect it from degradation following DNA damage. Co-immunoprecipitation, in vivo deubiquitination assays, clock phase measurements, DNA damage treatments eLife Medium 25756610
2015 USP7 deubiquitinates Ci/Gli transcription factors in the Hedgehog pathway, inhibiting their Slimb-Cul1 and Hib-Cul3 E3-ligase-mediated ubiquitination and degradation. Hh stimulation promotes Usp7 binding to Ci. Usp7 forms a complex with GMPS to promote Hh pathway activity, and the mammalian homolog HAUSP similarly regulates Gli ubiquitination and stability. Co-immunoprecipitation, in vivo ubiquitination assays, Drosophila genetics, mammalian cell assays Developmental cell High 26120032
2015 USP7 controls Chk1 protein stability by direct deubiquitination. Depletion or inhibition of USP7 lowers Chk1 levels; overexpression of catalytically active (but not catalytic mutant) USP7 elevates Chk1 levels and increases its half-life. Catalytic mutant USP7 fails to deubiquitinate Chk1 in vivo and in vitro. This effect is independent of USP7's known stabilization of Claspin. RNAi, overexpression of wild-type vs. catalytic mutant USP7, in vivo and in vitro deubiquitination assays, half-life measurements Cell cycle Medium 25483066
2015 USP7 maintains Rad18 protein stability by direct deubiquitination. USP7 associates with Rad18 via a consensus USP7-binding motif (PVDS or similar). Loss of USP7 destabilizes Rad18, compromises UV-induced PCNA mono-ubiquitination and Pol η recruitment, and impairs DNA damage tolerance. USP7 can disassemble Rad18-dependent poly-ubiquitin chains in vitro and in vivo. Co-immunoprecipitation, in vitro and in vivo deubiquitination assays, RNAi, UV irradiation, PCNA ubiquitination assays, replication fork analysis Oncogene High 25961918
2013 USP7 directly interacts with MCM-BP via the PSTS(155-158) motif engaging the TRAF domain binding pocket of USP7. USP7 knockout leads to slowed S phase progression and accumulation of MCM proteins on chromatin due to a defect in MCM complex unloading during mid-to-late S phase. USP7 works with MCM-BP to facilitate MCM unloading from chromatin at the end of S phase. Co-immunoprecipitation, structural analysis of USP7-MCM-BP interaction, USP7 knockout cell analysis, chromatin fractionation, DNA replication assays Molecular and cellular biology High 24190967
2016 HAUSP deubiquitinates HIF-1α to increase its stability and promotes EMT/metastasis. Hypoxia induces K63-linked polyubiquitination of HAUSP at K443, enhancing its functions. K63-polyubiquitinated HAUSP interacts with ubiquitin receptor CBP to specifically mediate H3K56 acetylation at HIF-1α target gene promoters. HectH9 is the E3 ligase responsible for K63-ubiquitination of HAUSP. Co-immunoprecipitation, in vivo deubiquitination assays, ChIP-seq, mutagenesis, RNAi knockdown, metastasis assays Nature communications Medium 27934968
2016 Trip12 functions as an E3 ubiquitin ligase for USP7/HAUSP, controlling USP7 protein stability through the ubiquitin-proteasome pathway. Trip12 knockdown increases USP7-mediated stabilization of p53, 53BP1, and Chk1; Trip12 overexpression phenocopies USP7 knockdown (increased S-phase cells). Co-immunoprecipitation, in vivo ubiquitination assays, RNAi, cell cycle analysis FEBS letters Medium 27800609
2010 USP7 modulates chromatin remodeling important for base excision repair of oxidative lesions. USP7 siRNA knockdown does not change the levels or activity of BER enzymes but significantly reduces chromatin DNA accessibility and consequently the rate of repair of oxidative lesions. siRNA knockdown, chromatin accessibility assays, BER activity assays Nucleic acids research Medium 21138959
2014 HAUSP/USP7 deubiquitinates retinoblastoma protein (Rb), removing K48-linked ubiquitin chains from Rb and stabilizing it from proteasomal degradation. HAUSP deubiquitination of Rb leads to increased G1 cell population. In glioma, MDM2 becomes the preferred USP7 substrate over Rb, facilitating Rb degradation. Co-immunoprecipitation, in vivo and in vitro deubiquitination assays, cell cycle analysis, immunohistochemistry The FEBS journal Medium 24823443
2007 USP7 interacts with and deubiquitinates the mitotic checkpoint protein Chfr, stabilizing it. USP7 removes ubiquitin from autoubiquitinated Chfr both in vivo and in vitro. The USP7-Chfr interaction was identified by immunoaffinity purification and mass spectrometry. Immunoaffinity purification and mass spectrometry, co-immunoprecipitation, in vivo and in vitro deubiquitination assays Biochemical and biophysical research communications Medium 17442268
2019 Usp7 deubiquitinates and stabilizes Yorkie (Yki) in Drosophila, positively regulating Hippo pathway output. Hippo pathway activation attenuates Usp7-Yki binding. The mammalian homolog HAUSP similarly stabilizes YAP by modulating its ubiquitination and degradation. Co-immunoprecipitation, in vivo ubiquitination assays, Drosophila genetics, mammalian cell assays Nature communications Medium 30679505
2018 USP7 and USP47 regulate NLRP3 inflammasome activation in macrophages. Chemical inhibition of USP7 and USP47 blocks inflammasome formation by preventing ASC oligomerization and speck formation, independently of transcription. Inhibition alters the ubiquitination status of NLRP3 itself. USP7 and USP47 activity increases in response to inflammasome activators. CRISPR/Cas9 knockdown, chemical inhibition, ASC speck formation assays, ubiquitination assays, IL-1β/IL-18 cytokine measurement EMBO reports Medium 30206189
2021 USP7 interacts with and supports PP2A active localization in the cytoplasm. Inhibition of USP7 or PP2A produces similar phosphoproteomic changes including widespread increase in CDK1 substrate phosphorylation. USP7 inhibition causes untimely CDK1 activation throughout the cell cycle, leading to DNA damage; this toxicity is rescued by lowering CDK1 activity or chemically activating PP2A. Co-immunoprecipitation, quantitative phosphoproteomics, kinase activity assays, genetic and chemical rescue experiments The EMBO journal Medium 33856059
2018 USP7 deubiquitinates and stabilizes NOTCH1 in T-ALL cells. USP7 interacts with NOTCH1 via its MATH and UBL domains. USP7 knockdown increases NOTCH1 ubiquitination and reduces NOTCH1 protein levels, suppressing T-ALL proliferation in vitro and in vivo. Co-immunoprecipitation, in vivo and in vitro deubiquitination assays, RNAi, domain mapping, xenograft models Signal transduction and targeted therapy Medium 30370059
2017 USP7 stabilizes HIV-1 Tat protein through deubiquitination. USP7 knockdown by CRISPR-Cas9 reduces Tat protein levels and reduces virus production. Endogenous USP7 levels increase after HIV-1 infection in human T-cells. CRISPR-Cas9 knockout, USP7 inhibitor treatment, co-immunoprecipitation, virus production assays The Biochemical journal Medium 28280111
2010 USP7 promotes p53 sequence-specific DNA binding activity through interaction with the C-terminal regulatory region of p53, independent of USP7's N-terminal domain and independent of deubiquitylation activity. The USP7 C-terminal domain alone is sufficient to promote p53 binding to target sequences and p21 induction. In vitro DNA binding assays, domain mutagenesis, overexpression of catalytically inactive USP7, p21 expression assays PloS one Medium 20885946
2020 USP7 deubiquitinates and stabilizes PD-L1 by direct interaction. Abrogation of USP7 attenuates PD-L1/PD-1 interaction and sensitizes cancer cells to T cell killing in vitro and in vivo. Co-immunoprecipitation, in vivo ubiquitination assays, T cell killing assays, xenograft models Acta pharmaceutica Sinica. B Medium 33777676
2021 USP7 preferentially interacts with polyQ-expanded androgen receptor (AR) and deubiquitinates it, reducing AR ubiquitination and promoting mutant AR aggregation. USP7 knockdown or monoallelic Usp7 knockout in mice reduces mutant AR aggregation and ameliorates SBMA motor phenotypes. USP7 also differentially interacts with mutant Huntingtin in striatum and frontal cortex. Quantitative proteomics, co-immunoprecipitation, in vivo ubiquitination assays, RNAi, conditional knockout mice, behavioral assays The Journal of clinical investigation High 33170804
2020 USP7 deubiquitinates NEDD4L (an E3 ubiquitin ligase for SMAD2), stabilizing NEDD4L and thereby reducing SMAD2 levels, which decreases autophagy-mediated clearance of misfolded proteins. In ALS models across C. elegans, Drosophila, and mammalian cells, USP7 inhibition protects against proteotoxicity through the SMAD2/TGF-β pathway. Genetic screen in C. elegans, Drosophila and mammalian cell validation, co-immunoprecipitation, deubiquitination assays, autophagy assays Proceedings of the National Academy of Sciences of the United States of America High 33106424
2019 USP7 stabilizes FBXO38 dependent on its catalytic activity. FBXO38 in turn stabilizes KIF20B (a kinesin required for cytokinesis) independent of an SCF complex. Depletion of USP7 or FBXO38 reduces KIF20B levels and causes cytokinetic defects that can be rescued by restoring FBXO38 or KIF20B. Affinity purification-mass spectrometry, BioID protein interaction profiling, Co-immunoprecipitation, RNAi, rescue experiments, cytokinesis imaging Scientific reports Medium 30804394
2018 USP7 interacts with and stabilizes DDX24 and DHX40 (DEAD/DEAH-box RNA helicases) dependent on its catalytic activity. USP7 interacts with PPM1G, TRIP12, and USP11 through its TRAF domain binding pocket (via P/A/ExxS motifs), whereas DHX40 uses a distinct binding site in the Ubl2 domain. Affinity purification-mass spectrometry, USP7 TRAF-domain binding-pocket mutants, RNAi and inhibitor treatments, Western blotting Scientific reports Medium 30367141
2022 USP7 deubiquitinates and stabilizes EZH2 in prostate cancer cells. USP7 knockdown decreases EZH2 protein and inhibits EZH2-dependent transcriptional repression. The USP7/EZH2 axis promotes cancer cell migration, invasion, and sphere formation. Co-immunoprecipitation, in vivo ubiquitination assays, RNAi, ectopic EZH2 rescue, cell migration/invasion assays Genetics and molecular biology Medium 32453339
2022 USP7 deubiquitinates and stabilizes HO-1 (heme oxygenase-1) to regulate redox homeostasis. Under arsenic exposure, USP7 itself becomes ubiquitinated at K476, which promotes its binding to HO-1, leading to enhanced HO-1 deubiquitination and stabilization. HO-1 is ubiquitinated at K243 under resting conditions. Co-immunoprecipitation, in vivo deubiquitination assays, ubiquitination site mapping, arsenic stress experiments, knockdown Oncogene Medium 35821281
2022 USP7 deubiquitinates and stabilizes Raf-1. USP7 binds the PVDS motif in the CR2 region of Raf-1 and removes K6-, K11-, K27-, K33-, and K48-linked polyubiquitin chains. USP7-mediated deubiquitination of Raf-1 decreases Raf-1 threonine phosphorylation and inhibits ERK1/2 signaling, thereby restraining the G2/M transition in lung adenocarcinoma cells. Bioinformatics motif analysis, Co-immunoprecipitation, in vivo ubiquitination assays, phosphorylation assays, ERK signaling assays, cell cycle analysis Cell death & disease Medium 35948545
2022 USP7 deubiquitinates and stabilizes TAZ by selectively removing K48-linked ubiquitination, antagonizing β-TRCP-mediated ubiquitin-proteasomal degradation and enhancing TAZ nuclear retention and transcriptional output in HNSCC. siRNA/cDNA library screens, Co-immunoprecipitation, in vivo ubiquitination assays, nuclear localization assays, xenograft and PDX models Cell death & disease Medium 35931679
2022 Natural compound eupalinolide B (EB) covalently and allosterically inhibits USP7 at Cys576 in the non-catalytic HUBL domain (not the active site). Co-crystal structure reveals this previously undisclosed binding site. Modification of Cys576 allosterically inhibits USP7, causing ubiquitination-dependent degradation of Keap1, leading to Nrf2-dependent transcription of anti-neuroinflammatory genes in microglia. Co-crystal structure, covalent binding assays, ubiquitination assays, Nrf2 target gene expression, in vivo mouse models of neurodegeneration Science advances High 35947662
2024 USP7 directly deubiquitinates KRAS by binding KRAS via its TRAF domain and removing K48-linked polyubiquitin chains from KRAS K147, stabilizing KRAS and promoting NSCLC proliferation. USP7 also stabilizes oncogenic KRAS mutants through deubiquitination. Co-immunoprecipitation, in vivo and in vitro deubiquitination assays, domain binding assays, ubiquitination site mutagenesis, NSCLC cell proliferation assays Cell reports Medium 39499616
2021 USP7 deubiquitinates and stabilizes BCR-ABL fusion protein in CML cells. USP7 interacts with BCR-ABL and blocks its polyubiquitination; knockdown or chemical inhibition of USP7 triggers BCR-ABL degradation and suppresses downstream signaling. DUB screen, co-immunoprecipitation, in vivo ubiquitination assays, RNAi, USP7 inhibitors, apoptosis assays Cell death & disease Medium 33963175
2019 USP7 deubiquitinates and stabilizes Maf proteins (c-Maf, MafA, MafB) in myeloma cells, promoting their transcriptional activity as measured by luciferase assays and Maf-regulated gene expression. Mass spectrometry identification, co-immunoprecipitation, in vivo ubiquitination assays, RNAi, luciferase reporter assays The Journal of biological chemistry Medium 31822558
2019 USP7 deubiquitinates and stabilizes SIRT1, cleaving K48-linked polyubiquitin chains. USP7 is physically associated with SIRT1 as identified by mass spectrometry. USP7 enzymatic inhibition leads to decreased SIRT1 expression and accumulation of SIRT1 polyubiquitination. Mass spectrometry, co-immunoprecipitation, in vivo ubiquitination assays, USP7 inhibitor treatment Anatomical record Low 31502386
2016 Trip12 acts as an E3 ubiquitin ligase for USP7, regulating USP7 protein stability through the ubiquitin-proteasome pathway, and consequently affecting USP7-mediated stabilization of p53, 53BP1, and Chk1 in the DNA damage response. Co-immunoprecipitation, in vivo ubiquitination assays, RNAi, cell cycle analysis FEBS letters Medium 27800609
2022 USP7 is identified as a deubiquitinase for XIAP in a p53-independent pathway. USP7 deubiquitinates XIAP to inhibit caspase-dependent apoptosis. Combined inhibition of USP7 and XIAP induces apoptosis in vitro and in vivo in glioma, correlating with grade-wise co-accumulation of USP7 and XIAP in tumor tissue. Proteomics analysis, co-immunoprecipitation, in vivo deubiquitination assays, RNAi, caspase activity assays, in vivo xenograft, IHC Oncogene Medium 36243803
2020 USP7 deubiquitinates and stabilizes ZNF638, and also facilitates ZNF638 transcription via CREB stabilization. The USP7/ZNF638 axis increases SREBP1C cleavage through AKT/mTORC1/S6K signaling and forms a nuclear complex with SREBP1C to regulate lipogenesis-associated enzymes (ACACA, FASN, SCD) in hepatocytes. Co-immunoprecipitation, in vivo deubiquitination assays, ChIP assays, RNAi, liver steatosis mouse model Cell death & disease Medium 33040080
2022 USP7 deubiquitinates and stabilizes ABCB1 (P-glycoprotein/MDR1) through direct interaction, promoting chemoresistance in triple-negative breast cancer. USP7 overexpression increases ABCB1-mediated drug efflux resistance, while USP7 knockdown sensitizes resistant cells. Co-immunoprecipitation, in vivo ubiquitination assays, RNAi, drug resistance assays Cells Low 36291159
2022 USP7 deubiquitinates and stabilizes RECQL4, counteracting UBE2O-mediated multi-monoubiquitination and proteasomal degradation of RECQL4. USP7 interacts with both UBE2O and RECQL4, and antagonizes UBE2O-mediated inhibition of homologous recombination DNA repair. Co-immunoprecipitation, in vivo ubiquitination assays, HR assays, RNAi FASEB journal Medium 34921745
2023 USP7 deubiquitinates and stabilizes KDM5B (lysine-specific demethylase 5B) in nasopharyngeal carcinoma. KDM5B inhibits ZBTB16 expression by reducing H3K4me3 at its promoter, subsequently increasing TOP2A expression and conferring cisplatin resistance. Co-immunoprecipitation, in vivo deubiquitination assays, H3K4me3 ChIP, RNAi, xenograft models Cell death and differentiation Medium 38287116
2023 USP7 deubiquitinates TRIM24, stabilizing it. TRIM24 then promotes SPLUNC1 expression via STAT3 recruitment in M1 macrophages, driving M1 polarization and suppressing NPC tumor progression. Co-immunoprecipitation, in vivo ubiquitination assays, ChIP, RNAi, xenograft models Cell death & disease Low 38129408
2023 USP7 directly binds and deubiquitinates HMOX-1 (HO-1) in spinal cord injury context. USP7 overexpression promotes HMOX-1 expression via deubiquitination, reducing ferroptosis and ameliorating spinal cord injury in rat models. Co-immunoprecipitation, in vivo ubiquitination assays, SCI rat model, behavioral/histological assays Neurochemistry international Low 37257587
2023 USP7 promotes osteoclast differentiation via deubiquitination and stabilization of HMGB1, which promotes osteoclast formation. USP7 inhibition attenuates bone loss in OVX mice. Co-immunoprecipitation, in vivo ubiquitination assays, osteoclast differentiation assays, in vivo OVX mouse model Journal of orthopaedic translation Low 37333461
2023 USP7 inhibits osteoclastogenesis via two mechanisms: (1) impairing K63-linked polyubiquitination of TRAF6 (without affecting TRAF6 stability), thereby suppressing RANKL-mediated NF-κB and MAPK activation; (2) protecting STING from degradation to induce IFN-β expression. USP7 overexpression impairs osteoclast differentiation and bone resorption in vivo. Co-immunoprecipitation, in vivo ubiquitination assays, osteoclast differentiation assays, NF-κB/MAPK pathway assays, OVX mouse model Aging and disease Medium 37199589
2022 RRM2 (ribonucleotide reductase regulatory subunit) is a USP7 substrate regulated during S phase. USP7 depletion induces cellular senescence in melanoma, and ectopic RRM2 expression in USP7-depleted cells rescues the senescent phenotype, placing RRM2 as a key USP7 substrate in cell cycle regulation. In vivo drop-out screens in PDX models, global transcriptomics and proteomics, RNAi, ectopic expression rescue, senescence assays Cell reports Medium 36130505
2022 USP7 deubiquitinates and stabilizes ERβ in NSCLC. ERβ suppresses PRDX3 SUMOylation, reducing ROS accumulation and promoting osimertinib resistance. USP7 depletion reduces ERβ and reverses osimertinib resistance. Co-immunoprecipitation, in vivo deubiquitination assays, SUMOylation assays, ROS measurement, drug resistance assays, in vivo xenograft Cancer letters Low 38097136
2024 USP7 deubiquitinates and stabilizes LARS1 (leucyl-tRNA synthetase 1). The mitochondrial peptide MOTS-c competes with USP7 for binding to LARS1, attenuating USP7-mediated LARS1 deubiquitination and promoting LARS1 ubiquitination and degradation. Co-immunoprecipitation, in vivo ubiquitination assays, competition binding assays, ovarian cancer cell and mouse model experiments Advanced science Low 39321430
2005 HAUSP is itself polyubiquitinated, polyneddylated, and can dimerize. A catalytic mutant (C224S) of HAUSP contributes to p53 destabilization in a dose-dependent manner, consistent with dominant-negative interference. Co-immunoprecipitation, reporter cell line (p53 response element-lacZ), overexpression of wild-type and C224S mutant HAUSP FEBS letters Low 16111684
2024 USP7 deubiquitinates and stabilizes KPNB1 (importin β1) in glioblastoma. USP7-stabilized KPNB1 mediates nuclear import of transcription factor YBX1, which transcriptionally activates NLGN3, promoting GBM progression. Co-immunoprecipitation, ubiquitination assays, nuclear fractionation, ChIP assays, RNAi, intracranial xenograft models Journal of experimental & clinical cancer research Low 38254206
2018 USP7 and the DNMT1 interaction via GK-repeat acetylation was reported to stabilize DNMT1; however, direct experimental testing showed that DNMT1 is present at normal levels in cells lacking USP7, and substitution of GK repeats to prevent acetylation does not affect DNMT1 stability. USP7 and PCNA are recruited to replication foci independently of DNMT1. This negative result indicates the USP7-DNMT1 stabilization model is not supported. Knockout cell lines (mouse and human lacking USP7), DNMT1 GK→GQ mutant knockin, chromatin fractionation, immunofluorescence Epigenetics & chromatin Medium 29482658

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 A dynamic role of HAUSP in the p53-Mdm2 pathway. Molecular cell 566 15053880
2008 The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature 455 18716620
2006 FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nature cell biology 406 16964248
2017 USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature 278 29045385
2009 Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Molecular cancer therapeutics 276 19671755
2006 Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nature structural & molecular biology 266 16474402
2020 USP7 targeting modulates anti-tumor immune response by reprogramming Tumor-associated Macrophages in Lung Cancer. Theranostics 236 32802195
2005 Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2. Molecular cell 227 15916963
2012 Discovery of specific inhibitors of human USP7/HAUSP deubiquitinating enzyme. Chemistry & biology 225 22520753
2011 Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase. Molecular cell 222 21981925
2016 HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma. Nature medicine 172 27618649
2019 USP7: Structure, substrate specificity, and inhibition. DNA repair 160 30807924
2018 USP7 and USP47 deubiquitinases regulate NLRP3 inflammasome activation. EMBO reports 159 30206189
2009 Inactivation of HAUSP in vivo modulates p53 function. Oncogene 155 19946331
2003 Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP. The Journal of biological chemistry 149 14506283
2018 Emerging insights into HAUSP (USP7) in physiology, cancer and other diseases. Signal transduction and targeted therapy 138 29967688
2012 ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage. Molecular cell 130 22361354
2007 The p53--Mdm2--HAUSP complex is involved in p53 stabilization by HAUSP. Oncogene 121 17525743
2020 Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing. Acta pharmaceutica Sinica. B 118 33777676
2005 ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell cycle (Georgetown, Tex.) 118 16082221
2020 Targeting USP7-Mediated Deubiquitination of MDM2/MDMX-p53 Pathway for Cancer Therapy: Are We There Yet? Frontiers in cell and developmental biology 116 32300595
2016 K63-polyubiquitinated HAUSP deubiquitinates HIF-1α and dictates H3K56 acetylation promoting hypoxia-induced tumour progression. Nature communications 109 27934968
2022 Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy. Science advances 99 35947662
2015 DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization. eLife 97 25756610
2020 USP7 Is a Master Regulator of Genome Stability. Frontiers in cell and developmental biology 87 32850836
2018 USP7: Target Validation and Drug Discovery for Cancer Therapy. Medicinal chemistry (Shariqah (United Arab Emirates)) 87 29065837
2017 Regulation of USP7: A High Incidence of E3 Complexes. Journal of molecular biology 85 28591556
2023 USP7 - a crucial regulator of cancer hallmarks. Biochimica et biophysica acta. Reviews on cancer 83 37127084
2006 The HAUSP gene plays an important role in non-small cell lung carcinogenesis through p53-dependent pathways. The Journal of pathology 82 16450335
2019 Usp7 regulates Hippo pathway through deubiquitinating the transcriptional coactivator Yorkie. Nature communications 81 30679505
2017 Modulation of the p53/MDM2 interplay by HAUSP inhibitors. Journal of molecular cell biology 80 27927749
2015 Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling. Developmental cell 80 26120032
2014 USP7 controls Chk1 protein stability by direct deubiquitination. Cell cycle (Georgetown, Tex.) 74 25483066
2011 Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein. Nature structural & molecular biology 74 22056774
2020 The emerging nature of Ubiquitin-specific protease 7 (USP7): a new target in cancer therapy. Drug discovery today 64 33157193
2015 USP7 is essential for maintaining Rad18 stability and DNA damage tolerance. Oncogene 64 25961918
2011 Roles of HAUSP-mediated p53 regulation in central nervous system development. Cell death and differentiation 64 21350561
2013 A role for USP7 in DNA replication. Molecular and cellular biology 63 24190967
2022 Discovery of a Potent and Selective Degrader for USP7. Angewandte Chemie (International ed. in English) 54 35691827
2018 USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia. Signal transduction and targeted therapy 54 30370059
2020 The USP7 protein interaction network and its roles in tumorigenesis. Genes & diseases 49 35005106
2022 Highlights in USP7 inhibitors for cancer treatment. Frontiers in chemistry 48 36186590
2014 HAUSP, a novel deubiquitinase for Rb - MDM2 the critical regulator. The FEBS journal 48 24823443
2013 Expression of HAUSP in gliomas correlates with disease progression and survival of patients. Oncology reports 48 23483195
2018 Identification and Characterization of USP7 Targets in Cancer Cells. Scientific reports 46 30367141
2004 HAUSP/USP7 as an Epstein-Barr virus target. Biochemical Society transactions 46 15494000
2017 USP7 deubiquitinase controls HIV-1 production by stabilizing Tat protein. The Biochemical journal 44 28280111
2007 Deubiquitination of Chfr, a checkpoint protein, by USP7/HAUSP regulates its stability and activity. Biochemical and biophysical research communications 44 17442268
2020 USP7 mediates pathological hepatic de novo lipogenesis through promoting stabilization and transcription of ZNF638. Cell death & disease 43 33040080
2020 USP7 regulates ALS-associated proteotoxicity and quality control through the NEDD4L-SMAD pathway. Proceedings of the National Academy of Sciences of the United States of America 43 33106424
2019 The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival. The Journal of biological chemistry 43 31822558
2016 Trip12 is an E3 ubiquitin ligase for USP7/HAUSP involved in the DNA damage response. FEBS letters 43 27800609
2024 Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis. Cell death and differentiation 42 38287116
2024 USP7 as an emerging therapeutic target: A key regulator of protein homeostasis. International journal of biological macromolecules 42 38382779
2021 Recent advances on the intervention sites targeting USP7-MDM2-p53 in cancer therapy. Bioorganic chemistry 42 34474304
2020 USP7 deubiquitinates and stabilizes EZH2 in prostate cancer cells. Genetics and molecular biology 41 32453339
2013 UVSSA and USP7, a new couple in transcription-coupled DNA repair. Chromosoma 38 23760561
2007 Proteome changes induced by knock-down of the deubiquitylating enzyme HAUSP/USP7. Journal of proteome research 38 17927229
2024 Exosomal circ-0100519 promotes breast cancer progression via inducing M2 macrophage polarisation by USP7/NRF2 axis. Clinical and translational medicine 36 39107958
2022 USP7 regulates the ERK1/2 signaling pathway through deubiquitinating Raf-1 in lung adenocarcinoma. Cell death & disease 36 35948545
2006 HAUSP as a therapeutic target for hematopoietic tumors (review). International journal of oncology 35 16596237
2023 USP7 regulates HMOX-1 via deubiquitination to suppress ferroptosis and ameliorate spinal cord injury in rats. Neurochemistry international 34 37257587
2015 Annexin-1 regulated by HAUSP is essential for UV-induced damage response. Cell death & disease 34 25695607
2010 USP7/HAUSP stimulates repair of oxidative DNA lesions. Nucleic acids research 34 21138959
2023 USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24. Cell death & disease 33 38129408
2022 USP7-SOX9-miR-96-5p-NLRP3 Network Regulates Myocardial Injury and Cardiomyocyte Pyroptosis in Sepsis. Human gene therapy 33 35686454
2022 Targeting the USP7/RRM2 axis drives senescence and sensitizes melanoma cells to HDAC/LSD1 inhibitors. Cell reports 32 36130505
2022 USP7 Inhibitors in Cancer Immunotherapy: Current Status and Perspective. Cancers 32 36428632
2021 USP7 limits CDK1 activity throughout the cell cycle. The EMBO journal 31 33856059
2015 HAUSP-nucleolin interaction is regulated by p53-Mdm2 complex in response to DNA damage response. Scientific reports 31 26238070
2022 The deubiquitinase USP7 promotes HNSCC progression via deubiquitinating and stabilizing TAZ. Cell death & disease 30 35931679
2024 USP7 deubiquitinates KRAS and promotes non-small cell lung cancer. Cell reports 29 39499616
2022 TRIM27-USP7 complex promotes tumour progression via STAT3 activation in human hepatocellular carcinoma. Liver international : official journal of the International Association for the Study of the Liver 29 35753056
2019 USP7 Regulates Cytokinesis through FBXO38 and KIF20B. Scientific reports 29 30804394
2023 USP7-mediated ERβ stabilization mitigates ROS accumulation and promotes osimertinib resistance by suppressing PRDX3 SUMOylation in non-small cell lung carcinoma. Cancer letters 28 38097136
2022 USP7 targets XIAP for cancer progression: Establishment of a p53-independent therapeutic avenue for glioma. Oncogene 28 36243803
2021 Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis. Cell death & disease 28 33963175
2024 USP7-Based Deubiquitinase-Targeting Chimeras Stabilize AMPK. Journal of the American Chemical Society 27 38597345
2022 The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1. Oncogene 27 35821281
2022 USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1. Cells 27 36291159
2022 USP7 substrates identified by proteomics analysis reveal the specificity of USP7. Genes & development 27 36302555
2017 Usp7 promotes medulloblastoma cell survival and metastasis by activating Shh pathway. Biochemical and biophysical research communications 27 28137592
2015 HAUSP regulates c-MYC expression via de-ubiquitination of TRRAP. Cellular oncology (Dordrecht, Netherlands) 27 25925205
2021 Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy. The Journal of clinical investigation 26 33170804
2020 USP7 manipulation by viral proteins. Virus research 25 32603670
2023 Ubiquitin-specific protease 7 (USP7): an emerging drug target for cancer treatment. Expert opinion on therapeutic targets 24 37789645
2010 USP7/HAUSP promotes the sequence-specific DNA binding activity of p53. PloS one 24 20885946
2023 USP7 Inhibits Osteoclastogenesis via Dual Effects of Attenuating TRAF6/TAK1 Axis and Stimulating STING Signaling. Aging and disease 23 37199589
2023 USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination. Journal of orthopaedic translation 23 37333461
2020 Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance. International journal of molecular sciences 23 33207738
2020 USP7 stabilizes EZH2 and enhances cancer malignant progression. American journal of cancer research 22 32064169
2024 Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation. Acta pharmacologica Sinica 21 38589688
2024 The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis. Cell death & disease 21 38769122
2022 UBE2O and USP7 co-regulate RECQL4 ubiquitinylation and homologous recombination-mediated DNA repair. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 34921745
2018 Independent functions of DNMT1 and USP7 at replication foci. Epigenetics & chromatin 20 29482658
2005 HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized. FEBS letters 20 16111684
2023 USP7- and PRMT5-dependent G3BP2 stabilization drives de novo lipogenesis and tumorigenesis of HNSC. Cell death & disease 19 36878903
2019 USP7 Deubiquitinates and Stabilizes SIRT1. Anatomical record (Hoboken, N.J. : 2007) 19 31502386
2024 Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis. Journal of experimental & clinical cancer research : CR 18 38254206
2024 Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39321430

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