Affinage

USP1

Ubiquitin carboxyl-terminal hydrolase 1 · UniProt O94782

Length
785 aa
Mass
88.2 kDa
Annotated
2026-04-28
100 papers in source corpus 61 papers cited in narrative 62 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP1 is a cysteine deubiquitinase that serves as a central regulator of DNA damage tolerance and repair by deubiquitinating monoubiquitinated FANCD2/FANCI and PCNA at replication forks, thereby controlling the Fanconi anemia interstrand crosslink repair pathway, translesion synthesis, and homologous recombination (PMID:15694335, PMID:19217432, PMID:30576655, PMID:38885312). USP1 requires the WD40 cofactor UAF1 (WDR48) for full catalytic activation through allosteric modulation of the catalytic histidine pKa, and substrate recognition is further specified by the USP1 N-terminus (for FANCD2) and accessory factors such as ELG1 (for PCNA) and RAD51AP1, with DNA itself serving as an allosteric activator via USP1's insert L1 domain (PMID:22439892, PMID:20147293, PMID:31253762, PMID:33619839, PMID:30456385). USP1 activity is tightly cell-cycle-regulated through APC/C(Cdh1)-mediated G1 degradation, Cdk-dependent mitotic phosphorylation, and autocleavage coupled to Spartan-mediated removal from replication forks (PMID:21768287, PMID:22101265, PMID:35365626). Beyond DNA repair, USP1 deubiquitinates diverse substrates including ID1/2/3 to block osteogenic differentiation, TBK1 and cGAS to modulate innate immune signaling, TAZ to regulate Hippo pathway output and Th17/Treg balance, and K63-linked ubiquitin on Akt to restrict PI3K signaling during starvation (PMID:21925315, PMID:29138248, PMID:38054892, PMID:36600049, PMID:32133736).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Establishing that USP1 is a catalytically active deubiquitinating enzyme resolved the basic question of whether this USP-family gene product possesses genuine protease activity.

    Evidence In vitro cleavage of Ub-beta-galactosidase fusion by recombinant USP1

    PMID:9806842

    Open questions at the time
    • No physiological substrate identified
    • No cellular function assigned
  2. 2005 High

    Identifying FANCD2 as the first physiological substrate of USP1 placed it squarely in the Fanconi anemia DNA repair pathway, explaining how monoubiquitinated FANCD2 is reversed after damage resolution.

    Evidence RNAi screen, Co-IP, chromatin colocalization, chromosomal aberration assays in human cells

    PMID:15694335

    Open questions at the time
    • Mechanism of substrate specificity unknown
    • Whether USP1 acts alone or requires cofactors unresolved
  3. 2009 High

    Mouse Usp1 knockout producing an FA-like phenotype with impaired HR and epistasis with Fancd2 confirmed USP1 as essential for proper FA pathway function in vivo, not merely redundant.

    Evidence Targeted Usp1 KO and Usp1/Fancd2 double KO in mice with crosslinker sensitivity, HR, and fertility assays

    PMID:19217432

    Open questions at the time
    • Biochemical mechanism of USP1 activation not yet defined
    • PCNA substrate role not yet genetically validated in vivo
  4. 2010 High

    Discovery that ELG1 directs the USP1-UAF1 complex specifically to PCNA without affecting FANCD2 deubiquitination revealed how a single DUB achieves substrate selectivity through adaptor proteins.

    Evidence Co-IP, siRNA, domain mapping showing ELG1 N-terminus mediates USP1-UAF1 interaction and selectively controls PCNA-Ub levels

    PMID:20147293

    Open questions at the time
    • Structural basis of ELG1-mediated substrate selection unknown
    • Whether other adaptors exist for additional substrates unresolved
  5. 2011 High

    Multiple discoveries in 2011 expanded USP1's roles beyond DNA repair: deubiquitination of ID1/2/3 controlling osteogenic differentiation, APC/C(Cdh1)-mediated G1 degradation coupling USP1 to cell-cycle-regulated PCNA ubiquitination, and promotion of HR by suppressing NHEJ collectively established USP1 as a multi-pathway regulator with tight temporal control.

    Evidence ID protein Co-IP/deubiquitination/differentiation assays; cell-cycle synchronization with non-degradable USP1 mutant; DT40 genetic epistasis with NHEJ-deficient cells

    PMID:21482670 PMID:21768287 PMID:21925315 PMID:22101265

    Open questions at the time
    • How USP1 balances multiple substrates at different cell-cycle phases not resolved
    • Cdk phosphorylation sites on USP1 and their individual contributions unclear
  6. 2012 High

    Kinetic characterization showed UAF1 activates USP1 by lowering the catalytic histidine pKa, providing the first mechanistic explanation for cofactor-dependent activation, while discovery of N-end rule degradation of the autocleavage fragment explained how USP1 self-limits its activity.

    Evidence pH-dependent kinetics and solvent isotope effects for UAF1 activation; Ntaq1-mediated deamidation of autocleavage fragment with UV sensitivity phenotype

    PMID:22439892 PMID:23159736

    Open questions at the time
    • No high-resolution structure of USP1-UAF1 complex yet
    • How autocleavage is triggered in cells unknown
  7. 2014 High

    Development of ML323 as a selective USP1-UAF1 inhibitor pharmacologically validated USP1 as essential for both the FA and TLS pathways and opened therapeutic exploration of USP1 inhibition.

    Evidence ML323 selectivity profiling, PCNA-Ub and FANCD2-Ub cellular assays, cisplatin potentiation

    PMID:24531842

    Open questions at the time
    • Structural basis of ML323 inhibition unknown at this time
    • In vivo efficacy of USP1 inhibition not yet demonstrated
  8. 2018 High

    Demonstration that USP1 is directly stimulated by fork DNA through its DNA-binding region, and that DNA-binding-deficient USP1 fails to protect replication forks, established that USP1 functions as a DNA-activated enzyme at sites of replication stress.

    Evidence DNA-binding assays, truncation mutants lacking DNA-binding domain, replication fork protection assays in BRCA1-deficient cells

    PMID:30576655

    Open questions at the time
    • Structural basis of DNA-mediated activation not resolved
    • Whether DNA stimulation applies equally to all substrates unclear
  9. 2019 High

    Biochemical reconstitution showed that efficient FANCD2 deubiquitination requires DNA binding by UAF1 (or RAD51AP1), unifying DNA sensing and substrate engagement into a coherent activation mechanism for the FA pathway.

    Evidence Reconstituted deubiquitination with DNA-binding mutants of UAF1 and RAD51AP1, cellular FANCD2-Ub assays

    PMID:31253762

    Open questions at the time
    • Relative contributions of UAF1 vs. RAD51AP1 DNA binding in vivo not quantified
  10. 2021 High

    Crystal and cryo-EM structures of USP1-UAF1 alone and bound to monoubiquitinated FANCI-FANCD2 revealed that UAF1 drives conformational changes in FANCI-FANCD2 to present the ubiquitinated lysine, while the USP1 N-terminus confers FANCD2 specificity; insert L1 acts as an autoinhibitory element relieved by UAF1 and DNA.

    Evidence X-ray crystallography, cryo-EM, mutagenesis of UAF1-FANCI interface, insert L1/L3 deletion mutants with biochemical activity assays, N-terminal chimera experiments

    PMID:30456385 PMID:33619839 PMID:33795880

    Open questions at the time
    • Full-length USP1-UAF1-DNA-PCNA complex structure not available
    • How insert L1 communicates with the active site at atomic level not fully resolved
  11. 2022 High

    Autocleavage-defective USP1 causes replication fork stalling resolved by Spartan-mediated removal, establishing a recycling mechanism that prevents USP1 from becoming a DNA-protein crosslink-like obstacle, while cryo-EM of ML323-bound USP1 revealed a cryptic hydrophobic tunnel as the inhibitor binding site.

    Evidence Super-resolution and single-molecule tracking of autocleavage mutant; cryo-EM at 2.5 Å of USP1±ML323

    PMID:35365626 PMID:36170365

    Open questions at the time
    • Whether Spartan processes autocleavage-competent USP1 under normal conditions unclear
    • Dynamics of cryptic tunnel opening not characterized
  12. 2022 High

    Genome-wide CRISPR screens identified RAD18 and UBE2K as required for USP1 dependency, and PCNA K164R rescued USP1 inhibitor sensitivity, definitively establishing that the cytotoxic mechanism of USP1 loss involves aberrant accumulation of ubiquitinated PCNA.

    Evidence CRISPR-Cas9 screens, PCNA WT vs K164R rescue, DNA synthesis assays

    PMID:36228090

    Open questions at the time
    • Which downstream effectors of PCNA-Ub cause cell death not fully resolved
    • Whether FANCD2 deubiquitination contributes to cytotoxicity in this context unclear
  13. 2024 High

    USP1 was shown to promote PRIMPOL-generated ssDNA gap accumulation expanded by MRE11/EXO1, and RAD18-dependent PCNA-Ub was confirmed as the mechanism of USP1 inhibitor synthetic lethality in BRCA1-deficient cells, completing the mechanistic link from USP1 to replication gap-driven cell death.

    Evidence ssDNA gap assays, RAD18 KD rescue, patient-derived organoid validation of USP1 inhibitor + PARP inhibitor combination

    PMID:38180818 PMID:38885312

    Open questions at the time
    • Whether ssDNA gap toxicity is the sole mechanism or synergizes with fork collapse remains open
    • Clinical translation of USP1 inhibitor combinations awaits trial data
  14. 2024 Medium

    USP1 was found to suppress cGAS-STING signaling by removing K27-linked ubiquitin from SAR1A required for STING ER-to-Golgi trafficking, while separately stabilizing cGAS itself via K48-linked deubiquitination, revealing a dual and context-dependent role in innate immune regulation.

    Evidence Chemical DUB screen, K27 and K48 linkage-specific ubiquitination assays, STING trafficking, IFN reporter, in vivo viral and radiotherapy models

    PMID:38054892 PMID:39976106

    Open questions at the time
    • How USP1 discriminates between SAR1A and cGAS under different stimuli unknown
    • Whether these innate immune functions require UAF1 not explicitly tested for SAR1A

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural understanding of how USP1-UAF1 engages PCNA on DNA, the mechanism by which USP1 selects among its growing list of substrates in different cellular contexts, and the in vivo therapeutic window of USP1 inhibitors remain open questions.
  • No structure of USP1-UAF1 bound to ubiquitinated PCNA on DNA
  • Substrate prioritization mechanism across DNA repair, differentiation, and immune contexts unresolved
  • Clinical efficacy and toxicity of USP1 inhibitors not yet established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-69306 DNA Replication 7 R-HSA-73894 DNA Repair 7 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3
Partners
ELG1FANCD2FANCIID1PCNARAD51AP1TBK1UAF1
Complex memberships
USP1-UAF1

Evidence

Reading pass · 62 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 USP1 physically associates with FANCD2 and deubiquitinates monoubiquitinated FANCD2, with both proteins colocalizing on chromatin after DNA damage; RNAi inhibition of USP1 leads to hyperaccumulation of monoubiquitinated FANCD2 and chromosomal aberrations, placing USP1 as a deubiquitinase in the Fanconi anemia pathway. RNAi library screen, Co-IP, colocalization, chromosomal aberration assay Molecular cell High 15694335
1998 Recombinant USP1 protein possesses genuine ubiquitin-specific protease (UBP) activity, correctly cleaving a Ub-beta-galactosidase fusion to produce free ubiquitin and beta-galactosidase, identifying USP1 as an active deubiquitinating enzyme. In vitro ubiquitin cleavage assay with recombinant protein Genomics High 9806842
2009 Targeted deletion of mouse Usp1 results in elevated monoubiquitinated Fancd2 in chromatin, impaired Fancd2 foci assembly, defective homologous recombination repair, and an FA-like phenotype (crosslinker hypersensitivity, male infertility, perinatal lethality); double KO of Usp1 and Fancd2 yields a more severe phenotype, placing Usp1 downstream of Fancd2 monoubiquitination in the FA pathway. Targeted gene knockout in mice, epistasis (double KO), chromatin fractionation, HR assay Developmental cell High 19217432
2011 USP1 binds, deubiquitinates, and thereby stabilizes the ID1, ID2, and ID3 inhibitor-of-differentiation proteins; USP1 knockdown in osteosarcoma cells leads to ID protein destabilization, cell-cycle arrest, and osteogenic differentiation, while ectopic USP1 in mesenchymal stem cells stabilizes IDs and inhibits osteoblastic differentiation. Co-IP, ubiquitination assay, siRNA knockdown, ectopic expression, in vivo mouse model Cell High 21925315
2010 Human ELG1 interacts with the USP1-UAF1 complex and specifically directs USP1-UAF1 to deubiquitinate PCNA; ELG1 knockdown increases PCNA monoubiquitination without affecting FANCD2 ubiquitination, and a conserved N-terminal domain of ELG1 mediates USP1-UAF1 interaction. Co-IP, siRNA knockdown, domain mapping, ubiquitination assay The Journal of biological chemistry High 20147293
2011 USP1 and its binding partner UAF1 form a complex that promotes homologous recombination (HR)-mediated double-strand break repair; loss of UAF1 in chicken DT40 cells causes sensitivity to camptothecin and PARP inhibitors that is rescued by disrupting NHEJ, indicating USP1/UAF1 promotes HR by suppressing NHEJ. Genetic KO in DT40 cells, epistasis with NHEJ-deficient cells, drug sensitivity assays Molecular and cellular biology High 21482670
2011 USP1 is degraded in G1 via APC/C(Cdh1)-mediated ubiquitination; low USP1 levels in G1 are required for PCNA monoubiquitination in response to UV damage before DNA replication, as a non-degradable USP1 mutant inhibits PCNA monoubiquitination and likely impairs translesion synthesis polymerase recruitment. Cell cycle synchronization, APC/C(Cdh1) substrate assay, USP1 mutant expression, PCNA ubiquitination assay The Journal of cell biology High 21768287
2011 USP1 depletion stimulates DDB1-dependent degradation of phosphorylated CHK1; USP1 maintains both total and phosphorylated CHK1 levels in response to genotoxic stress, partly in a monoubiquitinated FANCD2-dependent manner, establishing a feedback circuit where activated CHK1 upregulates FANCD2 monoubiquitination, which then promotes USP1-mediated CHK1 degradation. siRNA knockdown, western blot, Co-IP, genotoxic stress assays Human molecular genetics Medium 21389083
2012 The C-terminal autocleavage fragment of USP1 (Gln-Usp1(Ct)) is a physiological substrate of the Arg/N-end rule pathway, targeted for degradation through deamidation of its N-terminal glutamine by Ntaq1; the autocleaved fragments remain associated with UAF1 and retain deubiquitylase activity until Gln-Usp1(Ct) is selectively destroyed, and stabilization of this fragment decreases PCNA monoubiquitylation and increases UV sensitivity. Biochemical reconstitution, N-end rule substrate identification, mutant analysis, cellular UV sensitivity assay Molecular cell High 23159736
2012 USP1 activity is stimulated through formation of a tight complex with the WD40 repeat protein UAF1; kinetic analyses show UAF1 activates USP1 by lowering the pKa of the catalytic histidine (by 0.43 pH units), facilitating general base catalysis at neutral pH without altering ubiquitin binding affinity; the catalytic triad is C90, H593, and D751. Kinetic analysis (pH-dependent inactivation, solvent isotope effects, proton inventory), in vitro biochemical assay Biochemistry High 22439892
2012 USP1 contains two nuclear localization signals (NLSs) that mediate nuclear import of the USP1/UAF1 complex; USP1 and UAF1 form a complex in the cytoplasm that translocates to the nucleus via USP1 NLSs, and a 100 amino acid motif in USP1 mediates UAF1 binding. Nuclear relocation assay, deletion mutagenesis, cellular localization PloS one Medium 22701671
2013 CAPNS1 (calpain regulatory subunit) is required for USP1 stability; calpain stabilizes USP1 by activating Cdk5, which inhibits Cdh1 and consequently prevents APC/C(Cdh1)-mediated USP1 degradation in G1; loss of CAPNS1 increases PCNA monoubiquitination and polymerase-η loading. siRNA knockdown, western blot, chromatin fractionation, cell-cycle analysis, Cdk5/p25 rescue Molecular and cellular biology Medium 23589330
2014 The selective USP1-UAF1 inhibitor ML323 inhibits the USP1-UAF1 complex with excellent selectivity; pharmacological inhibition reveals that USP1-UAF1 deubiquitination is required for the DNA translesion synthesis and Fanconi anemia pathways in response to UV- and cisplatin-induced DNA damage, and ML323 potentiates cisplatin cytotoxicity. Chemical inhibitor (ML323), cell-based PCNA and FANCD2 ubiquitination assays, selectivity profiling Nature chemical biology High 24531842
2015 USP1 phosphorylation at S313 is not critical for PCNA deubiquitination or UAF1 binding; amino acid motif 420-520 in USP1 is necessary and sufficient for UAF1 binding (mapping to the Fingers subdomain); USP1 autocleavage occurs in cis at the G670/G671 diglycine motif and can be reduced by cancer-associated mutation L669P. Mutagenesis (S313A, S313D, deletion mutants, GG/AA, cancer-associated mutants), cell-based UAF1 binding and PCNA deubiquitination assays Molecular cancer Medium 25744535
2016 The USP1-UAF1 complex interacts with RAD51AP1 (a RAD51-interacting protein) via UAF1; USP1-UAF1 stabilizes RAD51AP1 and promotes HR repair independently of FANCD2 deubiquitination; cells expressing UAF1-interaction-deficient RAD51AP1 show increased chromosomal aberrations and persistent RAD51 foci after DNA damage. Proteomics, Co-IP, domain mapping, HR assay, RAD51 foci, chromosomal aberration assay Cell cycle (Georgetown, Tex.) Medium 27463890
2016 PDGF signaling upregulates USP1 transcription through E2F transcription factors that directly bind and activate the Usp1 promoter; USP1 then stabilizes ID2 protein, which is required for proneural glioma cell survival. Mouse model, comparative transcriptomics, ChIP (E2F binding to Usp1 promoter), USP1 KO, ID2 protein stability assay Cancer research Medium 26951930
2017 The USP1-UAF1 complex interacts with TBK1, removes its K48-linked polyubiquitination, and prevents TBK1 proteasomal degradation, thereby stabilizing TBK1 and enhancing TLR3/4- and RIG-I-induced IRF3 activation and IFN-β secretion during antiviral responses. Co-IP, ubiquitination assay, KD/KO, IFN-β reporter assay, in vivo viral infection model The Journal of experimental medicine Medium 29138248
2018 USP1 binds to and is stimulated by fork DNA; a truncated USP1 lacking its DNA-binding region is not stimulated by DNA, fails to localize to replication forks, and cannot protect replication forks; persistence of monoubiquitinated PCNA at the replication fork is the mechanism of cell death when USP1 is absent in BRCA1-deficient cells. DNA-binding assay, truncation mutants, replication fork protection assay, PCNA-Ub localization, cell viability Molecular cell High 30576655
2018 USP1 deubiquitinates and stabilizes KPNA2 (importin subunit alpha-2) protein; USP1-mediated KPNA2 stabilization is the downstream event crucial for USP1's pro-metastatic function in breast cancer cells. Co-IP, ubiquitination assay, siRNA/inhibitor-based KD, metastasis assay in mice Oncogene Medium 30531833
2018 USP1 interacts with and deubiquitinates ULK1 via K63-linked ubiquitin chains; USP1 depletion or inhibition causes ULK1 sequestration to an insoluble/aggresome fraction and inhibits canonical autophagy while promoting an alternative lysosomal-mediated degradation route. Co-IP, ubiquitination linkage assay, cell fractionation, immunofluorescence, autophagic flux assay Autophagy Medium 30335599
2018 USP1 positively regulates protein stability of ID1 and CHK1 in glioblastoma stem-like cells, and USP1 inhibition attenuates clonogenic growth and enhances radiosensitivity. shRNA knockdown, pimozide inhibitor, protein stability assay, clonogenic assay, in vivo mouse model Neuro-oncology Medium 26032834
2019 Upon platinum treatment, USP1 is phosphorylated by ATM and ATR, binds to Snail, deubiquitinates and stabilizes Snail expression, conferring platinum resistance and promoting tumor dissemination; USP1 KO or inhibition increased platinum sensitivity in a Snail-dependent manner. Co-IP, in vivo ubiquitination assay, ATM/ATR phosphorylation assay, rescue experiments with Snail overexpression, in vivo mouse model Science advances Medium 31086816
2019 Efficient FANCD2 deubiquitination by the USP1-UAF1 complex requires DNA and is dependent on DNA binding by UAF1; RAD51AP1, via its own DNA-binding activity, can substitute for UAF1 DNA binding in FANCD2 deubiquitination in reconstituted biochemical systems and in cells. Reconstituted biochemical deubiquitination assay, DNA-binding mutants of UAF1 and RAD51AP1, cellular FANCD2 deubiquitination assay Nature communications High 31253762
2019 TonEBP sequentially recruits E3 ubiquitin ligase SHPRH and then USP1 to DNA damage sites, coordinating PCNA polyubiquitination dynamics; the Rel-homology domain of TonEBP is essential for interaction with both SHPRH and USP1. Co-IP, DNA damage recruitment assay, domain mapping, PCNA polyubiquitination assay iScience Medium 31376680
2020 USP1 removes K63-linked polyubiquitin chains on Akt to restrict PI3K-Akt-FoxO signaling in mouse muscle during prolonged starvation; Dab2 is essential for recruiting Akt to a USP1-TSC1-PHLPP1 complex for deubiquitination, and USP1 depletion increases Akt ubiquitination and glucose uptake during fasting. DUB screening platform, Co-IP, mass spectrometry, ubiquitination (K63-linkage) assay, in vivo mouse muscle USP1 depletion EMBO reports Medium 32133736
2020 USP1 interacts with and deubiquitinates ERα (estrogen receptor alpha), inhibiting K48-linked poly-ubiquitination and thereby stabilizing ERα protein in breast cancer cells. DUB siRNA library screen, Co-IP, ubiquitination assay Journal of Cancer Medium 33123289
2020 USP1 maintains USP1 protein stability in part by limiting TSC1 levels to sustain mTOR-mediated basal protein synthesis that maintains USP1's own levels, creating an auto-regulatory loop. Co-IP, siRNA knockdown, protein stability assay EMBO reports Low 32133736
2021 The crystal structure of human USP1-UAF1 with and without ubiquitin, and a cryo-EM structure of USP1-UAF1 bound to monoubiquitinated FANCI-FANCD2, reveal that UAF1 drives conformational changes in FANCI-FANCD2 for deubiquitination; an extensive UAF1-FANCI interface (confirmed by mutagenesis) explains why both UAF1 and FANCI are required despite neither being directly catalytic. X-ray crystallography, cryo-EM, mutagenesis, biochemical deubiquitination assay Nature structural & molecular biology High 33795880
2021 The N-terminus of USP1 contains a FANCD2-specific binding sequence required for deubiquitination of K561 on FANCD2; the N-terminus is not required for PCNA or FANCI deubiquitination, and the N-terminus alone is sufficient to confer FANCD2 specificity on a more promiscuous USP. Reconstituted deubiquitination assay with purified monoubiquitinated substrates, N-terminal deletion/chimera mutants Life science alliance High 30456385
2021 Insert L1 of USP1 limits intrinsic USP1 activity and is required for both UAF1-mediated allosteric activation and substrate-dependent (DNA and PCNA) activity enhancement independently of UAF1; insert L3 also contributes to limiting intrinsic activity. Biochemical activity assays with insert deletion mutants, UAF1 activation assays, DNA/PCNA stimulation assays EMBO reports High 33619839
2021 GRP75 forms a complex with USP1 and SIX1, recruiting USP1 to inhibit K48-linked polyubiquitination of SIX1; GRP75's C-terminus (433-679 aa) peptide-binding domain is required for GRP75-USP1-SIX1 complex formation. Co-IP, domain mapping, ubiquitination assay, xenograft model Oncogene Medium 34079090
2021 USP1 interacts with and deubiquitinates BCAT2 at K229; BCAA increases USP1 protein levels via the GCN2-eIF2α pathway, and USP1-mediated BCAT2 stabilization promotes PDAC development. DUB library screen, Co-IP, in vitro deubiquitination assay, K229 site mapping, GCN2-eIF2α pathway analysis National science review Medium 35663242
2021 USP1 interacts with and deubiquitinates RPS16, removing K48-linked ubiquitin chains to prevent proteasomal degradation; catalytically inactive USP1-C90A mutant cannot stabilize RPS16, confirming USP1 enzymatic activity is required. Mass spectrometry, Co-IP, western blot, C90A mutant, ubiquitination assay, xenograft model Journal of experimental & clinical cancer research Medium 34154657
2021 USP1 deubiquitinates Aurora B to prevent its degradation, mediating glucocorticoid resistance in T-ALL; ALKBH5-mediated m6A demethylation increases USP1 mRNA stability, thereby elevating USP1 and Aurora B levels. Co-IP, deubiquitination assay, siRNA knockdown, rescue experiments, in vivo mouse model Molecular carcinogenesis Medium 34169564
2022 Cryo-EM at 2.5-Å resolution of USP1 with and without ML323 reveals that ML323 binds to a cryptic hydrophobic site within USP1, disrupts part of the hydrophobic core, and causes conformational changes in secondary structure that lead to subtle rearrangements in the active site underlying inhibition. Cryo-EM (2.5 Å resolution), structure-based mechanistic analysis Science advances High 36170365
2022 Cells harboring an autocleavage-defective USP1 mutant experience more replication fork-stalling and premature fork termination; USP1 molecules are removed from active DNA synthesis sites by the DNA-dependent metalloprotease Spartan to prevent 'USP1-trapping' lesions; autocleavage enables USP1 recycling from DNA. Autocleavage-defective mutant, super-resolution microscopy, live-cell single-molecule tracking, replication fork assay Nature communications High 35365626
2022 USP1 inhibition leads to decreased DNA synthesis concomitant with S-phase-specific DNA damage; CRISPR screens identify RAD18 and UBE2K (promoting PCNA mono- and polyubiquitination) as required mediators of USP1 dependency; ectopic expression of WT but not K164R PCNA reverses USP1 inhibitor sensitivity, placing USP1 dependency on aberrant processing of ubiquitinated PCNA. CRISPR-Cas9 genome-wide screens, PCNA ubiquitination assay, ectopic PCNA expression (WT vs K164R mutant), DNA synthesis assay Molecular cancer therapeutics High 36228090
2022 USP1 interacts with and deubiquitinates MAST1, preventing its K48-linked polyubiquitination and extending its half-life; USP1-stabilized MAST1 activates MEK1, driving cisplatin resistance. CRISPR/Cas9-based genome-wide dual screen, Co-IP, domain mapping, in vitro deubiquitination assay, half-life analysis, xenograft model Theranostics Medium 35966591
2022 USP1 interacts with and deubiquitinates TAZ via the Hippo pathway in osteosarcoma; USP1 inhibition by ML323 destabilizes TAZ, reducing nuclear accumulation and expression of Hippo downstream genes, suppressing OS growth and metastasis in vitro and in vivo. Co-IP, ubiquitination assay, in vitro and in vivo tumor models International journal of biological sciences Medium 35637948
2022 USP1 interacts with and deubiquitinates MAX, maintaining its stability; USP1-stabilized MAX promotes MYC target gene transcription, contributing to chemotherapy resistance in DLBCL. Co-IP, ubiquitination assay, shRNA/pimozide inhibition, MYC target gene expression, xenograft and PDX models Leukemia Medium 36352191
2023 USP1 deubiquitinates and stabilizes TAZ (WWTR1) in CD4+ T cells, enhancing RORγt activity and Th17 differentiation while promoting Foxp3 proteasomal degradation to suppress Treg differentiation; ML323 inhibition of USP1 shifts this balance toward Treg differentiation in vitro and in vivo. siRNA screen, Co-IP, ubiquitination assay, Th17/Treg differentiation assays, in vivo inflammatory model Cellular & molecular immunology Medium 36600049
2023 The USP1-UAF1 complex interacts with and stabilizes METTL3 by removing K48-linked ubiquitination after spinal cord injury, and this stabilization promotes reactive astrogliosis through METTL3-mediated m6A methylation of YAP1 mRNA. Co-IP, ubiquitination assay, METTL3 conditional KO, m6A-seq, RNA stability assay, in vivo SCI model The Journal of neuroscience Medium 36653190
2023 USP1 interacts with and deubiquitinates PARP1, removing the ubiquitin chain at K197 to prevent its proteasomal degradation; GCN5 acetyltransferase acetylates USP1 at K130, enhancing the USP1-PARP1 interaction and further increasing PARP1 stabilization. Proteomics, ubiquitylome analysis, Co-IP, GST pull-down, immunofluorescence, deletion mutant mapping, acetyltransferase assay Cell death & disease Medium 37821462
2023 USP1 interacts with PLK1 and deubiquitinates it; USP1-stabilized PLK1 promotes LDHA expression and aerobic glycolysis in T-ALL cells. Co-IP, deubiquitination assay, siRNA knockdown, rescue experiments with LDHA Blood advances Medium 36912760
2023 USP1 interacts with and deubiquitinates C/EBPβ, increasing its protein stability; catalytically inactive USP1 has no effect on C/EBPβ stability; USP1-mediated C/EBPβ stabilization promotes adipogenesis and lipid accumulation. Co-IP, ubiquitination assay, USP1 C90A catalytic mutant, adipogenic differentiation assay, HFD mouse model Cell death & disease Medium 38012162
2023 USP1 interacts with the WW domain of TAZ in HCC and stabilizes it by suppressing K11-linked polyubiquitination; a DUB siRNA screen identified USP1 as a critical regulator of Hippo/TAZ signaling activity. DUB siRNA screen, Co-IP, ubiquitination linkage assay, RNA-seq, xenograft model Cell death & disease Medium 37041150
2023 Human cytomegalovirus UL138 interacts with the UAF1-USP1 complex; this interaction activates STAT1 phosphorylation (pSTAT1), and USP1 inhibition disrupts HCMV latency establishment, increasing viral replication. Co-IP, pSTAT1 assay, USP1 inhibitor (ML323), viral replication assay, ChIP of pSTAT1 on viral genome PLoS pathogens Medium 37289831
2023 USP1 inhibitor ML323 stabilizes NLRP3 and AIM2 by deubiquitination in thyroid follicular cells, and USP1 modulates NLRP3 transcription by facilitating p65 nuclear transport; USP1 knockdown reduces pyroptosis markers in vitro and ameliorates HT in vivo. Co-IP, ubiquitination assay, KD/inhibitor, pyroptosis assay, p65 nuclear translocation assay, in vivo HT mouse model Molecular medicine Medium 39134949
2024 USP1 deubiquitinates PARP1 by removing K63-linked polyubiquitination, controlling PARP1 chromatin trapping and PARylation activity, thereby regulating sensitivity to PARP inhibitors; combined USP1/PARP1 blockade enhances replicative stress and cell death. Co-IP, K63-ubiquitination assay, PARP trapping assay, PARylation assay, cell death assay Science advances Medium 39536107
2024 USP1 promotes PRIMPOL-generated ssDNA gap accumulation and their bidirectional expansion by MRE11 and EXO1 nucleases during replication stress; this activity is linked to USP1's role in PCNA deubiquitination, as PCNA ubiquitination prevents gap accumulation. siRNA depletion, ssDNA gap assay, nuclease inhibitor assays, PCNA ubiquitination assay Nucleic acids research Medium 38180818
2024 USP1 inhibition promotes ssDNA gap accumulation at replication forks via RAD18-dependent PCNA monoubiquitination; knockdown of RAD18 causes USP1 inhibitor resistance and suppresses ssDNA gap formation, establishing this as the mechanism of USP1 inhibitor-induced synthetic lethality in BRCA1-deficient cells. ssDNA gap assay, RAD18 KD rescue, PCNA-Ub assay, USP1 inhibitor + PARP inhibitor combination in xenograft and patient-derived organoids Cancer research High 38885312
2024 Cryo-EM structure of USP1 with KSQ-4279 (RO7623066) shows it binds to the same cryptic hydrophobic tunnel-like site as ML323 but disrupts USP1 protein structure in subtly different ways; both inhibitors cause substantial increases in USP1 thermal stability. Cryo-EM, biochemical inhibition assay, thermal stability assay Journal of medicinal chemistry High 39190802
2024 USP1 deubiquitinates BRD4 in vivo and in vitro, increasing BRD4 stability; P53 indirectly represses USP1 transcription through the P21-RB1 axis, thereby promoting BRD4 degradation in liver cancer. In vivo and in vitro ubiquitination/deubiquitination assay, Co-IP, transcriptional reporter, xenograft model The Journal of biological chemistry Medium 38309505
2024 USP1 suppresses cGAS-STING signaling by removing K27-linked oligo-ubiquitination from SAR1A; SAR1A ubiquitination is required to assemble the STING-COP-II transport complex for STING trafficking from ER to Golgi; USP1 inhibition sustains SAR1A ubiquitination and enhances STING activation and Type I IFN production. Chemical DUB screen, Co-IP, ubiquitination linkage assay (K27), STING trafficking assay, IFN reporter, in vivo radiotherapy model Advanced science Medium 39976106
2024 The UAF1-USP1 complex interacts with cGAS, selectively cleaves K48-linked polyubiquitination on cGAS, and stabilizes cGAS protein expression, thereby enhancing cGAS-dependent type I IFN responses during viral infection. Co-IP, ubiquitination (K48 linkage) assay, UAF1 KO, ML323 inhibitor, in vitro and in vivo antiviral assays Journal of immunology Medium 38054892
2016 Usp1 plays a role in centrosome duplication; ectopic expression of catalytically active but not the C90S inactive mutant induced centrosome amplification, while Usp1 ablation in MEFs delayed centrosome duplication; loss of ID1 suppressed Usp1-induced centrosome amplification, indicating ID1 is downstream. Ectopic expression of WT and C90S mutant Usp1, centrosome number assay, Usp1 KO MEFs, ID1 epistasis Cell cycle (Georgetown, Tex.) Medium 26822809
2018 USP1 deubiquitinates and stabilizes EZH2 in glioma cells; β-catenin/TCF4 activates USP1 transcription, and USP1-stabilized EZH2 is recruited to promoters of CDKN1B, RUNX3, and HOXA5, enhancing H3K27me3 and repressing target gene expression. Co-IP, ubiquitination assay, ChIP (EZH2 and H3K27me3), transcriptional reporter, xenograft model Cancer research Medium 30425057
2011 USP1 is phosphorylated by cyclin-dependent kinases (Cdks) in mitosis, and this phosphorylation may prevent premature APC/C(Cdh1)-mediated degradation of USP1 during normal cell cycle progression. Cell cycle analysis, Cdk phosphorylation assay, APC/C(Cdh1) substrate assay Cell cycle (Georgetown, Tex.) Medium 22101265
2021 The USP1-WDR48 complex stabilizes TAK1 by removing its polyubiquitination in vitro; loss of USP1 or WDR48 reduces phosphorylation of Smad2/3, Erk, Jnk, and p38, impairing TGF-β-mediated EMT in TNBC cells. Co-IP, in vitro ubiquitination/deubiquitination assay, phosphorylation western blot, EMT/migration assay Cell cycle (Georgetown, Tex.) Medium 33461373
2020 USP1 deubiquitinates and stabilizes TBLR1 (transducin β-like 1 X-linked receptor 1) in hepatocellular circulating tumor cells, promoting Wnt signaling and CTC survival. Co-IP, ubiquitination assay, USP1 KO, xenograft/CTC survival assay Frontiers in oncology Low 33102219
2025 USP1 can be harnessed in DUBTAC (deubiquitinase-targeting chimera) technology to stabilize target proteins; USP1-recruiting DUBTACs (e.g., MS5310 for CFTR, MS7131 for UTX) effectively stabilize their targets in a manner dependent on engagement of both USP1 and the target, demonstrating USP1 can be redirected to deubiquitinate non-native substrates. DUBTAC bifunctional molecule, protein stability assay, CFTR and UTX deubiquitination, cancer cell proliferation assay Journal of the American Chemical Society Medium 40252079
2020 USP1 interacts with and deubiquitinates PHLPP1, stabilizing it; USP1 silencing significantly decreases the half-life of PHLPP1, which amplifies Akt1 phosphorylation, establishing a USP1-PHLPP1-Akt signaling axis in lung cancer cells. Co-IP, GST pull-down, CHX half-life assay, siRNA knockdown, phospho-Akt western blot Journal of cancer research and clinical oncology Medium 22426999

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Molecular cell 486 15694335
2014 A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses. Nature chemical biology 226 24531842
2011 USP1 deubiquitinates ID proteins to preserve a mesenchymal stem cell program in osteosarcoma. Cell 223 21925315
2009 Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Developmental cell 210 19217432
2011 Selective and cell-active inhibitors of the USP1/ UAF1 deubiquitinase complex reverse cisplatin resistance in non-small cell lung cancer cells. Chemistry & biology 192 22118673
2018 USP1 Is Required for Replication Fork Protection in BRCA1-Deficient Tumors. Molecular cell 154 30576655
2013 Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Molecular cancer therapeutics 154 24130053
2013 USP1 deubiquitinase: cellular functions, regulatory mechanisms and emerging potential as target in cancer therapy. Molecular cancer 147 23937906
2010 Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear antigen (PCNA) through Its interactions with PCNA and USP1. The Journal of biological chemistry 122 20147293
2019 USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability. Science advances 108 31086816
2011 The USP1/UAF1 complex promotes double-strand break repair through homologous recombination. Molecular and cellular biology 106 21482670
2020 USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation. EMBO reports 101 32133736
2018 USP1 inhibition destabilizes KPNA2 and suppresses breast cancer metastasis. Oncogene 101 30531833
2010 Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1. Stem cells (Dayton, Ohio) 95 20506303
2015 USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance. Neuro-oncology 92 26032834
2017 Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells. Clinical cancer research : an official journal of the American Association for Cancer Research 81 28270494
2017 USP1-UAF1 deubiquitinase complex stabilizes TBK1 and enhances antiviral responses. The Journal of experimental medicine 69 29138248
2012 The auto-generated fragment of the Usp1 deubiquitylase is a physiological substrate of the N-end rule pathway. Molecular cell 61 23159736
2023 Ubiquitinated PCNA Drives USP1 Synthetic Lethality in Cancer. Molecular cancer therapeutics 59 36228090
2011 APC/CCdh1-dependent proteolysis of USP1 regulates the response to UV-mediated DNA damage. The Journal of cell biology 58 21768287
2011 USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation. Human molecular genetics 56 21389083
2014 Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer. Journal of medicinal chemistry 55 25229643
2019 DNA requirement in FANCD2 deubiquitination by USP1-UAF1-RAD51AP1 in the Fanconi anemia DNA damage response. Nature communications 54 31253762
2018 USP1 (ubiquitin specific peptidase 1) targets ULK1 and regulates its cellular compartmentalization and autophagy. Autophagy 54 30335599
2018 Aberrant Activation of β-Catenin Signaling Drives Glioma Tumorigenesis via USP1-Mediated Stabilization of EZH2. Cancer research 53 30425057
2021 Diet high in branched-chain amino acid promotes PDAC development by USP1-mediated BCAT2 stabilization. National science review 50 35663242
2021 USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells. Journal of experimental & clinical cancer research : CR 47 34154657
2021 Structural basis of FANCD2 deubiquitination by USP1-UAF1. Nature structural & molecular biology 45 33795880
2012 A noncanonical cysteine protease USP1 is activated through active site modulation by USP1-associated factor 1. Biochemistry 45 22439892
2022 USP1-trapping lesions as a source of DNA replication stress and genomic instability. Nature communications 44 35365626
2020 USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer. Cancers 43 33114077
2012 USP1 regulates AKT phosphorylation by modulating the stability of PHLPP1 in lung cancer cells. Journal of cancer research and clinical oncology 38 22426999
2022 CRISPR/Cas9-based genome-wide screening for deubiquitinase subfamily identifies USP1 regulating MAST1-driven cisplatin-resistance in cancer cells. Theranostics 37 35966591
2022 Inhibition of USP1 enhances anticancer drugs-induced cancer cell death through downregulation of survivin and miR-216a-5p-mediated upregulation of DR5. Cell death & disease 37 36153316
2022 Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC. Cell death & disease 37 36357365
1998 Identification and chromosomal assignment of USP1, a novel gene encoding a human ubiquitin-specific protease. Genomics 37 9806842
2024 The USP1 Inhibitor KSQ-4279 Overcomes PARP Inhibitor Resistance in Homologous Recombination-Deficient Tumors. Cancer research 36 39402989
2020 Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy. Cancer science 36 32133742
2016 Gene silencing of USP1 by lentivirus effectively inhibits proliferation and invasion of human osteosarcoma cells. International journal of oncology 34 27840911
2009 Inactivation of PadR, the repressor of the phenolic acid stress response, by molecular interaction with Usp1, a universal stress protein from Lactobacillus plantarum, in Escherichia coli. Applied and environmental microbiology 34 19542339
2023 USP1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing TAZ. Cellular & molecular immunology 33 36600049
2021 A new role of GRP75-USP1-SIX1 protein complex in driving prostate cancer progression and castration resistance. Oncogene 33 34079090
2016 Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance. Cell cycle (Georgetown, Tex.) 33 26825230
2023 USP1 modulates hepatocellular carcinoma progression via the Hippo/TAZ axis. Cell death & disease 31 37041150
2018 MicroRNA-192-5p suppresses the initiation and progression of osteosarcoma by targeting USP1. Oncology letters 31 29731868
2016 The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair. Cell cycle (Georgetown, Tex.) 31 27463890
2023 Deubiquitinase USP1 enhances CCAAT/enhancer-binding protein beta (C/EBPβ) stability and accelerates adipogenesis and lipid accumulation. Cell death & disease 30 38012162
2022 Cryo-EM reveals a mechanism of USP1 inhibition through a cryptic binding site. Science advances 30 36170365
2021 ALKBH5-mediated m6A-demethylation of USP1 regulated T-cell acute lymphoblastic leukemia cell glucocorticoid resistance by Aurora B. Molecular carcinogenesis 30 34169564
2020 The deubiquitinating enzyme USP1 modulates ERα and modulates breast cancer progression. Journal of Cancer 30 33123289
2016 PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells. Cancer research 30 26951930
2012 Two nuclear localization signals in USP1 mediate nuclear import of the USP1/UAF1 complex. PloS one 30 22701671
2023 USP1 promotes cholangiocarcinoma progression by deubiquitinating PARP1 to prevent its proteasomal degradation. Cell death & disease 29 37821462
2022 USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ. International journal of biological sciences 29 35637948
2022 Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma. Leukemia 28 36352191
2023 USP1/UAF1-Stabilized METTL3 Promotes Reactive Astrogliosis and Improves Functional Recovery after Spinal Cord Injury through m6A Modification of YAP1 mRNA. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 36653190
2020 USP1 Maintains the Survival of Liver Circulating Tumor Cells by Deubiquitinating and Stabilizing TBLR1. Frontiers in oncology 25 33102219
2013 CAPNS1 regulates USP1 stability and maintenance of genome integrity. Molecular and cellular biology 25 23589330
2011 Insights into phosphorylation-dependent mechanisms regulating USP1 protein stability during the cell cycle. Cell cycle (Georgetown, Tex.) 25 22101265
2024 CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin. Oncogene 24 38366146
2018 Specificity for deubiquitination of monoubiquitinated FANCD2 is driven by the N-terminus of USP1. Life science alliance 24 30456385
2024 USP1-dependent nucleolytic expansion of PRIMPOL-generated nascent DNA strand discontinuities during replication stress. Nucleic acids research 22 38180818
2021 USP1-WDR48 deubiquitinase complex enhances TGF-β induced epithelial-mesenchymal transition of TNBC cells via stabilizing TAK1. Cell cycle (Georgetown, Tex.) 22 33461373
2021 Inhibition of USP1 induces apoptosis via ID1/AKT pathway in B-cell acute lymphoblastic leukemia cells. International journal of medical sciences 21 33390793
2015 Structure-function analysis of USP1: insights into the role of Ser313 phosphorylation site and the effect of cancer-associated mutations on autocleavage. Molecular cancer 21 25744535
2024 Single-Stranded DNA Gap Accumulation Is a Functional Biomarker for USP1 Inhibitor Sensitivity. Cancer research 20 38885312
2023 USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis. Blood advances 19 36912760
2024 Structural and Biochemical Insights into the Mechanism of Action of the Clinical USP1 Inhibitor, KSQ-4279. Journal of medicinal chemistry 17 39190802
2023 Human cytomegalovirus UL138 interaction with USP1 activates STAT1 in infection. PLoS pathogens 17 37289831
2019 Circular RNA USP1 regulates the permeability of blood-tumour barrier via miR-194-5p/FLI1 axis. Journal of cellular and molecular medicine 17 31654502
2024 USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity. Science advances 16 39536107
2023 The role of USP1 deubiquitinase in the pathogenesis and therapy of cancer. Acta biochimica Polonica 16 37331010
2021 Insert L1 is a central hub for allosteric regulation of USP1 activity. EMBO reports 16 33619839
2018 Loss of Deubiquitinase USP1 Blocks Pancreatic β-Cell Apoptosis by Inhibiting DNA Damage Response. iScience 16 30227958
2022 ML323, a USP1 inhibitor triggers cell cycle arrest, apoptosis and autophagy in esophageal squamous cell carcinoma cells. Apoptosis : an international journal on programmed cell death 15 35654870
2019 TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1. iScience 15 31376680
2023 USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma. Molecular cancer research : MCR 14 37478161
2022 USP1 Inhibits NF-κB/NLRP3 Induced Pyroptosis through TRAF6 in Osteoblastic MC3T3-E1 Cells. Journal of musculoskeletal & neuronal interactions 14 36458391
2021 USP1 Promotes GC Metastasis via Stabilizing ID2. Disease markers 14 34873426
2025 USP1 inhibition: A journey from target discovery to clinical translation. Pharmacology & therapeutics 13 40274197
2024 Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors. European journal of medicinal chemistry 12 38889606
1988 Progesterone and antiprogesterone (RU 38486) modulation of estrogen-inducible glycoprotein (USP-1) synthesis and secretion in rat uterine epithelial cells. Endocrinology 12 3345728
2024 Multi-regulatory potency of USP1 on inflammasome components promotes pyroptosis in thyroid follicular cells and contributes to the progression of Hashimoto's thyroiditis. Molecular medicine (Cambridge, Mass.) 11 39134949
2015 Cheminformatics models based on machine learning approaches for design of USP1/UAF1 abrogators as anticancer agents. Systems and synthetic biology 11 25972987
2025 Characterization of TNG348: A Selective, Allosteric USP1 Inhibitor That Synergizes with PARP Inhibitors in Tumors with Homologous Recombination Deficiency. Molecular cancer therapeutics 10 39886906
2022 ML323 suppresses the progression of ovarian cancer via regulating USP1-mediated cell cycle. Frontiers in genetics 10 35923700
2020 The DNA-binding activity of USP1-associated factor 1 is required for efficient RAD51-mediated homologous DNA pairing and homology-directed DNA repair. The Journal of biological chemistry 10 32350107
2020 Inhibition of USP1, a new partner of Bcr-Abl, results in decrease of Bcr-Abl level in K562 cells. Experimental oncology 10 32602291
2019 Interaction of the Human Papillomavirus E1 Helicase with UAF1-USP1 Promotes Unidirectional Theta Replication of Viral Genomes. mBio 10 30890612
2016 The role of USP1 autocleavage in DNA interstrand crosslink repair. FEBS letters 10 26783108
2025 Targeting USP1 Potentiates Radiation-Induced Type I IFN-Dependent Antitumor Immunity by Enhancing Oligo-Ubiquitinated SAR1A-Mediated STING Trafficking and Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 39976106
2024 The UAF1-USP1 Deubiquitinase Complex Stabilizes cGAS and Facilitates Antiviral Responses. Journal of immunology (Baltimore, Md. : 1950) 9 38054892
2016 A novel role for the deubiquitinase USP1 in the control of centrosome duplication. Cell cycle (Georgetown, Tex.) 9 26822809
2025 USP1 in regulation of DNA repair pathways. DNA repair 8 39848025
2023 Inhibition of USP1 ameliorates hypertensive nephropathy through regulating oxidative stress and ferroptosis: A precise treatment via SJB3-019A nanodelivery. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 8 37949326
2022 Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway. The Biochemical journal 8 36240066
2020 USP1 inhibitor ML323 enhances osteogenic potential of human dental pulp stem cells. Biochemical and biophysical research communications 8 32546349
2017 The Role of the Complex USP1/WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells. Current stem cell research & therapy 8 28302046
2025 Harnessing the Deubiquitinase USP1 for Targeted Protein Stabilization. Journal of the American Chemical Society 7 40252079
2024 The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1. The Journal of biological chemistry 7 38309505