Affinage

USP7

Ubiquitin carboxyl-terminal hydrolase 7 · UniProt Q93009

Length
1102 aa
Mass
128.3 kDa
Annotated
2026-04-28
100 papers in source corpus 56 papers cited in narrative 56 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP7 is a cysteine deubiquitinase that functions as a master regulator of protein stability across the p53-MDM2 axis, DNA damage response, chromatin regulation, and multiple developmental and oncogenic signaling pathways. Its catalytic domain is intrinsically autoinhibited and requires activation by its C-terminal ubiquitin-like domains (HUBL-45), with further allosteric hyperactivation by GMPS; substrates are recruited primarily through a P/A/ExxS motif that binds the N-terminal TRAF-like domain, which is also exploited by viral proteins such as EBNA1 and KSHV vIRF4 (PMID:16474402, PMID:21981925, PMID:22056774). USP7 deubiquitinates and stabilizes p53 directly, yet preferentially stabilizes MDM2 and MDMX under basal conditions, establishing a dynamic feedback loop in which CK2 phosphorylation maintains USP7 stability and DNA damage triggers ATM/PPM1G-mediated dephosphorylation to shift the balance toward p53 activation (PMID:11923872, PMID:15053880, PMID:15916963, PMID:22361354). Beyond p53 signaling, USP7 deubiquitinates substrates spanning chromatin regulation (EZH2, H2BK120ub1, RNF168, KDM5B), DNA repair and replication (Chk1, Rad18, MCM-BP, RRM2), and key signaling effectors (PTEN, FOXO4, HIF-1α, β-catenin, KRAS, YAP/TAZ, Gli, NOTCH1, Raf-1), thereby influencing cell cycle progression, the Hedgehog and Hippo pathways, Wnt signaling, and immune checkpoint regulation (PMID:18716620, PMID:25894431, PMID:25961918, PMID:33849069, PMID:30679505, PMID:39499616, PMID:26120032, PMID:27934968). USP7 knockout is embryonic lethal in mice, partially rescued by p53 deletion, confirming both p53-dependent and p53-independent essential functions in vivo (PMID:19946331, PMID:21350561).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    The identity of the deubiquitinase that counteracts MDM2-mediated p53 degradation was unknown; demonstration that USP7/HAUSP directly deubiquitinates p53 in vitro and in vivo established the first substrate and the paradigm that a DUB can stabilize a tumor suppressor against proteasomal degradation.

    Evidence Affinity purification/MS identification of p53-USP7 interaction; in vitro deubiquitination assay with catalytic-dead mutant in human cells

    PMID:11923872

    Open questions at the time
    • Whether USP7 is the sole DUB for p53 was not addressed
    • Structural basis of p53 recognition unknown
    • Physiological in vivo relevance not yet tested in animal models
  2. 2003 High

    How viral proteins hijack USP7 was unclear; mapping revealed that EBNA1 binds the same N-terminal TRAF domain as p53 with higher affinity while HSV-1 ICP0 binds a distinct C-terminal region, establishing that the TRAF domain is the primary substrate-recognition module and that viruses exploit it competitively.

    Evidence MALDI-TOF domain mapping; tryptophan fluorescence binding assays; competition experiments with EBNA1 and p53 peptides

    PMID:14506283

    Open questions at the time
    • How ICP0 binding to the C-terminal domain affects USP7 catalysis was undefined
    • Whether EBNA1 displacement of p53 is the primary viral immune evasion mechanism was unclear
  3. 2004 High

    The paradox that complete USP7 ablation activates rather than destabilizes p53 was resolved by showing that USP7 preferentially stabilizes MDM2 under basal conditions, revealing a feedback loop where the net effect of USP7 activity depends on its expression level.

    Evidence RNAi knockdown of endogenous HAUSP with analysis of MDM2 and p53 protein levels across cell lines

    PMID:15053880

    Open questions at the time
    • Quantitative parameters governing the switch between p53 and MDM2 stabilization not defined
    • Whether additional substrates contribute to the p53 pathway effect was unknown
  4. 2005 High

    Whether MDMX (MDM4) is also regulated by USP7 was unknown; demonstration that USP7 deubiquitinates MDMX and that ATM-dependent phosphorylation reduces MDMX-USP7 affinity after DNA damage integrated USP7 into the DNA damage signaling cascade controlling the entire MDM2/MDMX/p53 network.

    Evidence Co-IP; in vitro deubiquitination; DNA damage treatments showing phosphorylation-dependent affinity change

    PMID:15916963

    Open questions at the time
    • Identity of the kinase and phosphatase directly acting on USP7 itself not yet known
    • Whether USP7-MDMX interaction occurs through the TRAF domain was not structurally resolved
  5. 2006 High

    The structural basis for substrate recognition was established by co-crystal structures showing that the USP7 TRAF domain binds P/AxxS motifs in p53 and MDM2 through a pocket centered on Trp165, explaining how the same surface mediates mutually exclusive substrate and viral protein binding.

    Evidence X-ray co-crystal structures of USP7 TRAF domain with p53, MDM2, and EBNA1 peptides; Trp165 mutagenesis

    PMID:16474402

    Open questions at the time
    • How USP7 achieves substrate selectivity beyond the P/AxxS motif was unknown
    • Full-length USP7 structure with substrate not determined
  6. 2006 High

    Whether USP7 regulates substrates beyond the p53 axis was unclear; its deubiquitination of FOXO4 in response to oxidative stress — regulating transcriptional activity rather than protein stability — revealed a non-degradative role for USP7-mediated deubiquitination.

    Evidence Co-IP; in vivo deubiquitination; transcriptional reporter assays; subcellular fractionation in human cells

    PMID:16964248

    Open questions at the time
    • The ubiquitin chain type removed from FOXO4 was not identified
    • Whether this extends to other FOXO family members was untested
  7. 2008 High

    The role of USP7 in controlling protein localization was demonstrated by showing that USP7 deubiquitinates PTEN to reduce its nuclear import, with PML bodies and DAXX opposing this activity; this established USP7 as a regulator of tumor suppressor subcellular distribution.

    Evidence In vitro/in vivo deubiquitination; subcellular fractionation; siRNA; rescue with retinoic acid/arsenic trioxide in multiple cell systems

    PMID:18716620

    Open questions at the time
    • Whether USP7-PTEN interaction is direct or mediated by adaptor was ambiguous
    • Ubiquitin linkage type on PTEN not determined
  8. 2009 High

    In vivo essentiality of USP7 was established: Hausp knockout is embryonic lethal at E6.5–E7.5, partially rescued by p53 deletion, confirming that USP7 has both p53-dependent and p53-independent essential developmental functions.

    Evidence Conventional and conditional knockout mice; genetic epistasis with p53 double knockout

    PMID:19946331

    Open questions at the time
    • The p53-independent essential functions were not molecularly identified
    • Tissue-specific requirements for USP7 not systematically explored
  9. 2011 High

    How USP7 catalytic activity is regulated was resolved: crystal structures showed the C-terminal HUBL-45 di-Ubl unit activates USP7 ~100-fold by remodeling a switching loop in the catalytic domain, and GMPS binding to HUBL-123 allosterically hyperactivates the enzyme, establishing a multi-layered intramolecular activation mechanism.

    Evidence Crystal structure of HUBL C-terminal domain; fold-activation kinetics; deletion mapping; GMPS binding experiments

    PMID:21981925

    Open questions at the time
    • How GMPS is itself regulated to control USP7 hyperactivation in vivo was unknown
    • Whether other co-activators exist was not explored
  10. 2011 High

    USP7's substrate repertoire was extended to neural biology: USP7 deubiquitinates REST via its P/AxxS motif and maintains REST levels in neural progenitor cells, linking USP7 to stem cell maintenance and differentiation.

    Evidence Co-IP; shRNA knockdown; rescue with REST overexpression; P/AxxS mutagenesis in REST

    PMID:21258371

    Open questions at the time
    • Whether USP7-REST axis operates in adult neurogenesis was untested
    • Other DUBs potentially redundant with USP7 for REST not identified
  11. 2012 High

    How DNA damage signals reach USP7 was clarified: CK2 phosphorylates USP7 at Ser18 to stabilize it (maintaining MDM2 and low p53), while ATM-activated PPM1G dephosphorylates Ser18 after irradiation to destabilize USP7, establishing USP7 as a phosphorylation-regulated switch in the DNA damage response.

    Evidence MS identification of Ser18; kinase/phosphatase assays; siRNA of PPM1G; IR treatment with western blot for USP7/MDM2/p53

    PMID:22361354

    Open questions at the time
    • Whether additional phosphorylation sites regulate USP7 was not systematically examined
    • The E3 ligase targeting dephosphorylated USP7 for degradation was not identified at this stage
  12. 2015 High

    USP7's role in DNA damage tolerance was expanded: deubiquitination of Rad18 and RNF168 maintains PCNA monoubiquitination, translesion synthesis, and ubiquitin-dependent DNA damage signaling (53BP1/BRCA1 recruitment), positioning USP7 as a central regulator of multiple DNA repair pathways.

    Evidence In vitro/in vivo deubiquitination of Rad18 and RNF168; PCNA ubiquitination; Polη foci; immunofluorescence of 53BP1/BRCA1 foci; rescue experiments

    PMID:25894431 PMID:25961918

    Open questions at the time
    • Whether USP7 coordinates Rad18 and RNF168 at the same damage site was untested
    • Redundancy with other DUBs in DNA damage signaling not fully explored
  13. 2015 High

    USP7's developmental signaling roles were broadened: USP7 deubiquitinates Ci/Gli to promote Hedgehog signaling (conserved Drosophila-to-mammal), and stabilizes Cry1 after genotoxic stress to shift circadian clock phase, revealing USP7 as a stress-responsive node connecting DNA damage to developmental and circadian pathways.

    Evidence Drosophila genetics and mammalian Gli ubiquitination assays; Hh pathway reporters; Cry1 co-IP and circadian phase assays after DNA damage

    PMID:25756610 PMID:26120032

    Open questions at the time
    • Whether USP7-Cry1 interaction is direct or via an adaptor was not fully resolved
    • The physiological importance of USP7-Hedgehog regulation in mammalian development was untested in vivo
  14. 2016 High

    USP7's role in hypoxic signaling and epigenetics was revealed: USP7 deubiquitinates HIF-1α, and K63-polyubiquitination of USP7 at K443 by HectH9 enables interaction with the ubiquitin receptor CBP to mediate H3K56 acetylation at HIF target gene promoters, establishing a non-canonical catalytic-plus-scaffolding function.

    Evidence Co-IP; ChIP-seq; K443R mutant; EMT assays in hypoxic conditions

    PMID:27934968

    Open questions at the time
    • Whether K63-polyubiquitinated USP7 retains deubiquitinase activity was not directly tested
    • The generality of K63-Ub-mediated USP7 scaffolding beyond HIF-1α targets was unknown
  15. 2017 High

    Druggability of USP7 was structurally established: co-crystal structures revealed a novel allosteric binding site distinct from the active site, enabling development of highly selective inhibitors with IC50 < 10 nM, transforming USP7 from a biological target into a tractable therapeutic target.

    Evidence Co-crystal X-ray structures with small-molecule inhibitors; biochemical IC50 and cellular EC50 profiling

    PMID:29200206

    Open questions at the time
    • In vivo pharmacokinetics and therapeutic window not established in this study
    • Whether allosteric inhibition affects all substrates equally was unknown
  16. 2019 High

    USP7's role in Hippo signaling was established: USP7 deubiquitinates and stabilizes Yorkie/YAP in a conserved Drosophila-to-mammalian mechanism, and also regulates cytokinesis through FBXO38-KIF20B stabilization, expanding USP7 functions to growth control and cell division.

    Evidence Co-IP and in vivo deubiquitination in Drosophila and mammalian cells; AP-MS/BioID identification of FBXO38; cytokinesis rescue experiments

    PMID:30679505 PMID:30804394

    Open questions at the time
    • Whether USP7 regulation of YAP/TAZ is Hippo kinase-dependent or independent was debated
    • The link between USP7-mediated cytokinesis control and its other cell cycle functions was unclear
  17. 2021 High

    USP7's chromatin and epigenetic functions were deepened: USP7 deubiquitinates both EZH2 (stabilizing PRC2) and H2BK120ub1 (enabling PRC2 chromatin loading), while also supporting PP2A-mediated CDK1 regulation; this established USP7 as a dual regulator of Polycomb repression and cell cycle kinase signaling.

    Evidence ChIP-seq; in vivo deubiquitination of EZH2 and H2B; phosphoproteomics identifying widespread CDK1 substrate hyperphosphorylation upon USP7 inhibition; PP2A/CDK1 inhibitor rescue

    PMID:33849069 PMID:33856059

    Open questions at the time
    • Whether PP2A is a direct deubiquitination substrate of USP7 or is indirectly regulated was not resolved
    • How USP7 coordinates its PRC2 and cell cycle functions temporally was unclear
  18. 2022 High

    Systematic identification of USP7 substrates and a second allosteric druggable site were achieved: proteome-wide analysis identified ~20 high-confidence substrates including MGA and PHIP, while co-crystal structures revealed a covalent allosteric site at Cys576 in the HUBL domain, expanding both the substrate network and pharmacological strategies.

    Evidence Label-free quantitative proteomics of USP7 KO cells; co-crystal structure of HUBL domain with eupalinolide B at Cys576; in vivo neuroinflammation model validation

    PMID:35947662 PMID:36302555

    Open questions at the time
    • Many proteomically identified substrates lack individual biochemical validation
    • Whether HUBL-site and catalytic-site inhibitors have synergistic or distinct cellular effects was untested
  19. 2024 High

    USP7's oncogenic substrate range was extended to KRAS: USP7 removes K48-linked polyubiquitin from KRAS K147, stabilizing both wild-type and oncogenic mutant KRAS, and USP7 inhibitors overcome KRAS-G12C inhibitor resistance, establishing a new therapeutic rationale for USP7 targeting in RAS-driven cancers.

    Evidence Co-IP; in vivo deubiquitination with K147 mutant; TRAF domain mapping; drug resistance assays in NSCLC cells

    PMID:39499616

    Open questions at the time
    • Whether USP7 regulates other RAS family members was not tested
    • In vivo therapeutic efficacy of USP7 inhibition in KRAS-driven tumors not yet shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive substrate cataloging, the mechanisms by which USP7 achieves substrate prioritization in vivo — particularly how signaling inputs (phosphorylation, K63-ubiquitination, co-activator binding) redirect USP7 among its many substrates in different cellular contexts — remain unresolved.
  • No integrated quantitative model of substrate competition and prioritization exists
  • Full-length USP7 structure in complex with a complete substrate has not been determined
  • Tissue-specific and context-dependent substrate hierarchies are largely unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 14 GO:0016787 hydrolase activity 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3 R-HSA-1266738 Developmental Biology 1 R-HSA-4839726 Chromatin organization 1 R-HSA-69306 DNA Replication 1 R-HSA-9612973 Autophagy 1
Partners
DAXXEZH2GMPSMCM-BPMDM2MDMXPTENTP53
Complex memberships
USP7-GMPSUSP7-MDM2-p53USP7-PRC2

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 USP7/HAUSP directly deubiquitinates p53 both in vitro and in vivo, stabilizing it against Mdm2-mediated proteasomal degradation; catalytically inactive USP7 mutant increases p53 ubiquitination and destabilizes p53 Affinity purification/mass spectrometry to identify p53-USP7 interaction; in vitro and in vivo deubiquitination assays; catalytic-dead mutant overexpression Nature High 11923872
2004 USP7/HAUSP deubiquitinates and stabilizes Mdm2 in a p53-independent manner; near-complete ablation of HAUSP destabilizes Mdm2 (via self-ubiquitination), indirectly activating p53, revealing a dynamic feedback loop RNAi knockdown of endogenous HAUSP; western blot analysis of p53 and Mdm2 levels; HeLa cell controls Molecular cell High 15053880
2005 HAUSP interacts with Hdmx (MDM4), directly deubiquitinating and stabilizing it; HAUSP activity is required to maintain normal Hdmx levels; DNA damage-induced ATM-dependent phosphorylation of Hdmx/Hdm2 reduces their affinity for HAUSP, leading to their destabilization Co-immunoprecipitation; in vitro deubiquitination assay; RNAi knockdown; DNA damage treatments Molecular cell High 15916963
2006 The N-terminal TRAF-like domain of USP7 binds two closely spaced 4-residue P/AXXS motifs in p53 (residues 359-367) and MDM2 (residues 147-159), with the same surface also used by EBNA1; Trp165 in the USP7 binding pocket is crucial for all peptide interactions; co-crystal structures of USP7 TRAF domain with p53 and MDM2 peptides determined Co-crystal X-ray structures of USP7 TRAF domain with p53 and MDM2 peptides; mutagenesis; tryptophan fluorescence binding assays Nature structural & molecular biology High 16474402
2006 USP7/HAUSP interacts with and deubiquitinates FOXO4 in response to oxidative stress; this deubiquitination does not affect FOXO4 protein half-life but negatively regulates FOXO4 transcriptional activity; FOXO monoubiquitination in response to oxidative stress promotes its nuclear re-localization Co-immunoprecipitation; in vivo deubiquitination assay; luciferase transcriptional reporter assays; nuclear/cytoplasmic fractionation Nature cell biology High 16964248
2007 A trimeric complex of p53, Mdm2, and HAUSP can exist in vivo despite mutually exclusive p53/Mdm2 binding to the HAUSP TRAF domain; HAUSP can deubiquitinate p53 in trans using Mdm2 as a bridging molecule; p53 mutant lacking HAUSP binding is degraded by Mdm2 but HAUSP can still antagonize Mdm2-mediated ubiquitination via this trans mechanism In vitro binding assays with p53 HAUSP-binding mutant; co-immunoprecipitation in vivo; in vitro ubiquitination assays Oncogene High 17525743
2008 HAUSP/USP7 deubiquitinates PTEN, reducing its nuclear import; PML nuclear bodies oppose HAUSP activity toward PTEN through the adaptor protein DAXX, thereby promoting PTEN nuclear localization; disruption of PML function (e.g., by PML-RARα) leads to aberrant PTEN nuclear exclusion via unchecked HAUSP activity Co-immunoprecipitation; in vitro and in vivo deubiquitination assays; subcellular fractionation; siRNA knockdown; rescue experiments with retinoic acid/arsenic trioxide Nature High 18716620
2009 HAUSP knockout mice die at embryonic day E6.5-E7.5 due to p53 activation and reduced proliferation; p53 deletion partially rescues embryonic lethality, demonstrating that HAUSP-mediated p53 regulation is essential in vivo and that HAUSP also has p53-independent functions Conditional knockout mouse model; genetic epistasis (hausp/p53 double knockout); immunohistochemistry; western blot Oncogene High 19946331
2009 Small molecule HBX 41,108 inhibits USP7 deubiquitinating activity with submicromolar IC50 through an uncompetitive reversible inhibition mechanism; inhibition blocks USP7-mediated p53 deubiquitination in vitro and in cells, stabilizes p53, and induces p53-dependent apoptosis High-throughput screening; enzyme kinetics assay; in vitro and in vivo deubiquitination assays; p53 target gene transcription; cell viability in isogenic p53 WT and null lines Molecular cancer therapeutics High 19671755
2010 USP7 promotes chromatin remodeling to facilitate base excision repair of oxidative DNA lesions; USP7 knockdown reduces chromatin DNA accessibility without changing the levels or activity of BER enzymes, demonstrating that USP7 acts upstream of the repair process siRNA knockdown; chromatin accessibility assay; BER activity assay; quantification of oxidative lesion repair Nucleic acids research Medium 21138959
2011 USP7/HAUSP C-terminal region 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 to promote ubiquitin binding; GMPS binds the first three Ubl domains (HUBL-123) and allosterically hyperactivates USP7 by stabilizing the HUBL-45-activated state Crystal structure of HUBL C-terminal domain; activity assays measuring fold-activation; deletion mapping; allosteric GMPS binding experiments Molecular cell High 21981925
2011 HAUSP/USP7 deubiquitinates REST to prevent its β-TrCP-mediated proteasomal degradation, maintaining REST levels in neural progenitor cells; a consensus P/AXXS motif (310-PYSS-313) in REST is required for HAUSP-mediated deubiquitination; HAUSP knockdown decreases REST and induces NPC differentiation, rescued by REST overexpression Co-immunoprecipitation; in vivo deubiquitination assay; shRNA knockdown; rescue experiments; site-directed mutagenesis of REST HAUSP-binding motif Nature cell biology High 21258371
2011 Brain-specific hausp knockout causes neonatal lethality with brain hypoplasia due to p53-mediated apoptosis in neural cells; p53 levels and transcriptional activity are elevated in hausp-null brains; p53 deletion largely restores neural cell survival, but does not fully rescue lethality, indicating p53-independent HAUSP functions Conditional brain-specific knockout; genetic rescue with p53 knockout; immunohistochemistry; western blot; TUNEL apoptosis assay Cell death and differentiation High 21350561
2011 KSHV viral interferon regulatory factor 4 (vIRF4) inhibits HAUSP through a bilateral belt-type interaction: vif1 peptide binds the HAUSP TRAF domain blocking substrate binding; vif2 peptide simultaneously binds both the TRAF and catalytic domains to suppress deubiquitination activity Structural analysis (crystal structure); peptide binding assays; in vitro deubiquitination assay; cell-cycle arrest and apoptosis assays; xenograft tumor model Nature structural & molecular biology High 22056774
2012 ATM-dependent phosphatase PPM1G dephosphorylates USP7 at serine 18 after DNA damage; in unstressed cells, CK2 phosphorylates USP7S at Ser18, stabilizing it and thereby stabilizing Mdm2 (p53 downregulation); after ionizing radiation, PPM1G-mediated dephosphorylation destabilizes USP7S, leading to Mdm2 downregulation and p53 accumulation Mass spectrometry identification of USP7 phosphorylation; kinase/phosphatase assays; siRNA knockdown; DNA damage (ionizing radiation) treatment; western blot for USP7/Mdm2/p53 levels Molecular cell High 22361354
2013 USP7 directly interacts with MCM-BP via the (155)PSTS(158) sequence that contacts the TRAF domain binding pocket; USP7 and MCM-BP tether USP7 to MCM proteins on chromatin; USP7 loss causes accumulation of MCM proteins on chromatin in mid-to-late S phase due to defective MCM unloading, without affecting fork rate or origin firing Co-immunoprecipitation; structural analysis of USP7-MCM-BP interaction; USP7 knockout cells; BrdU incorporation/DNA fiber assays; chromatin fractionation Molecular and cellular biology High 24190967
2014 USP7 directly deubiquitinates and stabilizes Chk1; USP7 depletion/inhibition lowers Chk1 protein levels; wild-type but not catalytic-mutant USP7 increases Chk1 half-life and deubiquitinates Chk1 in vivo and in vitro; this effect is independent of USP7's known regulation of Claspin In vitro and in vivo deubiquitination assays; USP7 knockdown/inhibition; catalytic-dead mutant overexpression; pulse-chase half-life assay; rescue with Claspin overexpression Cell cycle High 25483066
2015 USP7/HAUSP deubiquitinates and stabilizes Cry1 in response to genotoxic stress, shifting circadian clock time; Hausp interacts with Cry1 following DNA damage (genotoxic stress induces Cry1 phosphorylation and its deubiquitination by Hausp) Co-immunoprecipitation; in vivo deubiquitination; genotoxic stress treatments; circadian clock phase assays; genetic knockouts eLife High 25756610
2015 Usp7/HAUSP deubiquitinates and stabilizes Ci/Gli transcription factors, positively regulating Hedgehog signaling; Hh stimulation promotes Usp7 binding to Ci; Usp7 forms a complex with GMPS to promote Hh pathway activity; the mammalian counterpart HAUSP similarly stabilizes Gli by modulating its ubiquitination Co-immunoprecipitation; in vivo ubiquitination assay; Drosophila genetics; mammalian Gli ubiquitination assay; pathway reporter assays Developmental cell High 26120032
2015 USP7 binds RNF168 directly in vitro and in vivo, deubiquitinates RNF168, and protects it from UV-induced degradation; loss of USP7 impairs H2A monoubiquitination and recruitment of BRCA1 and 53BP1 to DNA damage foci; RNF168 restoration rescues ubiquitin-dependent DNA damage signaling in USP7-disrupted cells Co-immunoprecipitation; in vivo deubiquitination; immunofluorescence foci assays; rescue with RNF168 overexpression Cell cycle High 25894431
2015 USP7 directly interacts with Rad18 via a consensus USP7-binding motif; USP7 deubiquitinates poly-ubiquitin chains from Rad18 in vitro and in vivo; USP7 depletion destabilizes Rad18, compromising UV-induced PCNA monoubiquitination, Polη recruitment to stalled forks, and DNA damage tolerance Co-immunoprecipitation; in vitro and in vivo deubiquitination; siRNA knockdown; DNA fiber/PCNA ubiquitination assays; Polη foci assay Oncogene High 25961918
2016 HAUSP/USP7 deubiquitinates HIF-1α to increase its stability and promote epithelial-mesenchymal transition; hypoxia induces K63-linked polyubiquitination of HAUSP at lysine 443, enhancing its functions; K63-polyubiquitinated HAUSP interacts with the ubiquitin receptor CBP to specifically mediate H3K56 acetylation on HIF-1α target gene promoters; HectH9 is the E3 ligase for HAUSP Co-immunoprecipitation; in vivo deubiquitination assay; ChIP-seq; chromatin immunoprecipitation; mutant HAUSP (K443R); EMT assays Nature communications High 27934968
2016 Trip12 is an E3 ubiquitin ligase for USP7; Trip12 ubiquitinates USP7 to control its protein stability; Trip12 knockdown increases USP7 levels and mimics USP7 overexpression (G1 arrest), while Trip12 overexpression phenocopies USP7 knockdown (S phase increase) Co-immunoprecipitation; in vivo ubiquitination assay; siRNA knockdown; cell cycle analysis FEBS letters Medium 27800609
2017 Co-crystal structures of human USP7 complexed with small-molecule inhibitors reveal a previously undisclosed allosteric binding site distinct from the active site; inhibitors with IC50 < 10 nM and high selectivity were identified; cancer cell lines with EC50 < 30 nM sensitivity to USP7 inhibition identified Co-crystal X-ray structures of USP7 with inhibitors; biochemical IC50 assays; cellular EC50 assays; selectivity profiling Nature chemical biology High 29200206
2017 USP7 regulates Wnt/β-catenin signaling by preventing ubiquitination and degradation of β-catenin; USP7 inhibition by P5091 leads to enhanced ubiquitination and degradation of β-catenin, attenuating Wnt pathway activity USP7 knockdown/inhibitor (P5091); ubiquitination assay of β-catenin; Wnt reporter assays; xenograft tumor growth assay Biochemical pharmacology Medium 28216017
2017 USP7 stabilizes HIV-1 Tat protein through deubiquitination; USP7 specific inhibitor or CRISPR-Cas9 deletion of USP7 reduces Tat protein and viral production; HIV-1 infection upregulates endogenous USP7 protein levels USP7 inhibitor (P5091)/CRISPR-Cas9 KO; co-immunoprecipitation; in vivo deubiquitination; viral production assay The Biochemical journal Medium 28280111
2017 USP7 C-terminal domain (independent of deubiquitylation activity) promotes p53 sequence-specific DNA binding via interaction with the p53 C-terminal regulatory region; catalytically inactive USP7 promotes p53 binding to target sequences and p21 expression in cells without increasing p53 protein levels In vitro DNA binding/EMSA assay; domain-deletion and catalytic-mutant overexpression; p21 luciferase reporter; ChIP assay PloS one Medium 20885946
2017 USP7 selectively modulates conformational states of its catalytic domain for activation; electrostatic interactions in the distal 'switching loop' region and local packing in the hydrophobic core mediate conformational changes controlling USP7 catalytic domain activation, as validated by engineered variants with improved activity Comparative structural analysis; molecular dynamics simulations; RosettaDesign sequence re-engineering; multiple X-ray crystal structures; kinetic analysis Structure High 29249604
2018 USP7 interacts with USP11, PPM1G, TRIP12, DDX24 (via TRAF domain binding pocket), and DHX40 (via Ubl2 domain) in gastric carcinoma cells; USP7 consistently stabilizes DDX24, DHX40 and TRIP12 in a catalytic-activity-dependent manner; P/A/ExxS motifs in USP11 and DDX24 are critical for USP7 binding Affinity purification coupled to mass spectrometry; USP7 binding-pocket mutants; USP7 expression modulation; USP7 inhibitor treatment; P/AxxS motif mutagenesis Scientific reports High 30367141
2018 HAUSP inhibition combined with Nutlin-3 synergistically activates p53 and induces p53-dependent apoptosis; HAUSP also targets N-Myc oncoprotein in a p53-independent manner, and HAUSP inhibitors suppress N-Myc activities in p53-mutant cells USP7 inhibitors + Nutlin-3 combination; cell viability/apoptosis assays; N-Myc co-immunoprecipitation and stability assays Cell cycle Medium 29616860
2019 Usp7 deubiquitinates and stabilizes the Hippo pathway effector Yorkie (Yki) in Drosophila; Hippo signaling activation attenuates Usp7-Yki binding; the mammalian homolog HAUSP similarly regulates YAP ubiquitination and degradation; HAUSP and YAP expression are positively correlated in hepatocellular carcinoma Co-immunoprecipitation; in vivo ubiquitination assay; Drosophila genetics; YAP ubiquitination assay in mammalian cells Nature communications High 30679505
2019 USP7 interacts with and deubiquitinates NOTCH1 in T-ALL cells; USP7 knockdown increases NOTCH1 ubiquitination and reduces its protein level; the MATH and UBL domains of USP7 mediate the NOTCH1 interaction Co-immunoprecipitation; in vivo and in vitro deubiquitination assays; siRNA knockdown; domain mapping Signal transduction and targeted therapy High 30370059
2019 USP7 deubiquitinates and stabilizes Maf proteins (c-Maf, MafA, MafB) in myeloma cells; USP7 interaction with Maf proteins blocks their polyubiquitination and degradation; USP7 knockdown results in Maf protein degradation with increased polyubiquitination; USP7-enhanced Maf transcriptional activity promotes myeloma survival Co-immunoprecipitation/MS; in vivo deubiquitination assay; siRNA knockdown; luciferase reporter for Maf transcriptional activity; cell viability assays The Journal of biological chemistry Medium 31822558
2020 USP7 deubiquitinates and stabilizes PD-L1 in gastric cancer cells; USP7 directly interacts with PD-L1; abrogation of USP7 attenuates PD-L1/PD-1 interaction and sensitizes cancer cells to T cell killing Co-immunoprecipitation; in vivo deubiquitination assay; siRNA knockdown/USP7 inhibitor; T cell killing assay in vitro and in vivo Acta pharmaceutica Sinica. B Medium 33777676
2020 USP7 deubiquitinates the E3 ubiquitin ligase NEDD4L; NEDD4L mediates SMAD2 degradation; USP7 stabilization of NEDD4L thereby activates SMAD2-dependent autophagy and clearance of misfolded proteins; inhibition of USP7 protects against proteotoxicity in mammalian neurons and ALS model organisms Genome-wide C. elegans screen; conservation validated in Drosophila and mammalian cells; co-immunoprecipitation; in vivo deubiquitination assay; autophagy flux assays Proceedings of the National Academy of Sciences of the United States of America High 33106424
2020 USP7 interacts with USP7 and deubiquitinates and stabilizes ZNF638; USP7 also facilitates transcription of ZNF638 via stabilization of CREB; the USP7/ZNF638 axis promotes de novo lipogenesis through AKT/mTORC1/S6K-dependent SREBP1C cleavage Co-immunoprecipitation; in vivo deubiquitination assay; ChIP; gene expression analysis; liver steatosis mouse model with USP7/ZNF638 knockdown Cell death & disease Medium 33040080
2021 USP7 inhibition/depletion leads to widespread CDK1 activation throughout the cell cycle, causing DNA damage and cell toxicity; USP7 interacts with PP2A phosphatase and supports its active localization in the cytoplasm; USP7 inhibition broadly increases phosphorylation of CDK1 targets; CDK1 inhibition or PP2A activation alleviates USP7 inhibitor toxicity Co-immunoprecipitation (USP7-PP2A); phosphoproteomics; CDK1 inhibitor rescue; PP2A chemical activation rescue; DNA replication and damage assays The EMBO journal High 33856059
2021 USP7 preferentially interacts with polyQ-expanded androgen receptor (AR) and directly deubiquitinates AR; USP7 knockdown reduces mutant AR aggregation and cytotoxicity; monoallelic Usp7 knockout ameliorates motor phenotypes in transgenic SBMA mice; quantitative proteomics identified specific ubiquitinated lysine residues on mutant AR regulated by USP7 Quantitative proteomics; co-immunoprecipitation; in vivo deubiquitination assay; SBMA mouse model; Drosophila genetics; cell cytotoxicity assays The Journal of clinical investigation High 33170804
2021 USP7 deubiquitinates and stabilizes BCR-ABL fusion protein; USP7 interacts with BCR-ABL and blocks its polyubiquitination; USP7 knockdown/inhibition triggers BCR-ABL degradation and suppresses downstream signaling; artesunate inhibits USP7/BCR-ABL interaction, promoting BCR-ABL degradation DUB panel screen; co-immunoprecipitation; in vivo ubiquitination assay; siRNA knockdown; USP7 inhibitor; cell apoptosis assay Cell death & disease Medium 33963175
2021 USP7 deubiquitinates and stabilizes EZH2 as part of a PRC2 complex; USP7 also deubiquitinates H2BK120ub1, which is required for chromatin loading of PRC2 and subsequent H3K27 trimethylation; USP7/PRC2 complex transcriptionally represses FOXO1 and other genes to drive cancer cell proliferation Co-immunoprecipitation; in vivo deubiquitination assay; ChIP-seq; genome-wide transcriptional target analysis; cancer cell proliferation and tumorigenesis assays Nucleic acids research High 33849069
2022 A small molecule (eupalinolide B) covalently and allosterically targets Cys576 in the non-catalytic HUBL domain of USP7; this binding inhibits USP7, causing ubiquitination-dependent degradation of Keap1 and subsequent Nrf2-dependent anti-neuroinflammation gene transcription in microglia; co-crystal structure confirms the allosteric HUBL binding site Co-crystal structure of USP7 HUBL domain with inhibitor; covalent modification assay (MS); Keap1 ubiquitination assay; Nrf2 reporter assay; in vivo neurodegeneration mouse model Science advances High 35947662
2022 USP7 deubiquitinates and stabilizes TAZ (a Hippo effector) in HNSCC by selectively removing K48-linked ubiquitination chains, antagonizing β-TRCP-mediated degradation and enhancing nuclear retention and transcriptional output; this is independent of canonical Hippo kinase cascade siRNA/cDNA library deubiquitinase screen; co-immunoprecipitation; in vivo deubiquitination assay; nuclear fractionation; xenograft and PDX models Cell death & disease Medium 35931679
2022 USP7 deubiquitinates Raf-1 by binding to the PVDS motif (CR2 region) via its TRAF domain, removing M1-, K6-, K11-, K27-, K33-, and K48-linked polyubiquitin chains from Raf-1; deubiquitination by USP7 decreases Raf-1 threonine phosphorylation and inhibits ERK1/2 signaling, thereby inhibiting G2/M transition and lung adenocarcinoma cell proliferation Bioinformatics binding-motif analysis; co-immunoprecipitation; in vivo deubiquitination assay; phosphorylation assay; ERK1/2 signaling assay; cell cycle analysis Cell death & disease Medium 35948545
2022 USP7 interacts with and deubiquitinates ABCB1 (MDR1), stabilizing it to promote chemoresistance in triple-negative breast cancer; USP7 overexpression increases ABCB1 stability and chemoresistance while USP7 knockdown reduces ABCB1 levels Co-immunoprecipitation; in vivo deubiquitination assay; siRNA knockdown; drug sensitivity assays Cells Medium 36291159
2022 USP7 depletion induces cellular senescence in melanoma; RRM2 is a USP7 substrate regulated specifically during S phase of the cell cycle; ectopic RRM2 expression rescues the senescent phenotype caused by USP7 depletion In vivo dropout screens in PDX models; transcriptomics; proteomics; co-immunoprecipitation; RRM2 rescue experiments; senescence assays Cell reports Medium 36130505
2022 USP7 inhibits osteoclastogenesis by impairing K63-linked polyubiquitination of TRAF6, suppressing NF-κB and MAPK activation downstream of RANKL without affecting TRAF6 stability; USP7 also protects STING from degradation, inducing IFN-β to cooperatively inhibit osteoclastogenesis Co-immunoprecipitation; in vivo ubiquitination assay (K63-linkage specific); NF-κB/MAPK activity assays; STING stability assay; in vitro and in vivo osteoclast differentiation assays; OVX mouse model Aging and disease Medium 37199589
2022 Proteome-wide analysis revealed 20 high-confidence USP7 substrates; MGA and PHIP were experimentally validated as novel substrates; MGA deletion reduced cell proliferation similarly to USP7 deletion; USP7 and its closest homolog USP47 show both overlapping and distinct substrate profiles Label-free quantitative proteomics of USP7/USP47 single/double KO cells; transcriptomics; tandem affinity purification; in vivo deubiquitination assay Genes & development High 36302555
2024 USP7 directly deubiquitinates KRAS by binding via its TRAF domain and removing K48-linked polyubiquitin chains from KRAS residue K147, stabilizing KRAS and promoting NSCLC cell proliferation; USP7 also stabilizes oncogenic KRAS mutants through deubiquitination; USP7 inhibitors suppress KRAS-G12C inhibitor-resistant NSCLC cells Co-immunoprecipitation; in vivo deubiquitination assay; site-specific K147 mutant; TRAF domain mapping; cell proliferation assays; drug resistance assays Cell reports High 39499616
2024 USP7 deubiquitinates and stabilizes KDM5B; deletion of USP7 increases sensitivity to cisplatin by disrupting KDM5B stability; KDM5B inhibits ZBTB16 expression by reducing H3K4me3 at the ZBTB16 promoter, which increases TOP2A expression to confer cisplatin resistance Co-immunoprecipitation; in vivo deubiquitination assay; ChIP-seq (H3K4me3); USP7 siRNA knockdown; cisplatin sensitivity assays in vitro and in vivo Cell death and differentiation Medium 38287116
2003 EBNA1 (Epstein-Barr virus) binds USP7 through its N-terminal TRAF-like domain (same domain that binds p53); ICP0 (HSV-1) binds a distinct C-terminal domain (residues 599-801) of USP7; purified USP7 is monomeric and active for cleaving ubiquitin from EBNA1; EBNA1 peptide (residues 395-450) competes with p53 peptide for USP7 binding with ~10-fold higher affinity Affinity chromatography; MALDI-TOF domain mapping; tryptophan fluorescence binding assays; gel filtration competition assay; deubiquitination assay The Journal of biological chemistry High 14506283
2015 USP7 interacts with and stabilizes HAUSP-target REST through deubiquitination and promotes maintenance of neural progenitor cells (NPC); USP7 deubiquitinates HAUSP-binding substrate nucleolin via a complex containing p53 and Mdm2; Mdm2 and p53 are required for HAUSP-nucleolin interaction; DNA damage (irradiation) increases HAUSP-nucleolin interaction leading to nucleolin stabilization Proteomic analysis; co-immunoprecipitation; in vivo deubiquitination assay; HAUSP binding motif mutagenesis on nucleolin Scientific reports Medium 26238070
2016 USP7 acts as a SUMO deubiquitinase (SDUB) at replication forks by deubiquitinating SUMOylated proteins; this novel mechanism contributes to control of DNA replication Biochemical fractionation; deubiquitination assay on SUMOylated substrates (reviewed in BioEssays based on primary research) BioEssays Low 27374980
2019 USP7 regulates cytokinesis through stabilization of FBXO38, which in turn stabilizes KIF20B (a Kinesin-6 required for cytokinesis); USP7 depletion reduces FBXO38 and KIF20B levels and KIF20B at the midbody, leading to cytokinetic defects; rescue of cytokinetic defects by restoring FBXO38 or KIF20B establishes this pathway Affinity purification-mass spectrometry; BioID proximity labeling; co-immunoprecipitation; siRNA depletion; cytokinesis assay (midbody imaging); rescue with FBXO38/KIF20B Scientific reports High 30804394
2020 USP7 inhibition (siRNA or inhibitor) in M2 macrophages leads to phenotypic reprogramming toward M1 via activation of the p38 MAPK pathway; USP7 is highly expressed in M2 but not M1 macrophages; USP7 inhibition increases PD-L1 expression in tumor cells siRNA screening of 51 DUB genes in macrophages; flow cytometry; western blotting for p38 MAPK activation; in vivo Lewis lung carcinoma model Theranostics Medium 32802195
2023 PRMT5-mediated methylation (R468me2) of G3BP2 enhances its binding to USP7, promoting USP7-mediated deubiquitination and stabilization of G3BP2; PRMT5 depletion or inhibition attenuates USP7-induced G3BP2 deubiquitination; stabilized G3BP2 activates ACLY to drive de novo lipogenesis and tumorigenesis Co-immunoprecipitation; in vivo deubiquitination assay; methylation-site mutant (R468K); ACLY activity assay; lipogenesis assays Cell death & disease Medium 36878903
2024 USP7 deubiquitinates and stabilizes PRDM1 transcription factor; USP7-stabilized PRDM1 transcriptionally activates FGL1, which suppresses CD8+ T cell activity via LAG3 pathway; USP7 is itself transcriptionally activated by PRDM1 (positive feedback loop); P5091 USP7 inhibitor breaks this loop, enhancing CD8+ T cell activity Co-immunoprecipitation; in vivo deubiquitination assay; ChIP assay; luciferase reporter; siRNA knockdown; T cell killing assay; xenograft immunocompetent mouse model Acta pharmacologica Sinica Medium 38589688

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature 861 11923872
2004 A dynamic role of HAUSP in the p53-Mdm2 pathway. Molecular cell 562 15053880
2008 The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature 453 18716620
2006 FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nature cell biology 405 16964248
2009 Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Molecular cancer therapeutics 275 19671755
2006 Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nature structural & molecular biology 259 16474402
2020 USP7 targeting modulates anti-tumor immune response by reprogramming Tumor-associated Macrophages in Lung Cancer. Theranostics 230 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 224 22520753
2011 Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase. Molecular cell 220 21981925
2003 Protein profiling with Epstein-Barr nuclear antigen-1 reveals an interaction with the herpesvirus-associated ubiquitin-specific protease HAUSP/USP7. The Journal of biological chemistry 190 12783858
2017 Discovery and characterization of highly potent and selective allosteric USP7 inhibitors. Nature chemical biology 173 29200206
2009 Inactivation of HAUSP in vivo modulates p53 function. Oncogene 155 19946331
2019 USP7: Structure, substrate specificity, and inhibition. DNA repair 154 30807924
2003 Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP. The Journal of biological chemistry 148 14506283
2011 Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells. Nature cell biology 137 21258371
2018 Emerging insights into HAUSP (USP7) in physiology, cancer and other diseases. Signal transduction and targeted therapy 135 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
2005 ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell cycle (Georgetown, Tex.) 118 16082221
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 117 33777676
2017 USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth. Biochemical pharmacology 115 28216017
2020 Targeting USP7-Mediated Deubiquitination of MDM2/MDMX-p53 Pathway for Cancer Therapy: Are We There Yet? Frontiers in cell and developmental biology 114 32300595
2016 K63-polyubiquitinated HAUSP deubiquitinates HIF-1α and dictates H3K56 acetylation promoting hypoxia-induced tumour progression. Nature communications 107 27934968
2015 DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization. eLife 97 25756610
2020 Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism. Scientific reports 95 32210275
2022 Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy. Science advances 87 35947662
2018 USP7: Target Validation and Drug Discovery for Cancer Therapy. Medicinal chemistry (Shariqah (United Arab Emirates)) 85 29065837
2017 Regulation of USP7: A High Incidence of E3 Complexes. Journal of molecular biology 84 28591556
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 73 22056774
2015 USP7 deubiquitinase promotes ubiquitin-dependent DNA damage signaling by stabilizing RNF168. Cell cycle (Georgetown, Tex.) 72 25894431
2020 Parthenolide inhibits ubiquitin-specific peptidase 7 (USP7), Wnt signaling, and colorectal cancer cell growth. The Journal of biological chemistry 65 32029476
2011 Roles of HAUSP-mediated p53 regulation in central nervous system development. Cell death and differentiation 64 21350561
2015 USP7 is essential for maintaining Rad18 stability and DNA damage tolerance. Oncogene 63 25961918
2013 A role for USP7 in DNA replication. Molecular and cellular biology 61 24190967
2020 The emerging nature of Ubiquitin-specific protease 7 (USP7): a new target in cancer therapy. Drug discovery today 60 33157193
2018 USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia. Signal transduction and targeted therapy 54 30370059
2022 Discovery of a Potent and Selective Degrader for USP7. Angewandte Chemie (International ed. in English) 50 35691827
2020 The USP7 protein interaction network and its roles in tumorigenesis. Genes & diseases 49 35005106
2013 Expression of HAUSP in gliomas correlates with disease progression and survival of patients. Oncology reports 48 23483195
2022 Highlights in USP7 inhibitors for cancer treatment. Frontiers in chemistry 47 36186590
2021 Targeting Ubiquitin-Specific Protease 7 (USP7) in Cancer: A New Insight to Overcome Drug Resistance. Frontiers in pharmacology 46 33967786
2017 Generation and Validation of Intracellular Ubiquitin Variant Inhibitors for USP7 and USP10. Journal of molecular biology 46 28587923
2018 Identification and Characterization of USP7 Targets in Cancer Cells. Scientific reports 45 30367141
2017 USP7 deubiquitinase controls HIV-1 production by stabilizing Tat protein. The Biochemical journal 44 28280111
2017 Synthesis and biological evaluation of thiazole derivatives as novel USP7 inhibitors. Bioorganic & medicinal chemistry letters 43 28108249
2021 Recent advances on the intervention sites targeting USP7-MDM2-p53 in cancer therapy. Bioorganic chemistry 42 34474304
2019 The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival. The Journal of biological chemistry 42 31822558
2016 Trip12 is an E3 ubiquitin ligase for USP7/HAUSP involved in the DNA damage response. FEBS letters 42 27800609
2020 USP7 mediates pathological hepatic de novo lipogenesis through promoting stabilization and transcription of ZNF638. Cell death & disease 41 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 41 33106424
2024 USP7 as an emerging therapeutic target: A key regulator of protein homeostasis. International journal of biological macromolecules 40 38382779
2018 Molecular dynamics simulation reveals the possible druggable hot-spots of USP7. Oncotarget 39 30344943
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 Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis. Cell death and differentiation 36 38287116
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
2024 Exosomal circ-0100519 promotes breast cancer progression via inducing M2 macrophage polarisation by USP7/NRF2 axis. Clinical and translational medicine 33 39107958
2022 USP7-SOX9-miR-96-5p-NLRP3 Network Regulates Myocardial Injury and Cardiomyocyte Pyroptosis in Sepsis. Human gene therapy 32 35686454
2022 USP7 regulates the ERK1/2 signaling pathway through deubiquitinating Raf-1 in lung adenocarcinoma. Cell death & disease 32 35948545
2022 USP7 Inhibitors in Cancer Immunotherapy: Current Status and Perspective. Cancers 31 36428632
2015 HAUSP-nucleolin interaction is regulated by p53-Mdm2 complex in response to DNA damage response. Scientific reports 31 26238070
2023 USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24. Cell death & disease 30 38129408
2022 Targeting the USP7/RRM2 axis drives senescence and sensitizes melanoma cells to HDAC/LSD1 inhibitors. Cell reports 30 36130505
2021 USP7 limits CDK1 activity throughout the cell cycle. The EMBO journal 30 33856059
2023 Current and future directions of USP7 interactome in cancer study. Biochimica et biophysica acta. Reviews on cancer 29 37775071
2022 The deubiquitinase USP7 promotes HNSCC progression via deubiquitinating and stabilizing TAZ. Cell death & disease 29 35931679
2019 USP7 Regulates Cytokinesis through FBXO38 and KIF20B. Scientific reports 28 30804394
2022 The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1. Oncogene 27 35821281
2021 Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis. Cell death & disease 27 33963175
2015 HAUSP regulates c-MYC expression via de-ubiquitination of TRRAP. Cellular oncology (Dordrecht, Netherlands) 27 25925205
2023 USP7-mediated ERβ stabilization mitigates ROS accumulation and promotes osimertinib resistance by suppressing PRDX3 SUMOylation in non-small cell lung carcinoma. Cancer letters 26 38097136
2022 USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1. Cells 26 36291159
2021 Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy. The Journal of clinical investigation 26 33170804
2018 TSPY1 suppresses USP7-mediated p53 function and promotes spermatogonial proliferation. Cell death & disease 26 29748603
2017 Selectively Modulating Conformational States of USP7 Catalytic Domain for Activation. Structure (London, England : 1993) 26 29249604
2024 USP7-Based Deubiquitinase-Targeting Chimeras Stabilize AMPK. Journal of the American Chemical Society 25 38597345
2022 USP7 substrates identified by proteomics analysis reveal the specificity of USP7. Genes & development 24 36302555
2021 Bimodal regulation of the PRC2 complex by USP7 underlies tumorigenesis. Nucleic acids research 24 33849069
2010 USP7/HAUSP promotes the sequence-specific DNA binding activity of p53. PloS one 24 20885946
2024 USP7 deubiquitinates KRAS and promotes non-small cell lung cancer. Cell reports 23 39499616
2023 Ubiquitin-specific protease 7 (USP7): an emerging drug target for cancer treatment. Expert opinion on therapeutic targets 23 37789645
2020 USP7 stabilizes EZH2 and enhances cancer malignant progression. American journal of cancer research 22 32064169
2020 Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance. International journal of molecular sciences 22 33207738
2023 USP7 Inhibits Osteoclastogenesis via Dual Effects of Attenuating TRAF6/TAK1 Axis and Stimulating STING Signaling. Aging and disease 20 37199589
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 18 36878903
2020 A feedforward circuit shaped by ECT2 and USP7 contributes to breast carcinogenesis. Theranostics 18 32929379
2024 Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation. Acta pharmacologica Sinica 17 38589688
2024 The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis. Cell death & disease 17 38769122
2020 USP7 regulates the proliferation and differentiation of ATDC5 cells through the Sox9-PTHrP-PTH1R axis. Bone 17 33127578
2018 Targeting HAUSP in both p53 wildtype and p53-mutant tumors. Cell cycle (Georgetown, Tex.) 17 29616860
2016 USP7/HAUSP: A SUMO deubiquitinase at the heart of DNA replication. BioEssays : news and reviews in molecular, cellular and developmental biology 16 27374980