| 2005 |
USP1 is a deubiquitinating enzyme that physically associates with FANCD2 and deubiquitinates monoubiquitinated FANCD2; inhibition of USP1 leads to hyperaccumulation of monoubiquitinated FANCD2, and USP1 co-localizes with FANCD2 in chromatin after DNA damage. |
RNAi screen, Co-IP, chromatin fractionation, chromosomal aberration assay |
Molecular cell |
High |
15694335
|
| 2009 |
Targeted deletion of mouse Usp1 results in elevated perinatal lethality, male infertility, crosslinker hypersensitivity, and an FA phenotype; Usp1−/− MEFs show heightened monoubiquitinated Fancd2 in chromatin, impaired Fancd2 foci assembly, and a defect in homologous recombination repair. Double knockout of Usp1 and Fancd2 produces a more severe phenotype than either single knockout, placing Usp1 downstream in the FA pathway. |
Targeted gene knockout (mouse), MEF analysis, epistasis (double KO), chromosomal aberration assay, HR repair assay |
Developmental cell |
High |
19217432
|
| 1998 |
USP1 encodes a 785-amino-acid ubiquitin-specific protease; recombinant USP1 protein displays genuine UBP deubiquitinase activity, correctly cleaving Ub-beta-galactosidase to produce ubiquitin and beta-galactosidase. |
Recombinant protein expression, in vitro enzymatic cleavage assay |
Genomics |
High |
9806842
|
| 2010 |
Human ELG1 interacts with the USP1-UAF1 deubiquitinase complex and specifically directs it toward PCNA deubiquitination (but not FANCD2 deubiquitination); a conserved N-terminal domain of ELG1 is required for USP1-UAF1 interaction and PCNA monoubiquitination downregulation. |
Co-IP, RNAi knockdown, domain mapping |
The Journal of biological chemistry |
Medium |
20147293
|
| 2011 |
USP1 acts in complex with UAF1 to promote homologous recombination (HR)-mediated double-strand break repair; USP1/UAF1-deficient chicken DT40 cells show sensitivity to camptothecin and PARP inhibitors, and disruption of NHEJ in UAF1-deficient cells restores resistance, indicating that USP1/UAF1 promotes HR at least partly by suppressing NHEJ. |
Gene knockout in chicken DT40 cells, drug sensitivity assay, epistasis with NHEJ disruption |
Molecular and cellular biology |
High |
21482670
|
| 2011 |
USP1 deubiquitinates ID1, ID2, and ID3 proteins (inhibitors of DNA binding), thereby stabilizing them and promoting a stem cell-like mesenchymal state in osteosarcoma; USP1 knockdown precipitates ID protein destabilization, cell-cycle arrest, and osteogenic differentiation. |
Co-IP, ubiquitination assay, RNAi knockdown, protein stability assay, mouse knockout phenotype (osteopenia) |
Cell |
High |
21925315
|
| 2011 |
USP1 is degraded in G1 phase via APC/C(Cdh1)-mediated ubiquitination; low USP1 levels in G1 are required to permit PCNA monoubiquitination in response to UV damage; expression of a degradation-resistant USP1 mutant inhibits PCNA monoubiquitination during G1, compromising translesion synthesis polymerase recruitment. |
Cell-cycle synchronization, protein stability assay, APC/C(Cdh1) substrate analysis, PCNA ubiquitination assay |
The Journal of cell biology |
High |
21768287
|
| 2011 |
USP1 depletion stimulates DDB1-dependent degradation of phosphorylated CHK1; USP1 maintains total and phosphorylated CHK1 levels in response to genotoxic stress, both in a FANCD2-monoubiquitination-dependent and -independent manner, placing USP1 in a feedback circuit that downregulates CHK1 after DNA damage. |
RNAi knockdown, protein stability assay, epistasis with monoubiquitinated FANCD2 |
Human molecular genetics |
Medium |
21389083
|
| 2012 |
USP1 undergoes autocleavage at a conserved G670/G671 diglycine motif, producing a C-terminal fragment (Gln-Usp1(Ct)) that is targeted for degradation by the Arg/N-end rule pathway through deamidation of its N-terminal Gln by Ntaq1; metabolic stabilization of Gln-Usp1(Ct) decreases PCNA monoubiquitination and causes hypersensitivity to UV irradiation. |
In vivo autocleavage assay, N-end rule pathway analysis, PCNA ubiquitination assay, UV sensitivity assay |
Molecular cell |
High |
23159736
|
| 2012 |
UAF1 activates USP1 by modulating its active site conformation: UAF1 lowers the pKa of the catalytic histidine in USP1 by ~0.43 pH units (without changing the catalytic cysteine pKa), facilitating general base catalysis at neutral pH. USP1/UAF1 uses a general base catalysis mechanism (not an ion-pair mechanism), with a kinetic isotope effect of ~2.8–3.0 and single proton transfer in the transition state. |
In vitro kinetic analysis (pH-dependent inactivation, solvent kinetic isotope effect, proton inventory), active site mutagenesis |
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 subsequently translocates to the nucleus via USP1 NLSs. The UAF1-binding site was mapped to a conserved ~100 amino acid motif in the Fingers subdomain of USP1 (residues 420–520). |
Nuclear localization signal mutagenesis, cellular relocation assay, deletion mapping |
PloS one |
Medium |
22701671
|
| 2013 |
CAPNS1 (calpain regulatory subunit) is required for USP1 stability; calpain stabilizes USP1 by activating Cdk5, which in turn inhibits Cdh1 and thereby prevents APC/C(Cdh1)-mediated USP1 degradation. Loss of CAPNS1 increases ubiquitinated PCNA, favors polymerase-η loading on chromatin, and increases mutagenesis. |
RNAi knockdown (CAPNS1), protein stability assay, rescue with Cdk5/p25 overexpression, PCNA ubiquitination and pol-η chromatin loading assay |
Molecular and cellular biology |
Medium |
23589330
|
| 2014 |
The USP1-UAF1 complex is a key regulator of the DNA translesion synthesis (TLS) and Fanconi anemia (FA) deubiquitination pathways; ML323, a potent and selective inhibitor of USP1-UAF1, increases monoubiquitinated PCNA and FANCD2 in cells after UV/cisplatin damage, demonstrating that deubiquitination by this complex is required for the DNA damage response. |
Selective small-molecule inhibitor (ML323) with selectivity profiling against panel of DUBs, cell-based PCNA/FANCD2 ubiquitination assay |
Nature chemical biology |
High |
24531842
|
| 2016 |
USP1 binds to and is stimulated by fork DNA; a truncated USP1 lacking its DNA-binding region is not stimulated by DNA and fails to localize to and protect replication forks. Persistence of monoubiquitinated PCNA at stalled replication forks is the mechanism of cell death in BRCA1-deficient cells lacking USP1. |
DNA-binding assay, truncation mutant analysis, replication fork protection assay (DNA fiber), live-cell imaging/localization, USP1 knockdown/inhibition in BRCA1-deficient cells |
Molecular cell |
High |
30576655
|
| 2016 |
The USP1-UAF1 complex interacts with RAD51AP1 through UAF1; depletion of USP1 or UAF1 destabilizes RAD51AP1. The USP1-UAF1-RAD51AP1 interaction promotes a late step of HR repair (RAD51 foci resolution) independently of FANCD2 deubiquitination. |
Proteomics (UAF1 interactome), Co-IP, domain mapping, RNAi knockdown, RAD51 foci analysis, chromosomal aberration assay |
Cell cycle (Georgetown, Tex.) |
Medium |
27463890
|
| 2016 |
PDGF signaling upregulates USP1 transcription through E2F transcription factors, which directly bind the Usp1 promoter; USP1 then stabilizes ID2, which is required for glioma cell survival in a PDGF-driven mouse model. |
Comparative transcriptomics, ChIP (E2F binding to Usp1 promoter), genetic ablation of Id2/Usp1, pharmacological USP1 inhibition, mouse glioma model |
Cancer research |
Medium |
26951930
|
| 2017 |
The USP1-UAF1 complex stabilizes TBK1 by removing its K48-linked polyubiquitination, thereby preventing TBK1 degradation and enhancing TLR3/4 and RIG-I-induced IRF3 activation and IFN-β secretion during antiviral responses. |
Co-IP, ubiquitination assay (K48-linked), RNAi knockdown, IFN-β reporter assay, ML323 inhibitor in vitro/in vivo |
The Journal of experimental medicine |
Medium |
29138248
|
| 2018 |
USP1 deubiquitinates and stabilizes KPNA2; USP1-mediated stabilization of KPNA2 is required for USP1's pro-metastatic function in breast cancer cells in vitro and in vivo. |
Co-IP, ubiquitination assay, RNAi knockdown, rescue experiments, mouse lung metastasis model |
Oncogene |
Medium |
30531833
|
| 2018 |
USP1 deubiquitinates CHK1 to maintain its phosphorylated levels; USP1 also stabilizes Survivin/BIRC5 in glioblastoma stem cells and Survivin is shown to be downstream of USP1 in EWS cells; USP1 depletion reduces ID1 and CHK1 protein stability in glioblastoma. |
RNAi knockdown, protein stability assay, USP1 inhibitor (pimozide), in vivo mouse model |
Neuro-oncology |
Medium |
26032834
|
| 2018 |
Upon platinum treatment, USP1 is phosphorylated by ATM and ATR kinases, binds to Snail, deubiquitinates and stabilizes Snail protein, thereby promoting tumor dissemination and conferring platinum resistance in ovarian cancer. USP1 knockout or inhibition increased platinum sensitivity and decreased metastatic dissemination in a Snail-dependent manner. |
Co-IP, ubiquitination assay, kinase inhibitor epistasis (ATM/ATR), in vivo mouse model, USP1 knockout/inhibition |
Science advances |
Medium |
31086816
|
| 2019 |
Efficient FANCD2 deubiquitination by USP1-UAF1 requires DNA and DNA binding by UAF1; the DNA-binding activity of RAD51AP1 can substitute for that of UAF1 in FANCD2 deubiquitination in a reconstituted biochemical system. Both UAF1 and RAD51AP1 DNA-binding activities are important for FANCD2 deubiquitination in cells. |
Reconstituted biochemical deubiquitination assay with purified components, DNA-binding mutant analysis, cellular assay with UAF1/RAD51AP1 mutants |
Nature communications |
High |
31253762
|
| 2020 |
USP1 removes K63-linked polyubiquitin chains on Akt to restrict PI3K-Akt-FoxO signaling in mouse muscle during prolonged starvation; a USP1 complex containing Dab2, TSC1/TSC2, and PHLPP1 is identified, with Dab2 essential for Akt recruitment to this complex for PI3K-Akt-FoxO inhibition. |
DUB screening, Co-IP, mass spectrometry, RNAi knockdown in mouse muscle, glucose uptake assay, ubiquitin linkage analysis |
EMBO reports |
Medium |
32133736
|
| 2020 |
USP1 regulates AKT phosphorylation by stabilizing PHLPP1 (a phosphatase that dephosphorylates AKT); USP1 interacts with PHLPP1, and USP1 silencing decreases PHLPP1 half-life and increases AKT1 phosphorylation. |
Co-IP, GST pull-down, CHX stability assay, RNAi knockdown |
Journal of cancer research and clinical oncology |
Medium |
22426999
|
| 2021 |
Crystal structures of human USP1-UAF1 with and without ubiquitin, and cryo-EM of USP1-UAF1 bound to monoubiquitinated FANCI-FANCD2, reveal plasticity in USP1, an extensive interface between UAF1 and FANCI required for substrate recognition, and USP1-UAF1-driven conformational changes in the FANCI-FANCD2 substrate during deubiquitination. Mutagenesis confirmed the UAF1-FANCI interface. |
X-ray crystallography, cryo-EM, site-directed mutagenesis, biochemical deubiquitination assay |
Nature structural & molecular biology |
High |
33795880
|
| 2021 |
Insert L1 in USP1 is a central regulatory hub: it limits intrinsic USP1 activity (together with insert L3), and this inhibition is relieved by UAF1 binding; insert L1 also conveys substrate-dependent (DNA and PCNA) increases in USP1 activity independently of UAF1-mediated activation. |
Biochemical activity assays with USP1 insert deletion mutants, UAF1 activation assays, DNA/PCNA stimulation assays |
EMBO reports |
High |
33619839
|
| 2021 |
USP1 deubiquitinates and stabilizes BCAT2 at the K229 site; BCAA increases USP1 protein at the translational level via the GCN2-eIF2α pathway, forming a feedforward axis that promotes pancreatic cancer development. |
DUB library screen, Co-IP, ubiquitination assay (site-specific), in vitro deubiquitination, in vivo orthotopic mouse model |
National science review |
Medium |
35663242
|
| 2021 |
USP1 interacts with and deubiquitinates EZH2, stabilizing it downstream of a β-catenin/TCF4 transcriptional axis (β-catenin/TCF4 → USP1 transcription → EZH2 stabilization → H3K27me3-mediated gene repression) to drive glioma tumorigenesis. |
Co-IP, ubiquitination assay, ChIP, reporter assay, RNAi/knockdown, in vivo tumor model |
Cancer research |
Medium |
30425057
|
| 2021 |
The molecular chaperone GRP75 recruits USP1 to inhibit K48-linked polyubiquitination of SIX1, forming a GRP75-USP1-SIX1 trimeric complex; the C-terminus of GRP75 (433–679 aa peptide-binding domain) is required for complex formation. |
Co-IP, ubiquitination assay, domain mapping (deletion mutants), in vitro and in vivo tumor models |
Oncogene |
Medium |
34079090
|
| 2022 |
USP1 inhibition causes accumulation of mono- and polyubiquitinated PCNA and leads to reduced PCNA protein levels; ectopic expression of WT PCNA (but not ubiquitin-dead K164R PCNA) reverses USP1 inhibitor sensitivity. RAD18 and UBE2K (promoting PCNA mono- and polyubiquitination respectively) are mediators of USP1 dependency in BRCA1/2-mutant tumors. |
Genome-wide CRISPR-Cas9 screen, PCNA ubiquitination assay, rescue with PCNA K164R mutant, cell viability assay |
Molecular cancer therapeutics |
High |
36228090
|
| 2022 |
Cells with an autocleavage-defective USP1 mutant (still able to deubiquitinate PCNA) experience more replication fork-stalling and premature fork termination; super-resolution microscopy and live-cell single-molecule tracking show that USP1 autocleavage is required for its proper recycling from sites of active DNA synthesis ('USP1-trapping'); the metalloprotease Spartan facilitates removal of USP1 molecules from DNA to counteract USP1-trapping cytotoxicity. |
Autocleavage-defective mutant knock-in, super-resolution microscopy, live-cell single-molecule tracking, DNA fiber assay, Spartan epistasis |
Nature communications |
High |
35365626
|
| 2022 |
Cryo-EM at 2.5 Å resolution of the USP1-UAF1-ML323 inhibitor complex reveals that ML323 binds to a cryptic hydrophobic site in USP1, disrupting part of its hydrophobic core and inducing conformational changes in secondary structure that subtly rearrange the active site to achieve inhibition. |
Cryo-EM structure determination, with and without inhibitor |
Science advances |
High |
36170365
|
| 2022 |
USP1 interacts with MAX and maintains MAX protein stability through deubiquitination; this promotes transcription of MYC target genes and contributes to chemotherapy resistance in B-cell lymphoma. |
Co-IP, ubiquitination assay, RNAi/shRNA knockdown, in vivo mouse lymphoma model |
Leukemia |
Medium |
36352191
|
| 2022 |
USP1 identifies MAST1 as a substrate; USP1 interacts with MAST1, prevents its K48-linked polyubiquitination, and extends its half-life, thereby stabilizing MAST1 and promoting MAST1-mediated MEK1 activation and cisplatin resistance. |
CRISPR/Cas9 genome-wide dual screen, Co-IP, in vitro deubiquitination assay, ubiquitination linkage analysis (K48), half-life analysis, xenograft mouse model |
Theranostics |
Medium |
35966591
|
| 2018 |
N-terminus of USP1 contains a FANCD2-specific binding sequence required for deubiquitination of K561 on FANCD2, whereas the N-terminus is not required for PCNA or FANCI deubiquitination; the N-terminus of USP1 is sufficient to engineer substrate specificity into a more promiscuous USP. |
Reconstituted in vitro deubiquitination of purified monoubiquitinated FANCD2/FANCI/PCNA, N-terminal deletion and chimera mutants |
Life science alliance |
High |
30456385
|
| 2015 |
USP1 is phosphorylated by CDKs in mitosis, and this phosphorylation may prevent premature APC/C(Cdh1)-mediated degradation during normal cell cycle progression. The S313 phosphorylation site is not critical for PCNA deubiquitination or UAF1 binding in a cellular environment. The UAF1-binding site in USP1 maps to residues 420–520 (Fingers subdomain). Autocleavage of USP1 can occur in cis and is disrupted by the cancer-associated mutation L669P. |
Structure-function analysis with USP1 mutants (S313A, S313D, GG/AA, cancer-associated mutations), nuclear relocation assay, PCNA deubiquitination assay, Co-IP |
Molecular cancer |
Medium |
25744535
|
| 2011 |
USP1 protein levels are phosphorylated by CDKs during mitosis, and this phosphorylation event may prevent premature degradation by APC/C(Cdh1) during normal cell cycle progression. |
Cell cycle synchronization, phosphorylation assay, CDK inhibitor treatment |
Cell cycle (Georgetown, Tex.) |
Medium |
22101265
|
| 2016 |
USP1 autocleavage (at the GG/AA diglycine motif) is specifically required for USP1 function in ICL repair but not UV repair; an autocleavage-defective mutant Usp1(GG/AA) corrects monoubiquitinated Fancd2 levels and UV resistance in Usp1−/− MEFs, but only partially rescues MMC sensitivity and shows defective Fancd2 foci formation and HR. |
Autocleavage mutant knock-in in Usp1−/− MEFs, MMC/UV sensitivity assay, Fancd2 foci analysis, HR assay |
FEBS letters |
Medium |
26783108
|
| 2019 |
TonEBP regulates PCNA polyubiquitination by sequentially recruiting E3 ligase SHPRH and then deubiquitinase USP1 to DNA damage sites; the Rel-homology domain of TonEBP is essential for interaction with both SHPRH and USP1, PCNA polyubiquitination, and cell survival after DNA damage. |
Co-IP, recruitment assay (chromatin/DNA damage foci), RNAi knockdown, domain deletion mapping |
iScience |
Medium |
31376680
|
| 2020 |
UAF1 deubiquitinates and stabilizes METTL3 by removing K48-linked polyubiquitination after spinal cord injury, and the USP1/UAF1 complex specifically binds METTL3 to maintain its stability. |
Co-IP, ubiquitination assay (K48-linked), conditional knockout, in vivo SCI model |
The Journal of neuroscience |
Medium |
36653190
|
| 2021 |
USP1 identifies ULK1 as a substrate, removing K63-linked ubiquitination from ULK1; USP1 depletion or inhibition causes ULK1 compartmentalization into a detergent-insoluble (urea-soluble) fraction enriched in SQSTM1/p62 and HDAC6, forming protein aggregates, and inhibits canonical autophagic flux while promoting an alternative lysosomal-mediated degradation route. |
Co-IP, ubiquitin linkage analysis (K63), cellular fractionation, immunofluorescence, RNAi knockdown, pimozide inhibition |
Autophagy |
Medium |
30335599
|
| 2016 |
USP1 plays a role in regulating centrosome duplication; ectopic expression of catalytically active (but not C90S inactive) Usp1 induces centrosome amplification, abnormal mitotic spindles, chromosome missegregation, and aneuploidy. Loss of ID1 suppresses Usp1-induced centrosome amplification, placing ID1 downstream of USP1 in this process. |
Usp1 overexpression and C90S catalytic mutant, centrosome counting, mitotic spindle analysis, ID1 knockdown epistasis in Usp1−/− MEFs |
Cell cycle (Georgetown, Tex.) |
Medium |
26822809
|
| 2020 |
USP1 interacts with TAZ/WWTR1 and increases TAZ protein stability by preventing its poly-ubiquitination; loss of USP1 reduces TAZ protein levels and decreases cell proliferation and migration of breast cancer cells. |
siRNA DUB library screen, Co-IP, ubiquitination assay, RNAi knockdown |
Cancers |
Medium |
33114077
|
| 2023 |
USP1 interacts with the WW domain of TAZ and suppresses K11-linked polyubiquitination of TAZ to enhance TAZ stability and Hippo/TAZ signaling in HCC; USP1 depletion leads to decreased TAZ nuclear accumulation and downstream Hippo target gene expression. |
DUB siRNA screen, Co-IP, domain mapping (WW domain), ubiquitin linkage-specific assay (K11), RNAi knockdown, in vivo tumor model |
Cell death & disease |
Medium |
37041150
|
| 2023 |
USP1 interacts with PARP1 and removes the ubiquitin chain at K197 of PARP1 to prevent its proteasomal degradation; GCN5 acetyltransferase acetylates USP1 at K130, enhancing USP1-PARP1 affinity and further increasing PARP1 stabilization. |
Proteomics/ubiquitylome analysis, Co-IP, GST pull-down, immunofluorescence, deletion mutant mapping, in vitro/in vivo tumor models |
Cell death & disease |
Medium |
37821462
|
| 2024 |
USP1 removes K63-linked polyubiquitin chains from PARP1 and controls PARP1 chromatin trapping and PARylation activity, thereby regulating sensitivity to PARP inhibitors. |
Co-IP, ubiquitin linkage analysis (K63), chromatin trapping assay, PARylation assay, RNAi/knockout |
Science advances |
Medium |
39536107
|
| 2024 |
USP1 inhibition promotes accumulation of ssDNA gaps at replication forks in BRCA1-deficient cells via RAD18-dependent PCNA monoubiquitination; RAD18 knockdown causes USP1 inhibitor resistance and suppresses ssDNA gap accumulation, defining RAD18-dependent PCNA ubiquitination as the proximal mediator of USP1 dependency. |
ssDNA gap assay, PCNA ubiquitination assay, RAD18 knockdown rescue, patient-derived organoid assay |
Cancer research |
High |
38885312
|
| 2024 |
USP1 inhibitor KSQ-4279 (RO7623066) binds to the same cryptic hydrophobic site as ML323 in USP1 but disrupts the protein structure in subtly different ways; inhibitor binding drives a substantial increase in USP1 thermal stability, mediated through filling a hydrophobic tunnel-like pocket. |
Cryo-EM structure determination, biochemical assays, thermal stability assay |
Journal of medicinal chemistry |
High |
39190802
|
| 2024 |
USP1 depletion suppresses expansion of PRIMPOL-generated ssDNA gaps by preventing MRE11 and EXO1 nuclease-mediated bidirectional gap expansion; USP1's role in promoting gap accumulation is linked to its deubiquitination of PCNA, as PCNA ubiquitination prevents gap accumulation during replication. |
USP1 depletion, PCNA ubiquitination assay, MRE11/EXO1 epistasis, ssDNA gap assay, DSB assay |
Nucleic acids research |
Medium |
38180818
|
| 2023 |
USP1 interacts with Aurora B and deubiquitinates it, maintaining Aurora B stability and mediating T-ALL glucocorticoid resistance; ALKBH5 enhances USP1 expression by reducing m6A modification on USP1 mRNA. |
Co-IP, ubiquitination assay, in vivo mouse model, ALKBH5 knockdown/overexpression, m6A assay |
Molecular carcinogenesis |
Medium |
34169564
|
| 2023 |
USP1 interacts with PLK1, deubiquitinates it, and increases its stability; PLK1 in turn regulates LDHA expression to promote aerobic glycolysis in T-ALL cells. |
Co-IP, ubiquitination assay, overexpression/knockdown epistasis, metabolic assay (lactate) |
Blood advances |
Medium |
36912760
|
| 2021 |
USP1 deubiquitinates RPS16 at K48-linked ubiquitin chains to stabilize it; USP1-C90A catalytic mutant fails to reduce K48-linked ubiquitinated RPS16, confirming enzymatic activity requirement. USP1 depletion mimics RPS16 deficiency in inhibiting HCC growth and metastasis. |
Mass spectrometry, Co-IP, ubiquitination assay, catalytic mutant (C90A), rescue experiments, xenograft mouse model |
Journal of experimental & clinical cancer research |
Medium |
34154657
|
| 2023 |
USP1 deubiquitinates and stabilizes C/EBPβ; USP1 catalytic mutant fails to affect C/EBPβ stability or ubiquitination, demonstrating enzymatic activity requirement. USP1 directly interacts with C/EBPβ and its upregulation during adipocyte differentiation promotes lipid accumulation. |
Co-IP, ubiquitination assay, catalytic mutant (C90A), overexpression/knockdown, USP1 inhibitor (ML323) in vivo mouse model |
Cell death & disease |
Medium |
38012162
|
| 2024 |
USP1 removes SAR1A K27-linked oligo-ubiquitination, thereby blocking SAR1A-mediated STING-COP-II transport complex assembly and STING trafficking from ER to Golgi; USP1 inhibition sustains SAR1A ubiquitination and enhances cGAS-STING pathway activation and Type I IFN production. |
Chemical screen (DUB inhibitors), Co-IP, ubiquitination linkage analysis (K27), STING trafficking assay, IFN reporter assay, USP1 inhibitor (ML323) |
Advanced science |
Medium |
39976106
|
| 2024 |
UAF1-USP1 deubiquitinase complex interacts with cGAS, selectively cleaves K48-linked polyubiquitination of cGAS, and stabilizes cGAS protein expression in macrophages; this provides positive feedback for cGAS-dependent antiviral type I IFN responses. |
Co-IP, ubiquitin linkage analysis (K48), Uaf1 conditional knockout, ML323 inhibitor, IFN reporter assay in vivo |
Journal of immunology |
Medium |
38054892
|
| 2021 |
USP1 deubiquitinates and stabilizes TBLR1, and this promotes survival of circulating tumor cells in hepatocellular carcinoma by regulating Wnt signaling. |
Co-IP, ubiquitination assay, USP1 knockout, in vitro and in vivo CTC survival assay |
Frontiers in oncology |
Low |
33102219
|
| 2023 |
USP1 interacts with Bcr-Abl oncoprotein in the nucleus of K562 CML cells; inhibition of USP1 activity by ML323 reduces Bcr-Abl protein levels. |
Co-IP, Western blot, confocal microscopy, USP1 inhibitor treatment |
Experimental oncology |
Low |
32602291
|
| 2021 |
USP1-WDR48 (UAF1) complex deubiquitinates TAK1 in vitro, reducing its polyubiquitination and stabilizing it, thereby enhancing TGF-β-mediated EMT and migration in TNBC cells. |
Co-IP, in vitro ubiquitination/deubiquitination assay, RNAi knockdown |
Cell cycle (Georgetown, Tex.) |
Low |
33461373
|
| 2025 |
USP1 can be harnessed as a deubiquitinase-targeting chimera (DUBTAC) anchor; USP1-recruiting DUBTACs stabilize CFTR and the tumor suppressor UTX in a USP1-dependent manner, demonstrating that USP1's deubiquitinating activity can be re-directed to non-natural substrates via bifunctional molecules. |
DUBTAC chemical biology, protein stability assay, knockdown epistasis (USP1 depletion reverses stabilization), cellular assays |
Journal of the American Chemical Society |
Medium |
40252079
|
| 2022 |
USP1 deubiquitinates and stabilizes survivin/BIRC5 in renal cell carcinoma and Ewing sarcoma; USP1 inhibition downregulates survivin by removing ubiquitin, and ML323 also upregulates DR5 by decreasing miR-216a-5p. |
Co-IP, ubiquitination assay, siRNA knockdown, USP1 inhibitor (ML323/pimozide), in vivo mouse xenograft |
Cell death & disease |
Medium |
36153316
|
| 2020 |
USP1 interacts with ERα and promotes ERα stability by inhibiting ERα K48-linked poly-ubiquitination in breast cancer cells. |
DUB siRNA library screen, Co-IP, ubiquitination assay (K48-linked), RNAi knockdown |
Journal of Cancer |
Low |
33123289
|
| 2023 |
USP1 stabilizes NLRP3 and AIM2 inflammasome components through deubiquitination, promoting pyroptosis in thyroid follicular cells; USP1 also facilitates p65 nuclear translocation to modulate NLRP3 transcription. |
Co-IP, ubiquitination assay, USP1 knockdown/inhibition, caspase-1/GSDMD-N assay, mouse HT model, AIM2 rescue epistasis |
Molecular medicine |
Low |
39134949
|
| 2025 |
USP1 deubiquitinates and stabilizes KIF11 at the K77 site; high interstitial fluid pressure stabilizes KIF11 in HCC through USP1-mediated deubiquitination. USP1 inhibition by ML323 reduces KIF11 protein levels and suppresses tumor progression in mice. |
Co-IP, proteomic analysis, ubiquitination assay (site-specific K77), in vivo orthotopic mouse model, USP1 inhibitor |
Journal of translational medicine |
Low |
39810156
|