USP1 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 1
HGNC Gene Symbol
USP1
Identifiers
hgnc:12607 NCBIGene:7398 uniprot:O94782
Orthologs
mgi:2385198 rgd:1306461
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP1
Number of Papers
244 retrieved on 2023-02-19

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type
WDR48 WD repeat domain 48 0.547 BioGRID IntAct Pathway Commons INDRA (26) Reactome (4) 0.26 1.34 1.51e-05
TP53 tumor protein p53 -0.275 INDRA (1) Reactome (1) 0.12 0.58 6.44e-02
FANCM FA complementation group M 0.272 Reactome (2)
MDM4 MDM4 regulator of p53 0.261
LIG4 DNA ligase 4 0.26 Reactome (1) 0.01 -0.01 8.60e-01
APEX2 apurinic/apyrimidinic endodeoxyribonuclease 2 0.25 0.31 1.63 1.96e-05
WDR89 WD repeat domain 89 0.249 0.14 0.66 3.75e-02

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP1using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value
GO:0006310 DNA recombination Biological Process 6.80e-07 2.48e-04 7.30e-05
GO:1902525 regulation of protein monoubiquitination Biological Process 1.25e-06 4.55e-04 7.30e-05
GO:0140097 catalytic activity, acting on DNA Molecular Function 1.67e-05 6.09e-03 6.51e-04
GO:0006284 base-excision repair Biological Process 7.13e-05 2.60e-02 1.75e-03
GO:0070646 protein modification by small protein removal Biological Process 7.48e-05 2.72e-02 1.75e-03
GO:0036297 interstrand cross-link repair Biological Process 1.14e-04 4.15e-02 2.05e-03
GO:0010332 response to gamma radiation Biological Process 1.23e-04 4.47e-02 2.05e-03

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP1 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi minerva creeds ubibrowser acsn | geneways tees gnbr semrep isi trips rlimsp medscan eidos sparser reach
USP1 deubiquitinates FANCD2. 10 / 44
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USP1 combined with USP1-associated factor 1 (UAF1) deubiquitinates PCNA or FANCD2 during DNA repair process such as interstrand cross-link (ICL) repair, homologous recombination (HR) repair, and translesion DNA synthesis (TLS) [87].
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USP1 deubiquitylates FancD2-Ub, and USP3 is thought to act on uH2A.
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USP1 deubiquitinates both ub-FANCD2 [XREF_BIBR] and ub-FANCI [XREF_BIBR], thus reverting the critical event in the activation of the FA pathway.
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Upon DNA damage, USP1 is downregulated by transcriptional shut-off [86], perhaps to facilitate FANCD2 mono-ubiquitination.
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Surprisingly, depletion of UBE2M did not reduce the FANCD2 monoubiquitination that is up-regulated by USP1 depletion (XREF_SUPPLEMENTARY), suggesting that the Nedd8 inhibition specifically abrogates FANCD2 monoubiquitination that is induced by exogenous DNA damage.
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How USP1 eventually deubiquitinates the FANCD2 and FANCI complex following the completion of the DNA repair is still a question.
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Monoubiquitinated FANCD2 interacts with the downstream repair proteins BRCA2/FANCD1 and possibly FANCJ and FANCN to repair the DNA crosslinks and other lesions by homologous recombination.In addition to the monoubiquitination of FANCD2, deubiquitination of FANCD2 by deubiquitination enzyme USP1 is known to be required for ICL repair.
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We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2.
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The exact role of deubiquitination of PCNA and FANCD2 by USP1 and UAF1 in human DNA damage response remains to be elucidated.
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Interestingly, the recently identified deubiquitinating enzyme, USP1, negatively regulates both FANCD2 and PCNA monoubiquitination, suggesting an interaction between these seemingly parallel DNA damag[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 deubiquitinates PCNA. 10 / 42
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The mono-ubiquitination of PCNA is usually reversed by USP1, however, USP1 does not cleave UbL73P chains (XREF_FIG).
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Recently, PCNA deubiquitylation by the USP1 and UAF1 complex in conjunction with ELG1, which directs the USP1-UAF1 to ubiquitin-PCNA, has emerged as an important regulatory mechanism of damage bypass.
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Review
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Later studies showed that USP1 also deubiquitinates proliferating cell nuclear antigen (PCNA) and Fanconi anemia complementation group I (FANCI).
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For example, USP1 deubiquitylates mono-ubiquitylated PCNA, which inhibits recruitment of DNA polymerases in the absence of DNA damage, and thereby leads to regulated DNA repair.
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USP1 deubiquitinates PCNA, thus contributing to prevent unscheduled recruitment of error-prone TLS DNA polymerases [XREF_BIBR].
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Interestingly, the recently identified deubiquitinating enzyme, USP1, negatively regulates both FANCD2 and PCNA monoubiquitination, suggesting an interaction between these seemingly parallel DNA damag[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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The USP1 and UAF1 complex also deubiquitinates PCNA-Ub, and deubiquitination requires the PCNA binding protein hELG1.
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Significantly, we report that PCNA polyubiquitination is negatively regulated by USP1.
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USP1 deubiquitinates PCNA and FANCD2 in cells.
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USP1 deubiquitinates FANCI. 10 / 18
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Monoubiquitination or ATR dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was.
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Usp1 deubiquitinates FANCD2 and FANCI in the Falconi anemia pathway, promoting DNA repair.
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We have previously shown that USP1, in complex with its stimulatory binding partner, UAF1, deubiquitinates the Fanconi Anemia (FA) proteins, FANCD2 and FANCI.
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Deubiquitination of FANCD2 and FANCI proteins by the multisubunit protein complex USP1 and UAF1 is required for the completion of the FA pathway.
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Deubiquitination of FANCD2 and FANCI by USP1 in complex with UAF1 is also important for FA pathway function.
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Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was.
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However, in addition to this opposition to activate and monoubiquitinate FANCD2/I, USP1 deubiquitination of FANCI has also been associated with promoting core complex recruitment to the site of DNA da[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Deficiency of USP1 or FANCD2 promotes haematopoietic stem cells defects [50] , and siRNA knockdown experiments have shown that USP1 also deubiquitinates FANCI [48] , but whether this step is indispensable for ICL repair needs to be ascertained.The sliding clamp of DNA replication, also known as the proliferative cell nuclear antigen (PCNA), plays a leading role in the regulation of replicative lesion bypass (reviewed in [51] ).
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The activated FA pathway must be inactivated for completion and recycling of the functional pathway, and this event is regulated by the USP1 and UAF1 deubiquitinating enzyme complex, which deubiquitinates FANCD2 and FANCI.
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How USP1 eventually deubiquitinates the FANCD2 and FANCI complex following the completion of the DNA repair is still a question.
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USP1 deubiquitinates ID1. 10 / 12
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Once the lesion has been repaired, the ID complex is deubiquitinated by the USP1 and UAF1 complex, which also acts on monoubiquitinated PCNA when associated to the RFC subunit ELG1.
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Williams et al. also recently reported that USP1 and UAF1 deubiquitinates and prevents proteasomal degradation of ID (inhibitor of DNA binding) proteins, 13 which have been shown to activate multiple pathways involved in tumor progression, including preservation of the cancer stem cell phenotype.
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Review
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USP1 also deubiquitinates and stabilizes the transcriptional regulators ID1, ID2 and ID3 [XREF_BIBR - XREF_BIBR].
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The FA ID complex is deubiquitinated by the UAF1 and USP1 complex.
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Therefore, we sought a deubiquitinating enzyme that counters ID ubiquitination.We show that USP1 deubiquitinates and stabilizes ID1, ID2, and ID3, resulting in their increased abundance.
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One of the responsible mechanisms for OS pathogenesis is the deubiquitination of ID proteins by enzyme USP1, which helps maintain the OS cell stemness.
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By deubiquitinating ID proteins, USP1 contributes to prevent bHLH mediated differentiation, and thus maintain stem-cell characteristics in osteosarcoma cells [XREF_BIBR].
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To identify a biological context in which USP1 deubiquitinates ID proteins, we examined USP1 expression patterns.
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Another piece of evidence for a tight coordination between the two pathways is the notion that the isopeptidase USP1 mediates deubiquitylation of both PCNA and the ID complex.
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USP1 deubiquitinates ID2. 5 / 5
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Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC.
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To address whether USP1 deubiquitinated ID2 directly, ubiquitinated ID2 purified from 293T cells was incubated in vitro with either wild-type USP1 or USP1 C90S purified separately from 293T cells.
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Therefore, we sought a deubiquitinating enzyme that counters ID ubiquitination.We show that USP1 deubiquitinates and stabilizes ID1, ID2, and ID3, resulting in their increased abundance.
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USP1 also deubiquitinates and stabilizes the transcriptional regulators ID1, ID2 and ID3 [XREF_BIBR - XREF_BIBR].
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USP1 deubiquitinates ubiquitinated PCNA. 4 / 4
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In vitro, the USP1 and UAF1 complex can de-ubiquitinate mono-ubiquitinated PCNA more efficiently than USP1 alone [59].
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USP1 (ubiquitin specific peptidase 1), which promotes de-ubiquitination of mono-ubiquitinated PCNA [57], forms a stable complex with UAF1 (USP1 associated factor 1), which stabilizes and activates USP[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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They observed an increased mutation frequency in cells in which USP1 was inactivated, a result expected if steady-state levels of monoubiquitinated PCNA are upregulated because of reduced deubiquitina[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Following DNA synthesis on damaged DNA templates by TLS polymerase (Mailand et al., 2013), the ubiquitinated PCNA is deubiquitinated by USP1, causing the release of TLS polymerases and re-association [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 deubiquitinates KDM4A. 3 / 3
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3.4 USP1 deubiquitinates KDM4A.
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9, 27, 28 As KDM4A plays a key role in human cancer development, it is possible that in human cancers USP1 promotes the deubiquitination and stabilization of KDM4A.
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A significant decrease in polyubiquitylated KDM4A protein was observed in cells transfected with GST fusion USP1, whereas GST fusion USP1 (CS) was not able to reduce KDM4A ubiquitination.
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USP1 deubiquitinates AKT. 3 / 3
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USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation.
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USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation.
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USP1, similarly to USP12 and USP46, deubiquitinates AKT phosphatases PHLPP and PHLPPL [XREF_BIBR] and relies on UAF1 for its enzymatic activity, while it does not bind to WDR20 or any other additional proteins [XREF_BIBR].
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USP1 deubiquitinates ID3. 3 / 3
1 | 2
ubibrowser
Review
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Therefore, we sought a deubiquitinating enzyme that counters ID ubiquitination.We show that USP1 deubiquitinates and stabilizes ID1, ID2, and ID3, resulting in their increased abundance.
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USP1 also deubiquitinates and stabilizes the transcriptional regulators ID1, ID2 and ID3 [XREF_BIBR - XREF_BIBR].
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USP1 deubiquitinates PHLPP1. 2 / 2
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USP1 [137] and USP46 [138] are other DUBs known to deubiquitinate PHLPP1, with a similar outcome in other cancers as well.
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USP1, similarly to USP12 and USP46, deubiquitinates AKT phosphatases PHLPP and PHLPPL [XREF_BIBR] and relies on UAF1 for its enzymatic activity, while it does not bind to WDR20 or any other additional proteins [XREF_BIBR].
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USP1 deubiquitinates ubiquitinated FANCD2. 2 / 2
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Furthermore, the USP1 and UAF1 complex can readily, and rapidly, de-ubiquitinate mono-ubiquitinated FANCD2 in an in vitro de-ubiquitination reaction [XREF_BIBR].
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Furthermore, the USP1 and UAF1 complex can readily, and rapidly, de-ubiquitinate mono-ubiquitinated FANCD2 in an in vitro de-ubiquitination reaction [165].
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USP1 deubiquitinates ubiquitinated ID2. 1 / 1
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To address whether USP1 deubiquitinated ID2 directly, ubiquitinated ID2 purified from 293T cells was incubated in vitro with either wild-type USP1 or USP1 C90S purified separately from 293T cells.
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USP1 deubiquitinates EZH2. 1 / 1
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beta-catenin and TCF4 activated transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly.
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Modified USP1 leads to the deubiquitination of ID2. 1 / 1
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Both basal and USP1 induced ID2 deubiquitination was enhanced by coexpression of USP1 cofactor WDR48 (Cohn et al., 2007).
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Unubiquitinated USP1 leads to the deubiquitination of PCNA. 1 / 1
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These include the deubiquitylation of PCNA and FANCD2 catalysed by USP1, deubiquitylation and stabilisation of 53BP1 or claspin by USP28 and more recently is has been reported that USP3 catalyses the deubiquitylation of H2AX and gamma-H2AX.
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Modified USP1 leads to the deubiquitination of USP1. 1 / 1
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To further validate this point, experimental evidence has suggested that higher than normal levels of USP1 will inhibit the DNA damage induced monoubiquitination of USP1 targets, such as FANCD2, FANCI, and PCNA, whereas the loss of USP1 has been shown to cause chromosomal instability and elevated perinatal lethality in mice.
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Modified mutated USP1 leads to the deubiquitination of PCNA. 1 / 1
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Importantly, expression of a USP1 mutant that can not be degraded via APC/C (Cdh1) inhibited PCNA monoubiquitination during G1, likely compromising the recruitment of trans-lesion synthesis polymerase to UV repair sites.
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Unubiquitinated USP1 leads to the deubiquitination of FANCD2. 1 / 1
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These include the deubiquitylation of PCNA and FANCD2 catalysed by USP1, deubiquitylation and stabilisation of 53BP1 or claspin by USP28 and more recently is has been reported that USP3 catalyses the deubiquitylation of H2AX and gamma-H2AX.
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USP1 leads to the deubiquitination of TBK1. 1 / 1
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USP1 greatly inhibited TBK1 ubiquitination, whereas USP12 and USP46 had no effects on TBK1 ubiquitination.
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USP1 leads to the deubiquitination of CCP110. 1 / 1
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In addition, over-expression of two unrelated DUBs, USP1 and USP37, did not promote CP110 de-ubiquitylation (XREF_FIG and data not shown).
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USP1 deubiquitinates PHLPP2. 1 / 1
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USP1, similarly to USP12 and USP46, deubiquitinates AKT phosphatases PHLPP and PHLPPL [XREF_BIBR] and relies on UAF1 for its enzymatic activity, while it does not bind to WDR20 or any other additional proteins [XREF_BIBR].
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USP1 deubiquitinates IDS. 1 / 1
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Deubiquitination of IDs by USP1 promotes ID protein stability and prevents stem cell differentiation.
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Modified USP1 leads to the deubiquitination of PCNA. 1 / 1
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Conversely, overexpression of USP1 when cells are treated with hydroxyurea inhibits monoubiquitination of PCNA.
16630883

Other Statements

psp cbn pc bel_lc signor biogrid tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi minerva creeds ubibrowser acsn | geneways tees gnbr semrep isi trips rlimsp medscan eidos sparser reach
WDR48 affects USP1
| 12 39
WDR48 activates USP1.
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WDR48 activates USP1. 10 / 54
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UAF1 stimulates not only USP1, but also two other DUB enzymes, USP12 and USP46.
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WDR48 stimulates the activity of three DUBs, USP12, USP46 and USP1, a DUB which regulates the Fanconi anemia DNA damage pathway (Cohn et al., 2007, 2009; Faesen et al., 2011).
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For example, USP1, USP12, and USP46 are activated by the WD40-repeat containing UAF1, and USP7 is activated by GMPS (Cohn et al., 2007, 2009; Faesen et al., 2011; van der Knaap et al., 2005).
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WDR48 and UAF1 is an activator of USP1 and more recently has been shown to activate USP12 and USP46.
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UAF1 increases the basicity of the USP1 catalytic histidine, increasing its potency as a general base.
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The activation of USP1 by UAF1 takes place through an allosteric mechanism where the catalytic turnover (k cat ) of the enzyme is increased several fold (Cohn et al , xref ).
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Mutation of Ser313 to Ala on USP1 abolished the complex formation between USP1 and UAF1, thus prevented the activation of USP1 by UAF1.
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Although ATAD5 depletion does not alter protein levels of USP1 [XREF_BIBR], since UAF1 increases USP1 activity [XREF_BIBR], it is still possible that ATAD5 regulates deubiquitination activity of USP1 through UAF1.
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Our results support a regulatory mechanism in which UAF1 activates USP1 by modulating its active site conformation.
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For example, in contrast to the USP46 BL1 residue F258, which supports the tail of Ub, the corresponding USP12 residue F262 is pushed into the catalytic cleft and would collide with the substrate.Usin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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WDR48 bound to USP1 activates USP1. 1 / 1
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The formation of USP1 and UAF1 complex greatly stimulates the DUB activity of USP1.
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WDR48 inhibits USP1.
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WDR48 inhibits USP1. 1 / 1
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In vitro, USP1 activity is greatly stimulated by USP1-associated factor 1 (UAF1; also known as WDR48), enhancing USP1 catalytic turnover (k cat ) but not affinity (K m ) for monoubiquitylated substrates 74 .
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WDR48 deubiquitinates USP1.
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WDR48 deubiquitinates USP1. 1 / 1
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The E1 protein from anogenital HPV types interacts with the UAF1 associated deubiquitinating enzymes USP1, USP12, and USP46 to stimulate replication of the viral genome.
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USP1 affects ID1
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USP1 activates ID1.
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USP1 activates ID1. 10 / 16
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These data suggest that ATAD5 regulates interactions between UAF1 and ID1 and this regulatory mechanism for ID1 is different from USP1 mediated ID1 regulation.
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USP1 enhanced protein stability of the ID1 and CHEK1, important regulators of DNA damage response and stem cell maintenance (Lee et al., 2016).
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Collectively, these results indicate that the novel small molecule inhibitors of USP1 promote ID1 degradation and are cytotoxic to leukemic cells.
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In contrast to USP1 knockdown, USP1 overexpression in primary human mesenchymal stem cells (hMSCs) caused ID protein accumulation and interfered with normal differentiation.
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The small molecule inhibitor of USP1 promotes ID1 degradation and has cytotoxicity to leukemic cells [XREF_BIBR].
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More importantly , inhibition of USP1 leads to the downregulated expression of ID1 , further causing the inactivation of PI3K / AKT pathway .
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Besides DNA repair proteins, USP1 also promotes stabilization of ID (ID1-ID4) proteins 31.
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Here, we demonstrate that targeting USP1 with a small molecule, can promote ID1 degradation and cell death in multiple leukemic cell lines.
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Another USP1 selective inhibitor (C527) promotes the degradation of ID1 and induces cytotoxicity in leukemic cells [XREF_BIBR].
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A doxycycline induced USP1 shRNA suppressed USP1 expression and reduced ID1 and ID2 in the xenografts.
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USP1 inhibits ID1.
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USP1 inhibits ID1. 6 / 6
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Moreover, depletion of USP1 by siRNA promoted ID1 degradation in K562 cells (XREF_SUPPLEMENTARY).
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A doxycycline induced USP1 shRNA suppressed USP1 expression and reduced ID1 and ID2 in the xenografts.
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USP1 knockdown in osteosarcoma cells caused ID protein destabilization, p53 independent induction of CDKN1A encoding cyclin dependent kinase inhibitor (CDKI) p21, and cell-cycle arrest.
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Small molecule inhibitors of USP1 target ID1 degradation in leukemic cells.
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small-molecule inhibitors of USP1 promote the degradation of inhibitor of DNA binding 1 (ID1), and are cytotoxic to leukemic cells [XREF_BIBR].
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shRNA resistant wild-type USP1, but not USP1 C90S, suppressed E box driven reporter activity caused by USP1 knockdown, confirming that USP1 catalytic activity is required for bHLH dependent transcript[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1-C90S inhibits ID1. 1 / 1
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shRNA resistant wild-type USP1, but not USP1 C90S, suppressed E box driven reporter activity caused by USP1 knockdown, confirming that USP1 catalytic activity is required for bHLH dependent transcript[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 increases the amount of ID1.
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USP1 increases the amount of ID1. 1 / 1
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Finally, we found that inhibition of USP1 downregulated the expression of ID1 and p-AKT, and upregulated ID1 expression could reverse the suppressive effects of USP1 inhibitor in B-ALL cells.
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USP1 affects cell differentiation
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USP1 inhibits cell differentiation.
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Thus, USP1 overexpression perturbs normal osteoblast differentiation, which is characterized by p53 independent upregulation of multiple CDKIs (Funato et al., 2001; Kenner et al., 2004; Matsumoto et a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Considering the action of the proteins ID, USP1 contributes to prevent differentiation mediated by bHLH and, consequently, keep CSC original characteristics.
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ID2 or USP1 overexpression in mesenchymal stem cells inhibited osteogenic differentiation and promoted retention of mesenchymal stem cell features.
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Finally, USP1 knockdown in osteosarcoma cells causes cell‐cycle arrest and osteogenic differentiation.
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These data, together with a study showing that misregulated ID expression inhibits osteogenic differentiation (Peng et al., 2004), prompted us to investigate whether USP1 overexpression disrupts hMSC [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Conversely, ectopic USP1 expression in mesenchymal stem cells stabilized ID proteins, inhibited osteoblastic differentiation, and enhanced proliferation.
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Importantly, USP1 knockdown results in decreased mesenchymal cell proliferation, and enhanced differentiation of osteosarcoma cells which overexpress USP1 and ID1, providing a rationale for differentiation therapy of many cancer types including leukemia (e.g. acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML)).
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Collectively, our observations suggest that overexpression of USP1 or ID2 is sufficient to block osteoblastic differentiation, promote retention of stem like features, and render cells resistant to di[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 overexpression not only was necessary for the proliferation of several osteosarcoma cell lines, it also was sufficient to prevent normal mesenchymal cell differentiation, capturing the cells in a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Finally, USP1 inhibits cell differentiation by stabilizing tumor promoting inhibitor of DNA binding (ID) proteins XREF_BIBR, XREF_BIBR.
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USP1 activates cell differentiation.
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Recently, the deubiquitinase USP1 was shown to stabilize Id2 and modulate cellular differentiation in osteosarcomas.
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In light of the role that IDs play in stem cell maintenance and regulation of differentiation, we investigated whether either USP1 or ID knockdown in osteosarcoma would trigger osteoblastic differenti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Considering the action of the proteins ID, USP1 contributes to prevent differentiation mediated by bHLH and, consequently, keep CSC original characteristics.
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Suppression of IDs 1-3 blocked colony formation in soft agar, indicating that the IDs are essential for USP1 transformation of NIH 3T3 cells.Because USP1 overexpression impaired osteoblastic different[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 affects FANCD2
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USP1 activates FANCD2.
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USP1 activates FANCD2. 7 / 8
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The uncoupling of monoubiquitination and chromatin enrichment from nuclear foci formation and effective ICL repair has previously been observed : Usp1 -/- murine embryonic fibroblasts display elevated levels of monoubiquitinated Fancd2 and Fancd2 chromatin localization, but fail to support Fancd2 nuclear foci formation and exhibit ICL-hypersensitivity XREF_BIBR.
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This observation indicates that UAF1 activates the DUB enzyme activity of USP1 and that it functions as a scaffolding protein for USP1 targeting FANCD2 [XREF_BIBR, XREF_BIBR].
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USP1 targets FANCD2, FANC1, and PCNA for deubiquitylation.
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USP1 depletion, which also causes an increase in FANCD2-Ub, even in the absence of DNA damage, increased promoter binding of FANCD2-Ub (XREF_FIG).
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Because USP1 is reported to target PCNA and FANCD2 during DNA repair (Nijman et al., 2005; Huang et al., 2006), we also checked if USP1 knockdown produced DNA damage.
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In USP1 depleted cells this fraction is also enriched in SQSTM1 (sequestosome 1), the aggresome marker HDAC6 (histone deacetylase 6), and the prototype of USP1 targets FANCD2 (FA complementation group D2).
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In addition, DUBs involved in DNA damage signaling are USP1 that targets PCNA (proliferating cell nuclear antigen) [76], FANCD2 and FANCI (the Fanconi anemia proteins) [93,94], and USP3 and USP16 that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 inhibits FANCD2.
| 3
USP1 inhibits FANCD2. 3 / 5
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Depletion of Usp1 decreases epidermal proliferation in Fancd2 (+/-) mice.
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However, in FA pathway, disruption of USP1 gene causes accumulation of the monoubiquitinated forms of FANCD2 and FANCI but increases ICL hypersensitivity and genomic instability [XREF_BIBR, XREF_BIBR].
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However, in FA pathway, disruption of USP1 gene causes accumulation of the monoubiquitinated forms of FANCD2/FANCI but increases ICL hypersensitivity and genomic instability [49, 77] .
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USP1 decreases the amount of FANCD2.
| 4
USP1 decreases the amount of FANCD2. 2 / 2
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Small molecule inhibitors of Usp1 may enhance FANCD2-Ub levels and TAp63 levels and perhaps promote cellular senescence.
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We found that USP1 inhibition by SJB increased the levels of both Ub-FANCD2 and Ub-FANCI in MM cells.
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USP1 bound to WDR48 decreases the amount of FANCD2. 1 / 1
| 1
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Disruption of USP1/UAF1 complex promote level of FANCD2/FANCI ubiquitination and DNA repair defects, suggesting a failure in the completion of FA pathway (Nijman et al., 2005b, Smogorzewska et al., 2007).
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Modified USP1 decreases the amount of FANCD2. 1 / 1
| 1
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These data further indicate that a decrease in Usp1 expression causes an increase in Fancd2-Ub levels, and that this increase may account for the decreased epidermal cell proliferation in the double heterozygote animals.
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USP1 increases the amount of FANCD2.
| 1
USP1 increases the amount of FANCD2. 1 / 1
| 1
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In wild-type MEFs, Usp1 depletion increased the levels of Fancd2-Ub, TAp63, and p21 (XREF_FIG, lanes 1, 2) and enhanced OIS (XREF_FIG).
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Gene silencing of USP1 by lentivirus effectively inhibits proliferation and invasion of human osteosarcoma cells.
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Notably , downregulation of USP1 could inhibit cell proliferation and promote apoptosis in a variety of solid tumors 9,11,12 .
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Consistent with increased p21, USP1 knockdown reduced U2-OS cell proliferation.
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Similarly , pharmacological inhibition of USP1 by SJB3-019A significantly repressed cell proliferation and triggered B-ALL cell apoptosis .
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Conversely, ectopic USP1 expression in mesenchymal stem cells stabilized ID proteins, inhibited osteoblastic differentiation, and enhanced proliferation.
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Recent studies have demonstrated that USP1 inhibition induced apoptosis and suppressed cell proliferation in acute myeloid leukemia ( AML ) and MM cells 12 , 13 .
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USP1 knockdown similarly reduced proliferation in HOS, SAOS, and SJSA, but not MG-63 osteosarcoma cells.
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Similarly, pharmacological inhibition of USP1 by SJB3-019A significantly repressed cell proliferation and triggered B-ALL cell apoptosis.
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In addition, inhibition of USP1 decreased PC proliferation and promoted response to therapeutic agent enzalutamide in a KDM4A dependent manner.
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USP1 knockdown inhibited cell proliferation by more than 2-fold within 72h of seeding and showed a simultaneous increase in caspase activity.
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shRNA resistant wild-type USP1, but neither USP1 C90S nor USP1Delta260-300, restored cell proliferation, indicating that both USP1 catalytic activity and ID substrate recognition are required to maint[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 inhibits cell population proliferation. 3 / 3
| 3
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USP1 downregulation decreased expressions of fibrosis related genes, suppressed proliferation, and promoted apoptosis in TGF-beta1-induced LX-2 cells, which were reversed by SNAIL overexpression.
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Depletion of Usp1 decreases epidermal proliferation in Fancd2 (+/-) mice.
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Collectively, our results suggest that silencing USP1 inhibits cell proliferation and invasion in U2OS cells.
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USP1 affects PCNA
| 15
USP1 activates PCNA.
| 8
USP1 activates PCNA. 6 / 7
| 6
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USP1 also targets PCNA during replication stress.
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Whereas UAF1 displays no detectable activity, and isolated Usp1 shows only low levels of activity toward PCNA-Ub, stoichiometric mixtures of Usp1 and UAF1 are highly active, confirming that the PCNA-Ub can be targeted by Usp1 and UAF1 (XREF_FIG).
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In addition, DUBs involved in DNA damage signaling are USP1 that targets PCNA (proliferating cell nuclear antigen) [76], FANCD2 and FANCI (the Fanconi anemia proteins) [93,94], and USP3 and USP16 that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Because USP1 is reported to target PCNA and FANCD2 during DNA repair (Nijman et al., 2005; Huang et al., 2006), we also checked if USP1 knockdown produced DNA damage.
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It has been reported that USP1 depletion from Rad18 deficient cells induces PCNA monoubiqutinatiton, indicating that other E3 ubiquitin ligase (s) carry out this function independent of Rad18.
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Similar results have been seen in the case of Usp1 and Uaf -1 where knockdown of either protein alone altered the ubiquitination status of Usp1 targets PCNA and FANCD2, in this example an epistatic relationship between Usp1 and Uaf-1 was observed [XREF_BIBR].
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USP1 activates ubiquitinated PCNA. 1 / 1
| 1
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Oxidative stress not only induces DNA damages, but also inactivates USP1, allowing ubiquitinated PCNA to rapidly accumulate in cells to launch the TLS programme.
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USP1 bound to WDR48 activates PCNA. 1 / 1
| 1
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The USP1 and UAF1 complex promotes homologous recombination and DNA cross-link repair via deubiquitylation of two critical DNA repair substrates : Fanconi anaemia protein (FANCD2) [XREF_BIBR] and proliferating cell nuclear antigen (PCNA) [XREF_BIBR, XREF_BIBR].
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USP1 decreases the amount of PCNA.
| 3
USP1 decreases the amount of PCNA. 3 / 4
| 3
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Notably, exogenous expression of HA tagged C-SDE2 was able to antagonize the elevated PCNA-Ub levels caused by USP1 knockdown and UVC damage, suggesting that activated SDE2 regulates PCNA modification process independently of USP1 (XREF_FIG).
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This decrease in USP1 activity allows PCNA ubiquitylation levels to increase and promote TLS [XREF_BIBR].
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The loss of USP1 activity increases the level of mono-ubiquitinated DNA clamp PCNA, impairing DNA repair.
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USP1 inhibits PCNA.
| 2
USP1 bound to WDR48 inhibits ubiquitinated PCNA. 1 / 1
| 1
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The USP1 and UAF1 complex reduces the accumulation of mono-ubiquitinated PCNA during normal cell division, which prevents mutagenesis by error-prone TLS polymerases.
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USP1 inhibits ubiquitinated PCNA. 1 / 1
| 1
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In addition, in response to H 2 O 2 treatment, we found that USP1 reduced the accumulation of ubiquitinated PCNA but not inhibited NEDDylated PCNA, suggesting that USP1 does not affect PCNA NEDDylation.
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USP1 increases the amount of PCNA.
| 2
USP1 increases the amount of ubiquitinated PCNA. 1 / 1
| 1
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Depletion of Usp1 also elevated the levels of ubiquitinated PCNA after DNA damage (XREF_FIG), suggesting that Usp1 counteracts Rad18 at stressed forks.
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USP1 increases the amount of PCNA. 1 / 1
| 1
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USP1 knockdown or ML-323 treatment reduced the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E1.
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USP1 affects cellular senescence
| 16
USP1 activates cellular senescence.
| 12
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Despite ectopic expression of ID1 or -2, USP1 depleted cells (shUSP1 and ID1 and shUSP1 and ID2) underwent senescence with the same kinetics as control cells depleted for USP1 alone (shC and pBABE [B0[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Together, these data are consistent with the notion that senescence mediated by USP1 depletion does not produce DNA lesions that cause PCNA mono-ubiquitination.
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Finally, we addressed the question of whether or not USP1 mediated senescence is dependent on ID HLH transcription factors.
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Consequently, ID protein overexpression might rescue USP1 mediated senescence by suppressing CDKN1A expression.
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Usp1 depletion failed to induce senescence in the absence of TAp63, whereas Usp1 depletion in wild-type MEFs enhanced cellular senescence.
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If an aberrant localization of FD2-Ub was indeed a gatekeeper for senescence induced by USP1 depletion, then reduced FD2 levels should mitigate the maintenance of senescence upon USP1 depletion.
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Taken together, the data demonstrate that senescence induced by USP1 depletion is associated with a persistent ATR-CHK1-p53-CDKN1A-dependent DDR, perturbed replisome dynamics, and genomic instability,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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These results suggest that senescence compromised cancer cells expressing low levels of USP1 or treatment of cancer cells expressing high levels of USP1 with USP1 inhibitors may be more susceptible to[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Together, these results show p53 and its major transcriptional target CDKN1A to be key factors required for the senescence arrest induced by USP1 depletion.
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Taken together, these data further indicate that depletion of USP1 results in increased cellular levels of FANCD2-Ub, causing increased senescence and decreased epithelial tumor growth in vivo.
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USP1 inhibits cellular senescence.
| 4
USP1 inhibits cellular senescence. 4 / 4
| 4
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In our human fibroblast senescence model, TAp63 upregulation was absent, indicating that acute loss of USP1 function likely produces qualitatively different senescence responses depending on cell type[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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However, in addition to this opposition to activate and monoubiquitinate FANCD2/I, USP1 deubiquitination of FANCI has also been associated with promoting core complex recruitment to the site of DNA da[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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These results suggest that senescence compromised cancer cells expressing low levels of USP1 or treatment of cancer cells expressing high levels of USP1 with USP1 inhibitors may be more susceptible to[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Usp1 knockdown promotes senescence and reduces tumor growth in vivo.
23806336
USP1 affects apoptotic process
| 4 9
USP1 inhibits apoptotic process.
| 4 4
eidos
Recent studies have demonstrated that USP1 inhibition induced apoptosis and suppressed cell proliferation in acute myeloid leukemia ( AML ) and MM cells 12 , 13 .
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Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells.
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USP1 downregulation decreased expressions of fibrosis-related genes , suppressed proliferation , and promoted apoptosis in TGF-beta1-induced LX-2 cells , which were reversed by SNAIL overexpression .
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Similarly, pharmacological inhibition of USP1 by SJB3-019A significantly repressed cell proliferation and triggered B-ALL cell apoptosis.
33390793
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Inhibition of USP1 induces apoptosis via ID1 / AKT pathway in B-cell acute lymphoblastic leukemia cells Deubiquitylating enzyme ubiquitin-specific protease 1 ( USP1 ) has been reported to be aberrantly overexpressed in cancers , and it plays a critical role in regulating various cellular processes , such as cell proliferation , apoptosis , and cell differentiation .
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Inhibition of USP1 induces apoptosis via ID1 and AKT pathway in B-cell acute lymphoblastic leukemia cells.
33390793
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Notably , downregulation of USP1 could inhibit cell proliferation and promote apoptosis in a variety of solid tumors 9,11,12 .
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A recent study demonstrated that USP1 inhibition induces apoptosis in leukemic cells 30.
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USP1 activates apoptotic process.
| 5
USP1 activates apoptotic process. 5 / 6
| 5
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Overexpression of USP1 promoted cell proliferation, apoptosis, migration and invasion, and decreased cell chemo-sensitivity; however, it could be partially reversed via the overexpression of miR-192-5p in osteosarcoma cell lines.
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Our data show that inhibition of USP1 efficiently blocked human beta-cell apoptosis without compromising function.Complex intracellular networks, namely, the DDR, monitor genome integrity and stabilit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 downregulation decreased expressions of fibrosis related genes, suppressed proliferation, and promoted apoptosis in TGF-beta1-induced LX-2 cells, which were reversed by SNAIL overexpression.
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Knockdown of USP1 by siRNA decreased B-ALL cell growth and induced apoptosis.
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Loss of Deubiquitinase USP1 Blocks Pancreatic beta-Cell Apoptosis by Inhibiting DNA Damage Response.
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Pimozide affects USP1
| 12
Pimozide inhibits USP1.
| 7
Pimozide inhibits USP1. 7 / 7
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In this study, we showed that pimozide is a potent inhibitor of a human DUB, USP1 and UAF1, and provided insight into the molecular basis for the antineoplastic activity of pimozide.
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Pimozide and GW7647 inhibit USP1 and UAF1 by a noncompetitive mechanism.
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Another study confirmed that pimozide could inhibit USP1 and in turn decrease the clonal growth of glioblastoma cells as well as increase their sensitivity to irradiation, though they are commonly resistant to chemotherapeutic and irradiation treatments.
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Pimozide and GW7647 inactivate USP1 and UAF1 in cells.
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Another study confirmed that pimozide could inhibit USP1 and in turn decrease the clonal growth of glioblastoma cells as well as increase their sensitivity to irradiation, though they are commonly resistant to chemotherapeutic and irradiation treatments (Lee et al., 2016).
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In order to demonstrate that pimozide and GW7647 inhibit the USP1 and UAF1 activity in cells, we developed an assay to determine the levels of Ub-PCNA or Ub-FANCD2 in cells treated with cisplatin, pimozide and GW7647 or a combination of cisplatin and pimozide and GW7647.
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Further studies of the USP1/UAF1 inhibitors suggested that pimozide and GW7647 inhibit USP1/UAF1 by a non‐competitive mechanism and bind at a site other than the active site of USP1/UAF1 [113].
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Pimozide activates USP1.
| 3
Pimozide activates USP1. 3 / 3
| 3
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The top inhibitors, pimozide and GW7647, blocked USP1 and UAF1 noncompetitively with a Ki of 0.5 and 0.7 muM, respectively, and displayed selectivity against a number of deubiquitinases, deSUMOylase, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
29958636
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The top inhibitors, pimozide and GW7647, inhibited USP1 and UAF1 noncompetitively with a K i of 0.5 and 0.7 muM respectively, and displayed selectivity against a number of deubiquitinases, deSUMOylase and cysteine proteases.
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The most potent inhibitors, pimozide and GW7647, inhibited USP1 and UAF1 reversibly with a micromolar IC 50.
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Pimozide decreases the amount of USP1.
| 2
Pimozide decreases the amount of USP1. 2 / 2
| 2
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Importantly, pimozide lowered USP1 levels, triggered ID1 degradation and inhibited K562 cell growth in vitro and in vivo (Mistry et al., 2013).
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Interestingly, Pimozide promoted ID1 degradation, decreased USP1 levels, and caused a dose dependent inhibition of K562 cell growth in vitro with induction of apoptosis (XREF_FIG), though at a higher drug concentrations as compared to SJB2-043.
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USP1 affects Ubiquitin
| 9
USP1 inhibits Ubiquitin.
| 5
USP1 inhibits Ubiquitin. 4 / 6
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In the past year, two other deubiquitinating enzymes, USP27X and USP1, have been reported to impede ubiquitin mediated degradation of Snail1 in various biological contexts XREF_BIBR, XREF_BIBR.
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We therefore reasoned that pharmacologic inhibition of USP1 would promote ubiquitin mediated degradation of ID1 protein, resulting in differentiation and growth inhibition of immature leukemic cells.
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However, a structural relationship to ubiquitin has been recently proposed for human USP1, which is inactivated by auto‐cleavage after an internal ubiquitin‐like di‐glycine motif.
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Wild-type USP1, but not USP1 C90S, reduced the amount of ID2 modified with HA tagged ubiquitin.
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USP1-C90S inhibits Ubiquitin. 1 / 1
| 1
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Wild-type USP1, but not USP1 C90S, reduced the amount of ID2 modified with HA tagged ubiquitin.
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USP1 activates Ubiquitin.
| 4
USP1 activates Ubiquitin. 4 / 4
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The specificity of SJB was confirmed by various experiments : first, we show that SJB potently and selectively block USP1 activity without inhibiting other DUBs (USP2/USP5/USP7/USP14/UCH37); second, SJB inhibited binding of USP1 with HA-Ub-VS probe, but it did not affect labeling of other DUBs with probe; and third, SJB inhibited USP1, but not USP2 or USP7, triggered cleavage of ubiquitin tetramer chains.
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Interestingly, the ubiquitin removal from both PCNA and FANCD2 and FANCI is mediated by the same deubiquitinating enzyme USP1 [86,125] and is required for successful DNA crosslink repair [126].
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Furthermore, when we depleted USP1, which has been shown to increase endogenous ubiquitin conjugated PCNA species, an increased level of ubiquitylated PCNA could be pulled down by Spartan (XREF_FIG C).
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The WD-repeat protein WDR48 (USP1 associated factor UAF-1) stimulates activity of ubiquitin specific proteases USP1, USP12, and USP46.
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USP1 affects CHEK1
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USP1 activates CHEK1.
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USP1 activates CHEK1. 5 / 6
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USP1 limits DDB1 dependent degradation of CHK1.
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Finally, to ascertain if elements other than mono-Ub-FANCD2 participate in USP1 mediated CHK1 downregulation, we depleted USP1 in FA-C, FA-G and FA-D2 fibroblasts.
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Two E3 ligase complexes, CUL4A and DDB1 and CUL1 and FBXO6, have shown to be responsible for Chk1 polyubiquitination and degradation; whereas deubiquitinases (DUB), USP1 and USP7, have been reported to promote Chk1 stabilization.
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USP1 enhanced protein stability of the ID1 and CHEK1, important regulators of DNA damage response and stem cell maintenance (Lee et al., 2016).
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It has been previously reported that deubiquitinase USP1 maintains both total and phosphorylated Chk1 level and that USP1 deletion promotes degradation of activated Chk1 in a DDB1 dependent manner.
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USP1 inhibits CHEK1.
| 1
USP1 inhibits CHEK1. 1 / 3
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Other USP1 activities include involvement in a feedback loop to limit DDR CHK1 protein kinase activity 72 , and the regulation of cellular differentiation in osteosarcoma cells by deubiquitylating and hence affecting the stability of inhibitors of DNA-binding proteins 73 .
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USP1 increases the amount of CHEK1.
| 1
USP1 increases the amount of CHEK1. 1 / 1
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Co-depletion of USP1, together with the FANCcore complex proteins FANCC or FANCD2, rescued the steady-state level of CHK1.
21389083
USP1 affects FANCI
| 6
USP1 decreases the amount of FANCI.
| 2
USP1 decreases the amount of FANCI. 1 / 3
| 1
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We found that USP1 inhibition by SJB increased the levels of both Ub-FANCD2 and Ub-FANCI in MM cells.
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USP1 bound to WDR48 decreases the amount of FANCI. 1 / 1
| 1
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Disruption of USP1/UAF1 complex promote level of FANCD2/FANCI ubiquitination and DNA repair defects, suggesting a failure in the completion of FA pathway (Nijman et al., 2005b, Smogorzewska et al., 2007).
27211605
USP1 inhibits FANCI.
| 2
USP1 inhibits FANCI. 2 / 3
| 2
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However, in FA pathway, disruption of USP1 gene causes accumulation of the monoubiquitinated forms of FANCD2 and FANCI but increases ICL hypersensitivity and genomic instability [XREF_BIBR, XREF_BIBR].
27398234
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However, in FA pathway, disruption of USP1 gene causes accumulation of the monoubiquitinated forms of FANCD2/FANCI but increases ICL hypersensitivity and genomic instability [49, 77] .
27398234
USP1 activates FANCI.
| 2
USP1 activates FANCI. 1 / 2
| 1
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In addition, DUBs involved in DNA damage signaling are USP1 that targets PCNA (proliferating cell nuclear antigen) [76], FANCD2 and FANCI (the Fanconi anemia proteins) [93,94], and USP3 and USP16 that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 activates ubiquitinated FANCI. 1 / 1
| 1
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Alternatively, USP1 deficiency may cause the accumulation of monoubiquitinated FANCI at genomic sites away from DNA damage, where it can not undergo S559 and S565 phosphorylation by ATR.
28636932
USP1 affects WDR48
| 8
USP1 activates WDR48.
| 6
USP1 activates WDR48. 6 / 7
| 6
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The possibility that the NLS inactivating mutations might simultaneously interfere with UAF1 binding can not be formally ruled out, but these results suggest that the inability of USP1 (235-408) to promote UAF1 relocation can not be ascribed to competition with the nuclear import machinery.
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USP1, the major DUB of FANCD2 and FANCI, inactivates these two proteins mediated by the USP1 activating factor UAF1 once DNA damage repair is finished [XREF_BIBR].
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This assay is based on the nuclear accumulation of UAF1 induced by USP1 co-expression and, by using fluorescently tagged versions of these proteins, the results can be observed in live cells, before processing for microscopy analysis.
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Moreover, we verified that (i) UAF1-USP1 is no more effective than UAF1 in the D-loop reaction (XREF_SUPPLEMENTARY), and (ii) USP1 fails to restore functional synergy of the UAF1 EEA mutant with RAD51AP1 (XREF_SUPPLEMENTARY).
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Further studies of the USP1/UAF1 inhibitors suggested that pimozide and GW7647 inhibit USP1/UAF1 by a non‐competitive mechanism and bind at a site other than the active site of USP1/UAF1 [113].
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Moreover, we verified that UAF1-USP1 is no more effective than UAF1 in the D-loop reaction and that USP1 fails to restore functional synergy of the UAF1 EEA mutant with RAD51AP1.
27239033
USP1 inhibits WDR48.
| 2
USP1-E444K inhibits WDR48. 1 / 1
| 1
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Likewise, mutation of USP1 E444K, analogous to the impactful USP46 E186K mutation, abrogated WDR48 binding and stimulation of USP1 deubiquitinase activity.
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USP1 inhibits WDR48. 1 / 1
| 1
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An analogous mutation in USP1 similarly blocked WDR48 dependent activation.
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GW 7647 affects USP1
| 8
GW 7647 inhibits USP1.
| 5
GW 7647 inhibits USP1. 5 / 5
| 5
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Although two inhibitors namely pimozide and GW7647 were reported to selectively inhibit USP1 and UAF1, they also inhibited other DUBs, deSUMOlyase and cysteine proteases [XREF_BIBR].
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Pimozide and GW7647 inactivate USP1 and UAF1 in cells.
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Further studies of the USP1/UAF1 inhibitors suggested that pimozide and GW7647 inhibit USP1/UAF1 by a non‐competitive mechanism and bind at a site other than the active site of USP1/UAF1 [113].
24239534
reach
Pimozide and GW7647 inhibit USP1 and UAF1 by a noncompetitive mechanism.
22118673
reach
In order to demonstrate that pimozide and GW7647 inhibit the USP1 and UAF1 activity in cells, we developed an assay to determine the levels of Ub-PCNA or Ub-FANCD2 in cells treated with cisplatin, pimozide and GW7647 or a combination of cisplatin and pimozide and GW7647.
22118673
GW 7647 activates USP1.
| 3
GW 7647 activates USP1. 3 / 3
| 3
reach
The top inhibitors, pimozide and GW7647, inhibited USP1 and UAF1 noncompetitively with a K i of 0.5 and 0.7 muM respectively, and displayed selectivity against a number of deubiquitinases, deSUMOylase and cysteine proteases.
22118673
reach
The most potent inhibitors, pimozide and GW7647, inhibited USP1 and UAF1 reversibly with a micromolar IC 50.
23797609
reach
The top inhibitors, pimozide and GW7647, blocked USP1 and UAF1 noncompetitively with a Ki of 0.5 and 0.7 muM, respectively, and displayed selectivity against a number of deubiquitinases, deSUMOylase, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
29958636
USP1 affects KDM4A
| 1 7
USP1 increases the amount of KDM4A.
| 5
USP1 increases the amount of KDM4A. 4 / 4
| 4
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USP1 knockdown in RV1, LNCAP, and PC3 cells significantly decreased KDM4A protein level, but did not affect KDM4A mRNA level.
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As shown in Figure XREF_FIG, USP1 knockdown dramatically reduced levels of KDM4A and c-Myc, whereas the reconstitution of KDM4A was able to efficiently rescue their expression.
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Similarly, USP1 knockdown in RV1 cells using 2 specific shRNAs significantly decreased KDM4A protein levels and increased cellular sensitivity to enzalutamide treatment, whereas overexpression of KDM4A in depleted cells with USP1 reversed hypersensitivity to enzalutamide treatment.
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We previously found that USP1 knockdown decreased levels of KDM4A in PC cells.
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Modified USP1 increases the amount of KDM4A. 1 / 1
| 1
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Furthermore, overexpression of WT USP1 but not the catalytic inactive mutant (CS mutant) in RV1 cells could dramatically increase KDM4A protein level in the cells with depletion of USP1.
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USP1 activates KDM4A.
| 1 2
USP1 activates KDM4A. 3 / 3
| 1 2
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We observed that the USP1 inhibitor promoted KDM4A degradation ( Figure7D ) .
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Taken together, these results suggest that USP1 directly regulates KDM4A stability.
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Furthermore, we found that USP1 overexpression decreased the polyubiquitination levels in WT, K6R, K11R, K27R, K29R, K33R, and K63R HA-ubiquitin mutants but not in K48R mutant, suggesting USP1 promotes KDM4A K48 linked deubiquitin; however, which E3 ubiquitin ligase mediated KDM4A ubiquitin and degradation is still unclear.
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USP1 affects CDKN1A
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USP1 inhibits CDKN1A.
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USP1 inhibits CDKN1A. 2 / 2
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Taken together, our results demonstrate that USP1 suppresses p21 via ID protein stabilization and inhibition of bHLH transcriptional activity in osteosarcoma.Osteosarcomas are heterogeneous tumors com[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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shRNA resistant wild-type USP1, but not USP1 C90S, reduced p21 to levels observed in control cells, confirming knockdown specificity in this setting.
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USP1-C90S inhibits CDKN1A. 1 / 1
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shRNA resistant wild-type USP1, but not USP1 C90S, reduced p21 to levels observed in control cells, confirming knockdown specificity in this setting.
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USP1 increases the amount of CDKN1A.
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USP1 increases the amount of CDKN1A. 2 / 2
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In wild-type MEFs, Usp1 depletion increased the levels of Fancd2-Ub, TAp63, and p21 (XREF_FIG, lanes 1, 2) and enhanced OIS (XREF_FIG).
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In contrast, Usp1 depletion failed to induce TAp63 or p21 expression levels and only slightly induced senescence in Fancd2 (-/-) MEFs.
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USP1 activates CDKN1A.
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USP1 activates CDKN1A. 2 / 2
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Increased USP1 levels were also observed upon siRNA mediated p21 depletion (see XREF_FIG, lanes 5 and 6).
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Significantly, CDKN1A siRNAs restored S phase entry in USP1 deficient U2-OS cells, indicating that p21 is essential for the cell-cycle arrest induced by USP1 knockdown.If ID degradation in the absence[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 decreases the amount of CDKN1A.
| 1
Modified USP1 decreases the amount of CDKN1A. 1 / 1
| 1
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USP1 was overexpressed frequently in primary osteosarcomas and osteosarcoma cell lines, and by deubiquitinating the ID proteins, inhibited bHLH dependent expression of CDKI p21 resulting in unchecked [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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USP1 activates Neoplasm Metastasis.
| 6
USP1 activates Neoplasm Metastasis. 6 / 6
| 6
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USP1 Promotes GC Metastasis via Stabilizing ID2.
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USP1 dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells.
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USP1 inhibition destabilizes KPNA2 and suppresses breast cancer metastasis.
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In conclusion, our study showed that USP1 promoted GC metastasis via stabilizing ID2 expression, which provides a potential biomarker and therapy target for GC.
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Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC.
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Then, real-time cellular analysis (RTCA) showed that USP1 knockdown inhibited GC metastasis both in vitro and in vivo.
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USP1 inhibits Neoplasm Metastasis.
| 1
reach
Most importantly, pharmacological intervention of USP1 function by pimozide or ML323 significantly represses breast cancer metastasis in mice, suggesting a rationale for using USP1 inhibitors for treatment of patients with breast cancer.
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USP1 affects DNA repair
| 7
USP1 activates DNA repair.
| 4
USP1 activates DNA repair. 4 / 4
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Usp1 modulates DNA replication, polymerase choice and DNA repair by PCNA and as a result Usp1 knock-out mice are genetically unstable and hypersensitive to DNA damage [XREF_BIBR], [XREF_BIBR].
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Because CHK1 is a cell cycle regulated and DNA damage checkpoint protein, we asked whether (a) the downregulation of CHK1 in USP1 depleted cells is an experimental artefact resulting from modifications of the cell cycle and/or altered DNA repair capabilities caused by USP1 depletion and (b) USP1 depletion modifies the G2 checkpoint in response to DNA damage.
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The deubiquitinating enzyme, USP1 is known to promote DNA repair via complexing with UAF1.
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Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells.
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USP1 inhibits DNA repair.
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USP1 inhibits DNA repair. 2 / 2
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Initial evidence suggested that USP1 inhibition leads to constitutive DNA repair and protects cells from MMC induced chromosome aberrations [45].
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Mutation of aspartic acid 199 in USP1 disrupts its deubiquitinating activity and impairs DNA repair.
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USP1 bound to WDR48 inhibits DNA repair. 1 / 1
| 1
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Disruption of USP1/UAF1 complex promote level of FANCD2/FANCI ubiquitination and DNA repair defects, suggesting a failure in the completion of FA pathway (Nijman et al., 2005b, Smogorzewska et al., 2007).
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PCNA affects USP1
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PCNA activates USP1.
| 3
PCNA activates USP1. 3 / 3
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Usp1 modulates DNA replication, polymerase choice and DNA repair by PCNA and as a result Usp1 knock-out mice are genetically unstable and hypersensitive to DNA damage [XREF_BIBR], [XREF_BIBR].
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However, pathway (s) responsible for the regulation of USP1 as well as the molecular mechanism by which USP1 regulates DDR in beta-cells, especially in the diabetic environment, remains unknown and wa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Similar results have been seen in the case of Usp1 and Uaf -1 where knockdown of either protein alone altered the ubiquitination status of Usp1 targets PCNA and FANCD2, in this example an epistatic relationship between Usp1 and Uaf-1 was observed [XREF_BIBR].
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PCNA inhibits USP1.
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PCNA inhibits USP1. 2 / 2
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USP1 dependent PCNA deubiquitylation is regulated, on one hand, by UV irradiation dependent inactivation of USP1 through an autocleavage event and, on the other hand, by the PCNA interacting ELG1 protein that is essential for recruiting USP1-UAF1 to the stalled fork.
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(2) PCNA deubiquitination to limit the DNA damage bypass pathway by recruiting the USP1 and USP1 associated factor 1 (UAF1) complex [XREF_BIBR].
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PCNA deubiquitinates USP1.
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PCNA deubiquitinates USP1. 2 / 2
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To provide additional confirmation, we aimed to test the effect of decreasing the level of ubiquitin conjugated PCNA, which can be carried out by expressing the PCNA deubiquitylating enzyme USP1 as described.
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XREF_BIBR The levels of PCNA modification are additionally controlled by the clamp loader Elg1, which binds to and unloads sumoylated PCNA from chromatin in yeast XREF_BIBR and targets the PCNA deubiquitinating enzyme USP1 to replicative DNA lesions in humans.
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USP1 affects USP1
| 5
USP1 decreases the amount of USP1.
| 2
USP1 decreases the amount of USP1. 2 / 3
| 2
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A doxycycline induced USP1 shRNA suppressed USP1 expression and reduced ID1 and ID2 in the xenografts.
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The important regulatory role of USP1 in DNA repair, supported by the finding that USP1 gene knockout in model systems leads to DNA damage hypersensitivity [XREF_BIBR - XREF_BIBR], together with the observation that USP1 is frequently overexpressed in tumors, suggests that USP1 could be a relevant target for cancer therapy, whose inhibition might contribute to overcome chemoresistance.
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USP1 activates USP1.
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USP1 activates USP1. 1 / 2
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In addition, USP1 overexpression activated phosphoinositide 3-kinase (PI3K) signaling, whereas a selective PI3K inhibitor (S2739) could reverse the effects of USP1 on NPC cells in vitro.
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USP1 bound to WDR48 activates USP1. 1 / 1
| 1
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Several studies showed that UAF1 forms a complex with USP1 and stimulates the deubiquitination activity of USP1 both in vitro and in vivo.
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USP1 increases the amount of USP1.
| 1
USP1 increases the amount of USP1. 1 / 1
| 1
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The important regulatory role of USP1 in DNA repair, supported by the finding that USP1 gene knockout in model systems leads to DNA damage hypersensitivity [XREF_BIBR - XREF_BIBR], together with the observation that USP1 is frequently overexpressed in tumors, suggests that USP1 could be a relevant target for cancer therapy, whose inhibition might contribute to overcome chemoresistance.
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SJB2-043 affects USP1
1 | 5
SJB2-043 inhibits USP1. 6 / 6
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USP1 inhibitor SJB2-043 inhibits the enzyme activity of native USP1.
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We next determined whether SJB2-043 inhibits the DUB activity of native USP1 complexes isolated from human cells (XREF_FIG).
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SJB2-043 blocked the deubiquitinating enzyme activity of USP1 in vitro with an IC50 in the nanomolar range (Mistry et al., 2013).
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No evidence text available
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These results demonstrate that USP1 inhibitor SJB2-043 inactivates native USP1 in primary AML cells and exhibits cytotoxicity.
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In addition, SJB2-043 inhibited the labeling of USP1 with Ub-VS in a dose dependent manner (XREF_SUPPLEMENTARY).
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Phenethyl isothiocyanate inhibits USP1.
| 2 2
Phenethyl isothiocyanate inhibits USP1. 4 / 4
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We confirmed the inhibition of USP1 by PEITC by monitoring the hydrolysis of di-Ub by purified USP1 in complex with its activator UAF1.
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PEITC treatment decreased the ratio of labeled to unlabeled USP1, demonstrating that PEITC inhibits USP1 in living cells.
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We confirmed the inhibition of USP1 by PEITC by monitoring the hydrolysis of di-Ub by purified USP1 in complex with its activator UAF1 (Figure xref ).
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PEITC treatment decreased the ratio of labeled to unlabeled USP1, demonstrating that PEITC inhibits USP1 in living cells (Figure xref and xref ).
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Phenethyl isothiocyanate decreases the amount of USP1.
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Phenethyl isothiocyanate decreases the amount of USP1. 2 / 2
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PEITC decreases USP1 levels.
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Surprisingly, PEITC also decreased total USP1 protein levels in a dose dependent manner.
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USP1 activates Neoplasm Invasiveness.
| 4
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Gene silencing of USP1 by lentivirus effectively inhibits proliferation and invasion of human osteosarcoma cells.
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It remains to be investigated if our small molecule inhibitors of USP1 can reduce the invasiveness of leukemic cells.
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USP1 enhances the expression of a number of pro metastatic genes in breast cancer cells, promotes cell migration and invasion in vitro, and facilitates lung metastasis of breast cancer cells.
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Overexpression of USP1 promoted cell proliferation, apoptosis, migration and invasion, and decreased cell chemo-sensitivity; however, it could be partially reversed via the overexpression of miR-192-5p in osteosarcoma cell lines.
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USP1 inhibits Neoplasm Invasiveness.
| 2
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Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin associated infiltration in vivo.
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USP1 inhibits Neoplasm Invasiveness. 1 / 1
| 1
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Collectively, our results suggest that silencing USP1 inhibits cell proliferation and invasion in U2OS cells.
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USP1 affects ID2
| 6
USP1 activates ID2.
| 3
USP1 activates ID2. 3 / 3
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USP1 knockdown specificity was confirmed with shRNA resistant USP1, which restored ID1, ID2, and ID3 to basal levels.
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A doxycycline induced USP1 shRNA suppressed USP1 expression and reduced ID1 and ID2 in the xenografts.
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Mechanistically, we found that PDGF signaling regulated the expression of the E2F transcription factors, which directly bound to and activated Usp1 Furthermore, PDGF mediated expression of USP1 led to the stabilization of Inhibitor of DNA binding 2 (ID2), which we found to be required for glioma cell survival.
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USP1 decreases the amount of ID2.
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USP1 decreases the amount of ID2. 1 / 1
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Usp1 deficiency resulted in a gradual loss of memory CD8 + T cells over time and reduced Id2 protein levels and proliferation of effector CD8 + T cell following reinfection.
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USP1 decreases the amount of ubiquitinated ID2. 1 / 1
| 1
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In keeping with this scenario, USP1 knockdown in MG-132-treated U2-OS cells increased the amount of ubiquitinated ID2.
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USP1 inhibits ID2.
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USP1 inhibits ID2. 1 / 1
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A doxycycline induced USP1 shRNA suppressed USP1 expression and reduced ID1 and ID2 in the xenografts.
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Methoprene affects USP1
| 5
Methoprene increases the amount of USP1.
| 3
Methoprene increases the amount of USP1. 3 / 3
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Simultaneously, RNAi of HaCal suppressed the transcript levels of USP1, PKC, and JHi but not of Met1 and Br-Z2 induced by methoprene in the JH signaling (lane O compared to I).
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Knockdown of Met1 suppressed the transcript levels of USP1, PKC, HaCal, and JHi induced by methoprene (lane L compared to I).
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However, the transcript levels of USP1, PKC, and Br-Z2 induced by methoprene were not suppressed (lane J compared to I).
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Methoprene activates USP1.
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Methoprene activates USP1. 2 / 2
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USP1, PKC, Br-Z2, and HaCal were induced by both 20E and methoprene.
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In the methoprene treated cells, the non phosphorylated calponin bound with USP1 was necessary for methoprene induced USP1 up-regulation along with that of JHi.
21625546
USP1 inhibits Genomic Instability.
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USP1 inhibits Genomic Instability. 3 / 3
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However, in addition to this opposition to activate and monoubiquitinate FANCD2/I, USP1 deubiquitination of FANCI has also been associated with promoting core complex recruitment to the site of DNA da[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Controlling the ubiquitylation of these two key players appears to be essential for proper replication fork maintenance, as loss of USP1 causes high levels of genome instability and mutagenesis.
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However, in FA pathway, disruption of USP1 gene causes accumulation of the monoubiquitinated forms of FANCD2 and FANCI but increases ICL hypersensitivity and genomic instability [XREF_BIBR, XREF_BIBR].
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USP1 activates Genomic Instability.
| 2
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Interestingly, siRNA mediated knock-down of FAN1 and USP1, the enzyme responsible for deubiquitylating PCNA, caused similar genomic instability in U2OS cells, but the number of DSBs in the double knock-down was increased approximately two-fold, thus indicating that an increase in ub-PCNA may worsen the genomic instability in FAN1 depleted cells.
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It is tempting to speculate that USP1 deficiency preferably produces replication stress and genomic instability at fragile sites.
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USP1 affects BRCA1
| 5
USP1 activates BRCA1.
| 4
USP1 activates BRCA1. 4 / 4
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In contrast to the overexpression, the depletion of USP1 increased the number of BRCA1 foci but decreased the number of RIF1 foci in S/G2 cells (XREF_FIG, XREF_SUPPLEMENTARY).
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As expected, the number of BRCA1 foci reduced dramatically in Cdh1 depleted cells treated with HU, and the simultaneous depletion of USP1 with that of Cdh1 essentially restored BRCA1 focus number (XREF_FIG).
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As shown in XREF_FIG, the depletion of USP1 in control cells (no ectopic USP1 expression) expectedly caused an increase of BRCA1 IRIF but a decrease of RIF1 IRIF (as seen in XREF_FIG).
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Knockdown or inhibition of USP1 resulted in replication fork destabilization and decreased viability of BRCA1 deficient cells, revealing a synthetic lethal relationship.
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USP1 inhibits BRCA1.
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USP1 inhibits BRCA1. 1 / 1
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Given that USP1 suppresses BRCA1, we expect that compromising APC function would also lead to an apparent suppression on BRCA1 focus formation.
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USP1 affects TBK1
| 5
USP1 increases the amount of TBK1.
| 4
USP1 increases the amount of TBK1. 3 / 3
| 3
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Among the USP members, USP1 functions as a viral infection-induced physiological enhancer of TBK1 expression when bound to USP1 the K48-linked polyubiquitination of TBK1, resulting in enhanced TLR3/4 and RIG-I-induced IRF3 activation and IFNβ secretion (74).
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Consistently, UAF1 and USP1 knockdown also significantly decreased TBK1 protein level in both SeV- and LPS stimulated macrophages (XREF_FIG).
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Among the USP members, USP1 functions as a viral infection-induced physiological enhancer of TBK1 expression when bound to USP1 the K48-linked polyubiquitination of TBK1, resulting in enhanced TLR3/4 and RIG-I-induced IRF3 activation and IFNb secretion (74) .
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Modified USP1 increases the amount of TBK1. 1 / 1
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UAF1 and USP1 overexpression both greatly enhanced TBK1 protein expression in a dose dependent manner in HEK293T cells, with no effects on IRF3 expression (XREF_FIG).
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USP1 activates TBK1.
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USP1 bound to WDR48 activates TBK1. 1 / 1
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To further investigate whether USP1 and UAF1 complex could inhibit TBK1 protein degradation, a cycloheximide (CHX) chase experiment was performed.
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Tamoxifen affects USP1
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Tamoxifen activates USP1. 4 / 4
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By radioimmune precipitation assay of [35S] methionine labeled uterine luminal fluid proteins, it was shown that tamoxifen and LY117018 could weakly induce USP-1 compared with E2.
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Peptide-N-glycosidase treatment of USP-1 induced by E2 or tamoxifen removed asparagine linked carbohydrate chains and resulted in the appearance of polypeptides with apparent mol wt of 91K and 105K, respectively.
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Thus, the higher mol wt of tamoxifen induced USP-1 is not due to changes in asparagine linked carbohydrates.
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Sodium dodecylsulfate-polyacrylamide gel analysis of immunoprecipitable [35S] methionine labeled protein revealed that USP-1 induced by tamoxifen is larger (110K) than that induced by estrogen or LY117018 (97K).
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USP1 affects Stomach Neoplasms
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USP1 Promotes GC Metastasis via Stabilizing ID2.
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Then, real-time cellular analysis (RTCA) showed that USP1 knockdown inhibited GC metastasis both in vitro and in vivo.
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Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC.
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In conclusion, our study showed that USP1 promoted GC metastasis via stabilizing ID2 expression, which provides a potential biomarker and therapy target for GC.
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FANCD2 affects USP1
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FANCD2 activates USP1. 4 / 4
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Deubiquitylation of FANCD2 and FANCI is mediated by the ubiquitin specific peptidase 1 (USP1) and USP1 associated factor 1 (UAF1; also known as WDR48) complex 73.
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USP1 targets FANCD2, FANC1, and PCNA for deubiquitylation.
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However, pathway (s) responsible for the regulation of USP1 as well as the molecular mechanism by which USP1 regulates DDR in beta-cells, especially in the diabetic environment, remains unknown and wa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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In USP1 depleted cells this fraction is also enriched in SQSTM1 (sequestosome 1), the aggresome marker HDAC6 (histone deacetylase 6), and the prototype of USP1 targets FANCD2 (FA complementation group D2).
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USP1 bound to WDR48 activates homologous recombination. 2 / 2
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A study in which USP1 -/-, UAF1 -/-/-, and USP1 -/- UAF1 -/-/- double-knockout DT40 cells showed hypersensitivity to camptothecin and an inhibitor of poly (ADP-ribose) polymerase (PARP), which suggests that the USP1 and UAF1 complex promotes HR.
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Additionally, the same study disrupted the NHEJ pathway, via knockout of Ku70 (also known as XRCC6 or X-Ray repair cross complementing 6), in UAF1 -/-/- cells which restored the cellular resistance to camptothecin and the PARP inhibitor suggesting that the USP1 and UAF1 complex promotes HR, at least in part by suppressing NHEJ.
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USP1 activates homologous recombination. 2 / 2
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In contrast, inhibition of USP1 by ML323 decreased the I-SceI-induced HR frequency to 0.81% (XREF_FIG and XREF_SUPPLEMENTARY).
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However, the direct mechanism by which USP1 and UAF1 promotes HR remains to be elucidated [XREF_BIBR].
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USP1 affects TP53BP1
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USP1 inhibits TP53BP1.
| 1
USP1 inhibits TP53BP1. 1 / 3
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Strikingly, ectopic coexpression of USP1 and UAF1 depleted conjugated ubiquitin in the nucleus and blocked the recruitment of 53BP1 to DNA damage foci.
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USP1 activates TP53BP1.
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USP1 activates TP53BP1. 1 / 1
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To our interest, USP1 reportedly destroys K63 linked polyubiquitin chains on histones and then promotes to recruit 53BP1 at DNA damage sites; another previous report found that KDM4A regulates DNA repair by controlling the recruitment of 53BP1 at DNA damage sites and RNF8 dependent degradation of KDM4A regulates DNA repair by controlling the recruitment of 53BP1 at DNA damage sites.
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USP1 affects MYC
| 1 3
USP1 increases the amount of MYC.
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USP1 increases the amount of MYC. 2 / 2
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As shown in Figure XREF_FIG, USP1 knockdown dramatically reduced levels of KDM4A and c-Myc, whereas the reconstitution of KDM4A was able to efficiently rescue their expression.
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Taken together, these results indicate that USP1 promotes the expression of c-Myc by regulating KDM4A.
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USP1 activates MYC.
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USP1 activates MYC. 2 / 2
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We found that R1881 induced a significant increase in NKX3.1 (a positive control) transcript in RV1 cells, but it failed to induce the c-Myc transcript, and USP1 knockdown reduced the c-Myc or NKX3.1 transcript similarly, with or without R1881.
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Taken together , these results indicate that USP1 promotes the expression of c-Myc by regulating KDM4A .
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As DDR markers are highly elevated in human and rodent diabetic islets and beta-cells in vitro and in vivo and correlate with beta-cell death (Belgardt et al., 2015; Himpe et al., 2016; Nyblom et al.,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Other USP1 activities include involvement in a feedback loop to limit DDR CHK1 protein kinase activity 72 , and the regulation of cellular differentiation in osteosarcoma cells by deubiquitylating and hence affecting the stability of inhibitors of DNA-binding proteins 73 .
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To further test the efficacy of USP1 inhibition to suppress DDR, we quantified the number of p-p53 (at Ser15)-positive beta-cells in isolated human islets treated with USP1 inhibitors exposed to the d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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In this respect, it would be interesting to see whether USP1 depletion in MEFs induces a DDR and replication stress.A recent study reported that FD2 depletion in human cells induces replication stress[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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ID1 affects USP1
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ID1 activates USP1.
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ID1 activates USP1. 3 / 3
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Importantly, ID1 is downstream target of USP1 31.
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Collectively, these data suggest that ID protein stabilization by USP1 in osteosarcoma blocks a normal osteogenic differentiation program.The potential of USP1 inhibition as a tumor differentiation st[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Significantly, CDKN1A siRNAs restored S phase entry in USP1 deficient U2-OS cells, indicating that p21 is essential for the cell-cycle arrest induced by USP1 knockdown.If ID degradation in the absence[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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ID1 inhibits USP1.
| 1
ID1 inhibits USP1. 1 / 1
| 1
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Small molecule inhibitors of USP1 target ID1 degradation in leukemic cells.
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FANCI affects USP1
| 4
FANCI inhibits USP1.
| 3
FANCI inhibits USP1. 3 / 3
| 3
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Then FANCI phosphorylation by ATR probably limits access of USP1 (but not the core complex), leading to mono-ubiquitinated FANCD2 and FANCI complex with a higher affinity to damaged chromatin.
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This idea is fascinating, and suggests that FANCI phosphorylation is actually functioning to suppress USP1 de-ubiquitinase access rather than triggering activation of the E3 ligase FANCL.Interestingly[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Conversely, FANCI phosphorylation reportedly impedes activity of the cognate deubiquitinating enzyme USP1 35, thus favouring the ubiquitinated state.
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FANCI activates USP1.
| 1
FANCI activates USP1. 1 / 1
| 1
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Deubiquitylation of FANCD2 and FANCI is mediated by the ubiquitin specific peptidase 1 (USP1) and USP1 associated factor 1 (UAF1; also known as WDR48) complex 73.
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USP1 affects cell growth
| 1 2
USP1 inhibits cell growth. 3 / 3
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Knockdown of USP1 by siRNA decreased B-ALL cell growth and induced apoptosis.
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Interestingly, Pimozide promoted ID1 degradation, decreased USP1 levels, and caused a dose dependent inhibition of K562 cell growth in vitro with induction of apoptosis (XREF_FIG), though at a higher drug concentrations as compared to SJB2-043.
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Pimozide is a USP1 inhibitor that inhibits leukemic cell growth through degradation of ID1 proteins [ xref ].
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TFDP1 affects USP1
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TFDP1 decreases the amount of USP1. 3 / 3
3 |
biopax:msigdb
No evidence text available
biopax:msigdb
No evidence text available
biopax:msigdb
No evidence text available
Proteasome affects USP1
| 3
Proteasome inhibits USP1. 3 / 3
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Upon UV DNA damage, USP1 is auto-cleaved and degraded by the proteasome.
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First, transcription of the USP1 gene is turned off, and second, the USP1 protein present in the cells is quickly degraded by the proteasome, in a process that appears to be initiated by an endo-proteolytic cleavage (possibly autocleavage) at an internal GG motif of USP1.
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USP1 gets cleaved, and subsequently degraded by the proteasome system in response to UV light exposure, but not to alkylating or cross linking agents [XREF_BIBR, XREF_BIBR].
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Parkinson Disease affects USP1
| 3
Parkinson Disease inhibits USP1. 3 / 3
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PD inhibits USP1/UAF1 activity with an IC50 value of 2.536e-005 M (Figure 4C).
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An in vitro assay with purified rDUB showed that PD inhibited USP1/ is shown by multi-gauge software (Fuji).
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An in vitro assay with purified rDUB showed that PD inhibited USP1/UAF1 activity.
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ML-323 affects USP1
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ML-323 inhibits USP1. 3 / 3
2 | 1
tas
No evidence text available
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No evidence text available
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USP1 was knocked down with small interfering RNA (siRNA) or pharmacologically inhibited by ML-323 in MHCC97H or SK-Hep-1 cell lines for function analysis.
32951278
17alpha-ethynylestradiol increases the amount of USP1. 3 / 3
3 |
ctd
No evidence text available
17942748
ctd
No evidence text available
24096037
ctd
No evidence text available
23129252
Succimer affects USP1
3 |
Succimer decreases the amount of USP1.
2 |
Succimer decreases the amount of USP1. 2 / 2
2 |
ctd
No evidence text available
26378955
ctd
No evidence text available
21641980
Succimer increases the amount of USP1.
1 |
Succimer increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
26378955
Magnetite nanoparticle decreases the amount of USP1.
2 |
Magnetite nanoparticle decreases the amount of USP1. 2 / 2
2 |
ctd
No evidence text available
26378955
ctd
No evidence text available
21641980
Magnetite nanoparticle increases the amount of USP1.
1 |
Magnetite nanoparticle increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
26378955
Benzo[a]pyrene affects USP1
3 |
Benzo[a]pyrene decreases the amount of USP1.
2 |
Benzo[a]pyrene decreases the amount of USP1. 2 / 2
2 |
ctd
No evidence text available
22228805
ctd
No evidence text available
22316170
Benzo[a]pyrene increases the amount of USP1.
1 |
Benzo[a]pyrene increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
22228805
USP1 affects DNA Damage
| 3
USP1 activates DNA Damage.
| 2
USP1 activates DNA Damage. 2 / 2
| 2
reach
Low levels of Usp1 in G1 allow an efficacious monoubiquitylation of PCNA in response to UV mediated DNA damage before DNA replication.
23159736
reach
Furthermore, the USP1 protein itself is reported to undergo rapid degradation in human cells after UV induced DNA damage.
18082605
USP1 inhibits DNA Damage.
| 1
USP1 inhibits DNA Damage. 1 / 1
| 1
reach
Because USP1 is reported to target PCNA and FANCD2 during DNA repair (Nijman et al., 2005; Huang et al., 2006), we also checked if USP1 knockdown produced DNA damage.
21925315
CDH1 affects USP1
| 3
CDH1 inhibits USP1.
| 1
CDH1 inhibits USP1. 1 / 1
| 1
reach
We found that a region surrounding amino acids 307-330 of human USP1 is required for Cdh1 dependent degradation of USP1 (XREF_FIG).
21768287
CDH1 increases the amount of USP1.
| 1
CDH1 increases the amount of USP1. 1 / 1
| 1
reach
Although the depletion of Cdh1 increased USP1 expression, the levels of ubiquitinated USP1 were significantly reduced, suggesting that the formation of K11 linkage on USP1 was highly dependent on the function of Cdh1.
28604711
CDH1 activates USP1.
| 1
CDH1 activates USP1. 1 / 1
| 1
reach
In agreement with that, the depletion of Cdh1 markedly prolonged the retention of USP1 at DNA damage sites (XREF_FIG and XREF_SUPPLEMENTARY).
28604711
ALKBH5 affects USP1
| 1 2
ALKBH5 increases the amount of USP1.
| 1
ALKBH5 increases the amount of USP1. 1 / 1
| 1
reach
Mechanistically, ALKBH5 enhanced USP1 expression by reducing m6A level and mRNA stability in USP1 mRNA transcript.
34169564
ALKBH5 decreases the amount of USP1.
| 1
ALKBH5 decreases the amount of USP1. 1 / 1
| 1
reach
Downregulation of ALKBH5 reduced the levels of USP1 and Aurora B, facilitated CEM-C1 cell sensitivity to Dex, apoptosis, and GR expression, suppressed cell invasion.
34169564
ALKBH5 activates USP1.
| 1
ALKBH5 activates USP1. 1 / 1
| 1
eidos
Mechanistically , ALKBH5 enhanced USP1 expression by reducing m6A level and mRNA stability in USP1 mRNA transcript .
34169564
Pirinixic acid affects USP1
2 |
Pirinixic acid increases the amount of USP1. 2 / 2
2 |
ctd
No evidence text available
18301758
ctd
No evidence text available
21318169
Hsa-miR-7703 affects USP1
2 |
Hsa-miR-7703 decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23313552
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-766-3p affects USP1
2 |
Hsa-miR-766-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23824327
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-6776-5p affects USP1
2 |
Hsa-miR-6776-5p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23824327
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-6742-3p affects USP1
2 |
Hsa-miR-6742-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23313552
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6720-5p affects USP1
2 |
Hsa-miR-6720-5p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23313552
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-661 affects USP1
2 |
Hsa-miR-661 decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23313552
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6512-3p affects USP1
2 |
Hsa-miR-6512-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23824327
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-625-3p affects USP1
2 |
Hsa-miR-625-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
21572407
biopax:mirtarbase
No evidence text available
22012620
Hsa-miR-5683 affects USP1
2 |
Hsa-miR-5683 decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
21572407
biopax:mirtarbase
No evidence text available
22012620
Hsa-miR-542-3p affects USP1
2 |
Hsa-miR-542-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23824327
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-517c-3p affects USP1
2 |
Hsa-miR-517c-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-517b-3p affects USP1
2 |
Hsa-miR-517b-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-517a-3p affects USP1
2 |
Hsa-miR-517a-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-508-5p affects USP1
2 |
Hsa-miR-508-5p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23824327
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-4793-3p affects USP1
2 |
Hsa-miR-4793-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23313552
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-4536-3p affects USP1
2 |
Hsa-miR-4536-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-4517 affects USP1
2 |
Hsa-miR-4517 decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-4424 affects USP1
2 |
Hsa-miR-4424 decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-375 affects USP1
2 |
Hsa-miR-375 decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
20215506
biopax:mirtarbase
No evidence text available
15806104
Hsa-miR-298 affects USP1
2 |
Hsa-miR-298 decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-1185-2-3p affects USP1
2 |
Hsa-miR-1185-2-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
21572407
biopax:mirtarbase
No evidence text available
22012620
Hsa-miR-1185-1-3p affects USP1
2 |
Hsa-miR-1185-1-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Hsa-let-7f-2-3p affects USP1
2 |
Hsa-let-7f-2-3p decreases the amount of USP1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
21572407
Estrogen affects USP1
| 2
Estrogen activates USP1. 2 / 2
| 2
reach
This antagonistic effect of progesterone on estrogen induced USP-1 biosynthesis was also evident by the decreased staining intensity of USP-1 in uterine epithelial cells, as revealed by the immunohistochemical method.
3345728
reach
In the present communication, the effects of progesterone and antiprogesterone (RU 38486) on estrogen stimulated USP-1 biosynthesis were investigated.
3345728
Dibutyl phthalate affects USP1
2 |
Dibutyl phthalate decreases the amount of USP1. 2 / 2
2 |
ctd
No evidence text available
17361019
ctd
No evidence text available
21266533
Cyclosporin A affects USP1
2 |
Cyclosporin A increases the amount of USP1. 2 / 2
2 |
ctd
No evidence text available
27989131
ctd
No evidence text available
20106945
reach
ErGPCR-2 knockdown repressed 20E induced USP1 and CDK10 phosphorylation (XREF_FIG), which are essential for the formation of EcRB1 and USP1 transcription complex to initiate gene transcription in 20E signaling XREF_BIBR XREF_BIBR.
25728569
reach
20E, via GPCRs, induces rapid increase in cellular calcium and phosphorylation of transcription complex proteins USP1 and CDK10 to activate gene transcription XREF_BIBR.
25728569
USP1 affects localization
| 2
USP1 activates localization. 2 / 2
| 2
reach
Here we focused on the role of HubP in the regulation of flagellar number in V. alginolyticus Deletion of hubP increased the flagellar number and completely disrupted the polar localization of FlhG.
27573015
reach
These results, therefore, identify three USP1 amino acid motifs, having different degrees of nuclear import activity, that might contribute to the nuclear localization of this protein.
22701671
USP1 affects enzalutamide
| 2
USP1 inhibits enzalutamide. 2 / 2
| 2
reach
The supportive evidence is as follows : (i) USP1 knockdown decreased PC cell proliferation in vitro and tumorigenesis in vivo, and promoted the response to therapeutic agent enzalutamide; and (ii) inhibition of USP1 sensitized cancer cells to therapeutic agent enzalutamide, whereas this effect was blunted by overexpression of KDM4A.
32133742
reach
Furthermore, we found that USP1 knockdown reduced tumorigenesis and promoted PC cell response to therapeutic agent enzalutamide in a KDM4A dependent manner.
32133742
USP1 affects cisplatin
| 2
USP1 inhibits cisplatin. 2 / 2
| 2
reach
This view has gained recent support with the finding that USP1 inhibition may contribute to revert cisplatin resistance in an in vitro model of non small cell lung cancer (NSCLC).
23937906
reach
These findings are consistent with those of Chen et al. [XREF_BIBR], and suggest that USP1 inhibition may contribute to revert cisplatin resistance in some preclinical models of NSCLC.
23937906
USP1 affects cell death
| 2
USP1 inhibits cell death. 2 / 2
| 2
reach
Here, we demonstrate that targeting USP1 with a small molecule, can promote ID1 degradation and cell death in multiple leukemic cell lines.
24130053
reach
More recently developed compounds SJB2-043 and SJB3-019A inhibited the salvaging of ID1, ID2, ID3, FANC1 and FANCD2 proteins by Usp1 from proteosomal degradation and as a result caused an increase in cell death and sensitisation to DNA damaging agents [XREF_BIBR].
25962961
USP1 affects SNAI1
| 1 1
USP1 activates SNAI1. 2 / 2
| 1 1
reach
Here, we report that the ubiquitin specific protease 1 (USP1) mediates ovarian cancer cell resistance to platinum, by regulating the stability of Snail, which, in turn, promotes tumor dissemination.
31086816
eidos
USP1 upregulated SNAIL expression through deubiquitination to increase CXCL1 expression .
33926817
USP1 affects FUS
| 2
USP1 inhibits FUS. 2 / 2
| 2
reach
Recently, the deubiquitinating (DUB) enzyme USP1 was shown to directly remove the monoUb from PCNA, leading to the suggestion that USP1 is required to suppress the error-prone activity of TLS [XREF_BIBR].
16789823
reach
Accordingly, deficiency of USP1 leads to elevation of PCNA-Ub levels and disrupts TLS regulation [XREF_BIBR].
27906959
USP1 affects DNA replication
| 2
reach
USP1 modulates DNA replication polymerase choice and repair by deubiquitinating PCNA.
23589330
reach
Usp1 modulates DNA replication, polymerase choice and DNA repair by PCNA and as a result Usp1 knock-out mice are genetically unstable and hypersensitive to DNA damage [XREF_BIBR], [XREF_BIBR].
25962961
reach
USP1, a protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage response of these substrates.
18082605
reach
Loss of Deubiquitinase USP1 Blocks Pancreatic beta-Cell Apoptosis by Inhibiting DNA Damage Response.
30227958
PPP1 affects USP1
| 2
PPP1 activates USP1. 2 / 2
| 2
reach
When USP1 and UAF1 complex was treated with PP1, a large decrease in its activity was observed.
23116119
reach
The DUB activity of USP1 and UAF1 complex treated with PP1 was measured.
23116119
MIR375 affects USP1
| 2
MIR375 inhibits USP1. 2 / 2
| 2
eidos
Further experiments revealed that up-regulated miR-375 expression led to USP1 down-regulation , and miR-375 overexpression suppressed PI3K / Akt signaling and inhibited NPC cell migration and invasion , but promoted NPC cell apoptosis .
34626803
eidos
The luciferase assay confirmed miR-375 binding to the USP1 3 ' - untranslated region ( UTR ) , while the transfection experiment confirmed miR-375 expression reduced USP1 expression .
34626803
HOXA9 affects USP1
2 |
Transcriptionally active HOXA9 decreases the amount of USP1. 2 / 2
2 |
bel
Figure 6. HOXA9 target genes that are expressed in CD34+ stem cells
14604967
bel
Figure 2 - Gene expression changes due to overexpression of HOXA9 in human hematopoietic cell lines ##BW##
14604967
CDK1 affects USP1
| 2
CDK1 activates USP1. 2 / 2
| 2
reach
Thus, cyclin dependent kinase 1 (CDK1)-mediated phosphorylation of S313 during M phase was shown to prolong the stability of USP1 presumably by preventing its degradation by the anaphase promoting complex and cyclosome [XREF_BIBR].
25744535
reach
To demonstrate that CDK1 also phosphorylates the full-length USP1, individually purified USP1 was treated with CDK1 and incuabled with UAF1 at a 1:1 molar ratio at 37 degreesC for 15 minutes.
23116119
1,4-dithiothreitol affects USP1
| 1 1
sparser
However, our initial study suggested that purified USP1 alone is not activated by DTT ( xref ).
23463011
reach
However, our initial study suggested that purified USP1 alone is not activated by DTT (XREF_TABLE).
23463011
Testosterone affects USP1
1 | 1
Testosterone decreases the amount of USP1.
1 |
Testosterone decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
21592394
Testosterone activates USP1.
| 1
Testosterone activates USP1. 1 / 1
| 1
reach
Testosterone, progesterone, and dexamethasone failed to induce synthesis and secretion of USP-1 as assessed by dot blot enzyme immunoassay, immunoprecipitation of [35S] methionine labeled ULF proteins, and immunohistochemical staining of uterine tissue.
3275533
Progesterone affects USP1
| 2
Progesterone inhibits USP1.
| 1
Progesterone inhibits USP1. 1 / 1
| 1
reach
By radioimmune precipitation assay using specific antibody against USP-1, it was shown that progesterone can reduce the USP-1 synthesis and secretion, which were prestimulated by estrogen.
3345728
Progesterone activates USP1.
| 1
Progesterone activates USP1. 1 / 1
| 1
reach
Testosterone, progesterone, and dexamethasone failed to induce synthesis and secretion of USP-1 as assessed by dot blot enzyme immunoassay, immunoprecipitation of [35S] methionine labeled ULF proteins, and immunohistochemical staining of uterine tissue.
3275533
Doxycycline affects USP1
| 2
Doxycycline inhibits USP1.
| 1
Doxycycline inhibits USP1. 1 / 1
| 1
reach
A doxycycline induced USP1 shRNA suppressed USP1 expression and reduced ID1 and ID2 in the xenografts.
21925315
Doxycycline decreases the amount of USP1.
| 1
Doxycycline decreases the amount of USP1. 1 / 1
| 1
reach
A doxycycline induced USP1 shRNA suppressed USP1 expression and reduced ID1 and ID2 in the xenografts.
21925315
Bisphenol A affects USP1
2 |
Bisphenol A increases the amount of USP1.
1 |
Bisphenol A increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
25181051
Bisphenol A decreases the amount of USP1.
1 |
Bisphenol A decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
29275510
USP1 affects ZRANB3
| 2
USP1 inhibits ZRANB3.
| 1
USP1 inhibits ZRANB3. 1 / 1
| 1
reach
Interestingly, USP1 siRNA depletion prevented the dissociation of ZRANB3 from DNA damage sites and led to the persistence of ZRANB3 stripes 30 min after microirradiation (XREF_FIG and XREF_SUPPLEMENTARY).
22704558
USP1 activates ZRANB3.
| 1
USP1 activates ZRANB3. 1 / 1
| 1
reach
The spontaneous ZRANB3 foci induced by USP1 depletion co-localized also with WRNIP1 and RAD18 (XREF_FIG).
22704558
USP1 affects TAZ
| 2
USP1 increases the amount of TAZ.
| 1
USP1 increases the amount of TAZ. 1 / 1
| 1
reach
Conversely, loss of function of USP1 reduces TAZ protein levels through increased poly-ubiquitination, causing a decrease in cell proliferation and migration of breast cancer cells.
33114077
USP1 activates TAZ.
| 1
USP1 bound to TAZ activates TAZ. 1 / 1
| 1
reach
We demonstrated that USP1 interacts with TAZ and increases TAZ protein stability.
33114077
USP1 affects ESR1
| 2
USP1 inhibits ESR1.
| 1
USP1 inhibits ESR1. 1 / 1
| 1
reach
USP1 depletion inhibited breast cancer cell progression and ERalpha signaling activity.
33123289
USP1 activates ESR1.
| 1
USP1 activates ESR1. 1 / 1
| 1
reach
The deubiquitinating enzyme USP1 modulates ERalpha and modulates breast cancer progression.
33123289
USP1 affects BGLAP
| 2
USP1 increases the amount of BGLAP.
| 1
USP1 increases the amount of BGLAP. 1 / 1
| 1
reach
USP1 knockdown also reduced 143B tumor growth, promoted OSTEONECTIN, RUNX2, SPP1 and OSTEOPONTIN, OSTERIX, and BGLAP and OSTEOCALCIN expression, and enhanced ALP activity.
21925315
USP1 decreases the amount of BGLAP.
| 1
USP1 decreases the amount of BGLAP. 1 / 1
| 1
reach
USP1 knockdown also reduced 143B tumor growth, promoted OSTEONECTIN, RUNX2, SPP1 and OSTEOPONTIN, OSTERIX, and BGLAP and OSTEOCALCIN expression, and enhanced ALP activity.
21925315
TCF4 affects USP1
| 2
TCF4 increases the amount of USP1.
| 1
TCF4 increases the amount of USP1. 1 / 1
| 1
reach
beta-catenin and TCF4 activated transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly.
30425057
TCF4 deubiquitinates USP1.
| 1
TCF4 leads to the deubiquitination of USP1. 1 / 1
| 1
reach
beta-catenin and TCF4 activated transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly.
30425057
USP1 is modified
| 1 1
USP1 is produced.
| 1
USP1 is produced. 1 / 1
| 1
reach
Knockdown of ErGPCR repressed the binding of EcRB1 to EcRE thus blocked 20E induced expression of EcRB1, USP1, HHR3, BrZ2, and E75B in the cell line and larvae, which resulted in blocking the 20E genomic pathway, thereby inhibiting metamorphosis.
24507557
USP1 is degraded.
| 1
USP1 is degraded. 1 / 1
| 1
trips
These data suggest that calpain stabilizes USP1 by activating Cdk5, which in turn inhibits cdh1 and, consequently, USP1 degradation.
23589330
HNRNPD affects USP1
| 2
HNRNPD inhibits USP1.
| 1
HNRNPD inhibits USP1. 1 / 1
| 1
reach
MAT1A mRNA was previously stabilized by knockdown of AUF1, whereas transient knockdown of AUF1 by small interfering RNA (siRNA) transfection induces destabilization of APP, TOP2A, and USP1 mRNAs.
34729253
HNRNPD activates USP1.
| 1
HNRNPD activates USP1. 1 / 1
| 1
reach
26 December 2021 AUF1 by small interfering RNA (siRNA) transfection induces destabilization of APP, TOP2A, and USP1 mRNAs.
34729253
CTNNB1 affects USP1
| 2
CTNNB1 increases the amount of USP1.
| 1
CTNNB1 increases the amount of USP1. 1 / 1
| 1
reach
Beta-catenin and TCF4 activated transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly.
30425057
CTNNB1 deubiquitinates USP1.
| 1
CTNNB1 leads to the deubiquitination of USP1. 1 / 1
| 1
reach
Beta-catenin and TCF4 activated transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly.
30425057
CDKN1A affects USP1
| 2
CDKN1A decreases the amount of USP1.
| 1
CDKN1A decreases the amount of USP1. 1 / 1
| 1
reach
Secondly, USP1 expression is repressed by p21 upon exposure to DNA damaging agents.
22744751
CDKN1A activates USP1.
| 1
CDKN1A activates USP1. 1 / 1
| 1
reach
Significantly, CDKN1A siRNAs restored S phase entry in USP1 deficient U2-OS cells, indicating that p21 is essential for the cell-cycle arrest induced by USP1 knockdown.If ID degradation in the absence[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
21925315
Topotecan affects USP1
1 |
Topotecan decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
25729387
Thimerosal affects USP1
1 |
Thimerosal decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
27188386
Rottlerin affects USP1
| 1
Rottlerin inhibits USP1. 1 / 1
| 1
reach
In contrast, rottlerin was an irreversible inhibitor of USP1 and UAF1 with only 18% enzymatic activity recovered following the same incubation-dilution protocol.
22118673
Resveratrol affects USP1
1 |
Resveratrol increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
19167446
reach
In contrast to the irreversible destruction of USP1 triggered by UV exposure, reactive oxigen species (ROS) have recently been shown to induce a reversible inactivation of USP1 and also of other cysteine protease DUBs [XREF_BIBR - XREF_BIBR].
23937906
Piroxicam affects USP1
1 |
Piroxicam decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
21858171
Phorbol 13-acetate 12-myristate increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
25613284
Phlorizin affects USP1
1 |
Phlorizin increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
22538082
Phenobarbital affects USP1
1 |
Phenobarbital decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
23091169
Peptidase affects USP1
| 1
Peptidase deubiquitinates USP1. 1 / 1
| 1
reach
Finally, the modified ID 2 complex is deubiquitinated by the ubiquitin specific peptidase 1 (USP1) [46] and its activating partner UAF1 [47].
26512453
Oxaliplatin affects USP1
1 |
Oxaliplatin decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
25729387
Nitric oxide affects USP1
1 |
Nitric oxide increases the amount of USP1. 1 / 1
1 |
bel
Nitric oxide (NO*) can stabilize mRNA by activating p38 mitogen-activated protein kinase (MAPK). Here, transcript stabilization by NO* was investigated in human THP-1 cells using microarrays. After LPS pre-stimulation, cells were treated with actinomycin D and then exposed to NO* without or with the p38 MAPK inhibitor SB202190 (SB). The decay of 220 mRNAs was affected; most were stabilized by NO*. Unexpectedly, SB often enhanced rather than antagonized transcript stability. NO* activated p38 MAPK and Erk1/2; SB blocked p38 MAPK, but further activated Erk1/2. RT-PCR confirmed that NO* and SB could additively stabilize certain mRNA transcripts, an effect abolished by Erk1/2 inhibition. In affected genes, these responses were associated with CU-rich elements (CURE) in 3'-untranslated regions (3'-UTR). NO* stabilized the mRNA of a CURE-containing reporter gene, while repressing translation. Dominant-negative Mek1, an Erk1/2 inhibitor, abolished this effect. NO* similarly stabilized, but blocked translation of MAP3K7IP2, a natural CURE-containing gene. NO* increased hnRNP translocation to the cytoplasm and binding to CURE. Over-expression of hnRNP K, like NO*, repressed translation of CURE-containing mRNA. These findings define a sequence-specific mechanism of NO*-triggered gene regulation that stabilizes mRNA, but represses translation.
16757573
Kojic acid affects USP1
1 |
Kojic acid decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
16595896
Kind affects USP1
| 1
Kind increases the amount of USP1. 1 / 1
| 1
reach
Sendai virus (SeV), a kind of ssRNA virus recognized by RIG-I, markedly induced UAF1 and USP1 expression in mouse primary peritoneal macrophages at the early stage of infection (XREF_FIG).
29138248
Jinfukang affects USP1
1 |
Jinfukang decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
27392435
Ionomycin affects USP1
1 |
Ionomycin increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
25613284
Hydroxyurea affects USP1
| 1
Hydroxyurea activates USP1. 1 / 1
| 1
reach
They also demonstrated that a form of USP1 protein that is mutated for deubiquitination activity is resistant to degradation, suggesting that proteolysis of full-length USP1 to generate the 75 kDa fra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
16630883
Hsa-miR-940 affects USP1
1 |
Hsa-miR-940 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-7641 affects USP1
1 |
Hsa-miR-7641 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-7160-5p affects USP1
1 |
Hsa-miR-7160-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-6893-5p affects USP1
1 |
Hsa-miR-6893-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-6858-3p affects USP1
1 |
Hsa-miR-6858-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6849-3p affects USP1
1 |
Hsa-miR-6849-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6821-3p affects USP1
1 |
Hsa-miR-6821-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6808-5p affects USP1
1 |
Hsa-miR-6808-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-6790-3p affects USP1
1 |
Hsa-miR-6790-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6736-5p affects USP1
1 |
Hsa-miR-6736-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-665 affects USP1
1 |
Hsa-miR-665 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-6516-5p affects USP1
1 |
Hsa-miR-6516-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-6499-3p affects USP1
1 |
Hsa-miR-6499-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-640 affects USP1
1 |
Hsa-miR-640 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6087 affects USP1
1 |
Hsa-miR-6087 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-575 affects USP1
1 |
Hsa-miR-575 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-558 affects USP1
1 |
Hsa-miR-558 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-4722-5p affects USP1
1 |
Hsa-miR-4722-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-4701-3p affects USP1
1 |
Hsa-miR-4701-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-4695-3p affects USP1
1 |
Hsa-miR-4695-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-4676-5p affects USP1
1 |
Hsa-miR-4676-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-4649-3p affects USP1
1 |
Hsa-miR-4649-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-455-3p affects USP1
1 |
Hsa-miR-455-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-4487 affects USP1
1 |
Hsa-miR-4487 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-4327 affects USP1
1 |
Hsa-miR-4327 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-378a-5p affects USP1
1 |
Hsa-miR-378a-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-3653-5p affects USP1
1 |
Hsa-miR-3653-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-3160-3p affects USP1
1 |
Hsa-miR-3160-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-25-5p affects USP1
1 |
Hsa-miR-25-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-215-5p affects USP1
1 |
Hsa-miR-215-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19074876
Hsa-miR-1976 affects USP1
1 |
Hsa-miR-1976 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-192-5p affects USP1
1 |
Hsa-miR-192-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19074876
Hsa-miR-1262 affects USP1
1 |
Hsa-miR-1262 decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-1247-3p affects USP1
1 |
Hsa-miR-1247-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-1226-3p affects USP1
1 |
Hsa-miR-1226-3p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-100-5p affects USP1
1 |
Hsa-miR-100-5p decreases the amount of USP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23622248
Hexadecanoic acid affects USP1
| 1
reach
USP1 inhibition by ML323 at two concentrations (5 and 10 muM), which proved to be non toxic at basal levels (data not shown), potently inhibited the induction of caspase-3 and PARP cleavage triggered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
30227958
Hexabromocyclododecane increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
29177809
Gold atom affects USP1
1 |
Gold atom decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
25523186
Glucose affects USP1
| 1
Glucose inhibits USP1. 1 / 1
| 1
reach
USP1 inhibition by ML323 at two concentrations (5 and 10 muM), which proved to be non toxic at basal levels (data not shown), potently inhibited the induction of caspase-3 and PARP cleavage triggered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
30227958
Gentamycin affects USP1
1 |
Gentamycin increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
22061828
Genotoxin affects USP1
| 1
Genotoxin inhibits USP1. 1 / 1
| 1
sparser
Genotoxin-induced inactivation of USP1 (a PCNA-directed De-Ubiquitinating enzyme, or DUB) may contribute to PCNA mono-ubiquitination in some instances.
19587541
FtsI affects USP1
| 1
FtsI activates USP1. 1 / 1
| 1
reach
Taken together, these results suggest that FtsI is necessary to target the SPOR domain and HubP at future division sites in V. cholerae.
28300142
Fenofibrate affects USP1
1 |
Fenofibrate increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
21318169
Endosulfan affects USP1
1 |
Endosulfan increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
29391264
Dicrotophos affects USP1
1 |
Dicrotophos decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
28302478
Dexamethasone affects USP1
| 1
Dexamethasone activates USP1. 1 / 1
| 1
reach
Testosterone, progesterone, and dexamethasone failed to induce synthesis and secretion of USP-1 as assessed by dot blot enzyme immunoassay, immunoprecipitation of [35S] methionine labeled ULF proteins, and immunohistochemical staining of uterine tissue.
3275533
Coumestrol affects USP1
1 |
Coumestrol increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
19167446
Copper(II) sulfate affects USP1
1 |
Copper(II) sulfate decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
19549813
Copper atom affects USP1
1 |
Copper atom increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
16629173
Cisplatin affects USP1
1 |
Cisplatin decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
27392435
Calcitriol affects USP1
1 |
Calcitriol decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
21592394
Benzo[a]pyrene diol epoxide I decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
20382639
All-trans-retinoic acid decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
16249480
Aflatoxin M1 affects USP1
1 |
Aflatoxin M1 decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
30928695
ZUP1 affects USP1
| 1
ZUP1 activates USP1. 1 / 1
| 1
reach
Structures of non-selective DUB inhibitors.Structures of USP1/UAF1 inhibitors.Structures of a representative Novartis USP2 inhibitor and the cathepsin K inhibitor dutacatib.Structures of early USP7 inhibitors from Hybrigenics.USP7 IC50 4.2 μM USP7 IC 50 8.0 μM USP7 IC 50 0.42 μM USP47 IC 50 4.3 μM USP47 IC 50 8.7 μM USP47 IC 50 1.Structures of USP7 inhibitors from Progenra.Structures of recent USP7 inhibitors.Structures of USP8 inhibitors from Hybrigenics.Structures of a USP8 binder and two inhibitors of non-DUB cysteine proteases which advanced to clinical trials.
26852935
ZEB1 affects USP1
1 |
ZEB1 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
Water Pollutants, Chemical decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
22899542
WDR20 affects USP1
| 1
WDR20 activates USP1. 1 / 1
| 1
reach
USP12 and USP46, but not USP1, can be independently activated by another WD40-repeat-containing protein, WDR20 (Burska et al., 2013; Dahlberg and Juo, 2014; Kee et al., 2010; McClurg et al., 2014) .
27373336
WD40 affects USP1
| 1
WD40 activates USP1. 1 / 1
| 1
reach
For example, GMP synthetase (GMPS) interacts and activates USP7 (Faesen et al., 2011; Sarkari et al., 2009; van der Knaap et al., 2005), whereas the WD40 repeat containing UAF1 (WDR48) activates USP1,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
22195557
Ubiquitin affects USP1
| 1
Ubiquitin inhibits USP1. 1 / 1
| 1
reach
The activity of the PI3K/Akt/FoxO pathway has been shown to be suppressed by the deubiquitinating enzyme ubiquitin-specific protease 1 (USP1) in muscle.
34572540
USP1 affects proteolysis
| 1
USP1 bound to WDR48 activates proteolysis. 1 / 1
| 1
reach
To further investigate whether USP1 and UAF1 complex could inhibit TBK1 protein degradation, a cycloheximide (CHX) chase experiment was performed.
29138248
eidos
Collectively , we showed that USP1 interacts with KDM4A and promotes its deubiquitination , ultimately leading to KDM4A stabilization , and inhibition of USP1 promotes the response of PC cells to therapeutic agent enzalutamide ( Figure7H ) .
32133742
USP1 activates polyinosinic:polycytidylic acid. 1 / 1
| 1
reach
In addition, UAF1 and USP1 overexpression both significantly enhanced LPS-, polyinosinic : polycytidylic acid [poly (I : C)]-, and SeV induced IFN-beta reporter gene activation (XREF_FIG), with no effects on NF-kappaB activation (XREF_FIG).
29138248
USP1 affects pevonedistat
| 1
USP1 activates pevonedistat. 1 / 1
| 1
reach
USP1, USP46, and WDR20 are candidate ubiquitylation targets (XREF_FIG), as they are either only detected or APSMs increase in the presence of MLN4924 and/or Btz.
24035498
USP1 affects methoprene
| 1
USP1 inhibits methoprene. 1 / 1
| 1
reach
Other transcription factors Ha-USP1 and Ha-Br-Z2 suppressed the action of methoprene in inducing Ha-GRIM-19 expression, but Ha-Br-Z2 introduced interaction between 20E and methoprene in upregulation of Ha-GRIM-19.
21184119
USP1 affects flhF
| 1
USP1 decreases the amount of flhF. 1 / 1
| 1
reach
The amount of FlhF at the cell pole was not increased by the deletion of hubP (hyperflagellation) and was not reduced by the overproduction of flhG (nonflagellation).
32244780
USP1 bound to WDR48 activates epithelial to mesenchymal transition. 1 / 1
| 1
reach
In this study, we identified that the USP1 and WDR48 complex could effectively enhance TGF-beta-mediated EMT and migration of TNBC cells.
33461373
USP1 bound to WDR48 activates double-strand break repair. 1 / 1
| 1
reach
The USP1 and UAF1 complex promotes double-strand break repair through homologous recombination.
21482670
USP1 affects dioxygen
| 1
USP1 inhibits dioxygen. 1 / 1
| 1
reach
The double knockdown of either ITGB4 and PXN or USP1 and VDAC1 combination increases mitochondrial oxygen consumption rate, leading to increased ROS generation resulting ultimately in increased DNA damage.
32947124
USP1 inhibits cyclobutane-1,1-dicarboxylate(2-). 1 / 1
| 1
reach
Validation screening by using five specific shRNA and gene on four different EOC cell lines (i.e., MDAH, SKOV3, TOV112D, and OV-90), demonstrated that silencing of five genes, namely ATR, BCL2L1 (also known as Bcl-XL), SGK2, USP1, and SFPQ, were able to significantly increase CBDCA response, in at least 3/4 tested cell lines.
32332923
USP1 affects cell migration
| 1
USP1 activates cell migration. 1 / 1
| 1
reach
USP1 enhances the expression of a number of pro metastatic genes in breast cancer cells, promotes cell migration and invasion in vitro, and facilitates lung metastasis of breast cancer cells.
30531833
USP1 affects cell cycle
| 1
USP1 inhibits cell cycle. 1 / 1
| 1
reach
As reported in Figure XREF_FIG A, USP1 depleted U2OS cells re-enter the cell cycle more rapidly than USP1-proficient cells, suggesting that USP1 depletion could accelerate recovery from the G2 checkpoint.
21389083
USP1 affects USP46
| 1
USP1 activates USP46. 1 / 1
| 1
reach
The WD-repeat protein WDR48 (USP1 associated factor UAF-1) stimulates activity of ubiquitin specific proteases USP1, USP12, and USP46.
26388029
USP1 affects USP3
| 1
USP1 activates USP3. 1 / 1
| 1
reach
In addition, DUBs involved in DNA damage signaling are USP1 that targets PCNA (proliferating cell nuclear antigen) [76], FANCD2 and FANCI (the Fanconi anemia proteins) [93,94], and USP3 and USP16 that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
21763684
USP1 affects USP16
| 1
USP1 activates USP16. 1 / 1
| 1
reach
In addition, DUBs involved in DNA damage signaling are USP1 that targets PCNA (proliferating cell nuclear antigen) [76], FANCD2 and FANCI (the Fanconi anemia proteins) [93,94], and USP3 and USP16 that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
21763684
USP1 affects USP12
| 1
USP1 activates USP12. 1 / 1
| 1
reach
The WD-repeat protein WDR48 (USP1 associated factor UAF-1) stimulates activity of ubiquitin specific proteases USP1, USP12, and USP46.
26388029
USP1 affects USP
| 1
USP1 activates USP. 1 / 1
| 1
reach
Several structurally unrelated inhibitors of human USP1 were discovered in mM range but inhibited at least one other human USP with similar potencies (Chen et al., 2011) .
22520747
USP1 affects TP53
| 1
USP1 activates TP53. 1 / 1
| 1
reach
The tumor suppressor p53, a well-known inducer of CDKN1A, was not increased by USP1 knockdown, suggesting that increased p21 was p53 independent.p21 is a potent inhibitor of cell cycle progression (Po[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
21925315
USP1 affects Selenos
| 1
USP1 activates Selenos. 1 / 1
| 1
reach
Remarkably, USP1 depletion in senescence bypassing cells equally induces replication stress, perturbed S/G2 transition, and polyploidy, implying that USP1 deficiency creates a milieu conducive for gen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
27160904
USP1 affects SPARC
| 1
USP1 decreases the amount of SPARC. 1 / 1
| 1
reach
USP1 or ID knockdown also increased expression of osteoblastic RUNX2, OSTERIX, and OSTEONECTIN, and increased ALP activity.
21925315
USP1 affects SNAIL
| 1
USP1 increases the amount of SNAIL. 1 / 1
| 1
reach
USP1 upregulated SNAIL expression through deubiquitination to increase CXCL1 expression.
33926817
USP1 affects SIK2
| 1
USP1 inhibits SIK2. 1 / 1
| 1
reach
Silencing of USP1 was shown to target SIK2 to inhibit colony formation capacity and invasiveness of osteosarcoma cells by stimulating apoptosis [XREF_BIBR].
29774109
USP1 affects RUNX2
| 1
USP1 decreases the amount of RUNX2. 1 / 1
| 1
reach
USP1 or ID knockdown also increased expression of osteoblastic RUNX2, OSTERIX, and OSTEONECTIN, and increased ALP activity.
21925315
USP1 affects RIPK1
| 1
Modified USP1 increases the amount of RIPK1. 1 / 1
| 1
reach
In addition, UAF1 and USP1 overexpression both enhanced RIP1 protein expression, indicating that RIP1 may be another target of USP1 and UAF1, and that needs to be further investigated.
29138248
eidos
Taken together , these results demonstrate that USP1 promote B-ALL progression at least partially via the ID1 / AKT signaling pathway , and USP1 inhibitors might be promising therapeutic application for B-ALL .
33390793
USP1 affects PadR
| 1
USP1 inhibits PadR. 1 / 1
| 1
reach
PadR can not be inactivated directly by phenolic acid in E. coli recombinant cultures but is inactivated by Usp1 when the two proteins are coexpressed in E. coli.
19542339
USP1 affects PXN
| 1
USP1 increases the amount of PXN. 1 / 1
| 1
reach
ITGB4 and PXN Regulate USP1 Transcription Epigenetically.
32947124
USP1 affects PRRC2A
| 1
USP1 inhibits PRRC2A. 1 / 1
| 1
eidos
Other two previous studies have confirmed the USP1 depletion caused cells arrest in G2 / M phase 17 , 18 .
33390793
USP1 affects PODXL
| 1
USP1 activates PODXL. 1 / 1
| 1
eidos
In addition , inhibition of USP1 decreased PC proliferation and promoted response to therapeutic agent enzalutamide in a KDM4A-dependent manner .
32133742
USP1 affects PKC
| 1
USP1 increases the amount of PKC. 1 / 1
| 1
reach
Knockdown of USP1 also did not suppress the level of HaCal mRNA but suppressed the level of Met1 and increased the levels of PKC and JHi in the JH signaling (lane K compared to I).
21625546
USP1 affects PI3K
| 1
USP1 activates PI3K. 1 / 1
| 1
reach
In addition, USP1 overexpression activated phosphoinositide 3-kinase (PI3K) signaling, whereas a selective PI3K inhibitor (S2739) could reverse the effects of USP1 on NPC cells in vitro.
34626803
USP1 affects PHLPP1
| 1
USP1 inhibits PHLPP1. 1 / 1
| 1
reach
Both USP1 and PHLPP1 are low expressed in lung cancer cells and tissues and silencing of USP1 by RNA interference significantly decreased the half-life of PHLPP1, which in turn amplified Akt1 phosphorylation.
22426999
USP1 affects PCBD1
| 1
USP1 activates PCBD1. 1 / 1
| 1
reach
In summary, 20E up-regulates the transcription of Hippo via EcRB1, USP1, and HR3 to induce PCD, and Hippo has negative feedback effects on HR3 expression.
26272745
USP1 affects PARP1
| 1
USP1 activates PARP1. 1 / 1
| 1
reach
USP1 inhibition by ML323 at two concentrations (5 and 10 muM), which proved to be non toxic at basal levels (data not shown), potently inhibited the induction of caspase-3 and PARP cleavage triggered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
30227958
USP1 activates Neoplastic Stem Cells. 1 / 1
| 1
reach
Considering the action of the proteins ID, USP1 contributes to prevent differentiation mediated by bHLH and, consequently, keep CSC original characteristics.
28302046
USP1 affects NKX3-1
| 1
USP1 activates NKX3-1. 1 / 1
| 1
reach
We found that R1881 induced a significant increase in NKX3.1 (a positive control) transcript in RV1 cells, but it failed to induce the c-Myc transcript, and USP1 knockdown reduced the c-Myc or NKX3.1 transcript similarly, with or without R1881.
32133742
USP1 affects NGR1
| 1
USP1 increases the amount of NGR1. 1 / 1
| 1
reach
The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression.
33479772
USP1 affects NFkappaB
| 1
USP1 activates NFkappaB. 1 / 1
| 1
reach
In addition, UAF1 and USP1 both greatly enhanced TBK1 induced IRF3, ISRE, and NF-kappaB activation (XREF_FIG).
29138248
USP1 affects NES
| 1
USP1 activates NES. 1 / 1
| 1
reach
As shown in XREF_FIG, the three USP1 motifs tested were able to induce the nuclear relocation of NES-GFP, although to a different extent.
22701671
USP1 affects MON2
| 1
USP1 increases the amount of MON2. 1 / 1
| 1
reach
USP1, USP12, and UAF1 were produced using Sf9 and Sf21 insect cell expression.
22195557
USP1 affects MCL1
| 1
USP1 activates MCL1. 1 / 1
| 1
reach
In cultured CRC cells, knockdown of USP1 induced growth arrest at G 2 / M of cell cycle and reduced the expression of anti-apoptotic proteins Bcl-2 and Mcl-1.
31921663
USP1 affects LUM
| 1
USP1 activates LUM. 1 / 1
| 1
reach
Taken together, these data demonstrate that PD regulation of USP1 reduces permeability and maintains barrier integrity in VEGF-induced endothelial cells.Regulation of endothelial barrier function is critical for vascular function and integrity (Lum and Malik, 1994; Surapisitchat and Beavo, 2011).
34149436
USP1 affects LRIF1
| 1
USP1 inhibits LRIF1. 1 / 1
| 1
reach
In contrast to the overexpression, the depletion of USP1 increased the number of BRCA1 foci but decreased the number of RIF1 foci in S/G2 cells (XREF_FIG, XREF_SUPPLEMENTARY).
28604711
USP1 affects K562 Cells
| 1
USP1 activates K562 Cells. 1 / 1
| 1
eidos
Inhibition of USP1 , a new partner of Bcr-Abl , results in decrease of Bcr-Abl level in K562 cells .
32602291
USP1 affects ITGB4
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USP1 increases the amount of ITGB4. 1 / 1
| 1
reach
ITGB4 and PXN Regulate USP1 Transcription Epigenetically.
32947124
USP1 affects ISPH
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USP1 inhibits ISPH. 1 / 1
| 1
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More importantly, the depletion of USP1 restored the reduction in HDR efficiency caused by compromised Cdh1 function, reinforcing the notion that APC Cdh1 antagonizes USP1.
28604711
USP1 affects IRF3
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USP1 activates IRF3. 1 / 1
| 1
reach
In addition, UAF1 and USP1 both greatly enhanced TBK1 induced IRF3, ISRE, and NF-kappaB activation (XREF_FIG).
29138248
USP1 affects ID3
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USP1 activates ID3. 1 / 1
| 1
reach
USP1 knockdown specificity was confirmed with shRNA resistant USP1, which restored ID1, ID2, and ID3 to basal levels.
21925315
USP1 affects HR3
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USP1 inhibits HR3. 1 / 1
| 1
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Knockdown of USP1 partially suppressed the induction of EcR-B1 and HR3 but did not suppress the mRNA level of HaCal induced by 20E (lane D compared to B).
21625546
USP1 affects Glu-Ser
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USP1 activates Glu-Ser. 1 / 1
| 1
reach
Usp1 gene targeted C57BL/6 ES cells were from the Knockout Mouse Project Repository (Davis, CA).
21925315
USP1 affects FBXW11
| 1
USP1 activates FBXW11. 1 / 1
| 1
reach
USP1 knockdown similarly reduced proliferation in HOS, SAOS, and SJSA, but not MG-63 osteosarcoma cells.
21925315
USP1 affects E3_Ub_ligase
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USP1 inhibits E3_Ub_ligase. 1 / 1
| 1
reach
The FANCD2 and FANCI complex may change their conformation upon binding with DNA, which is more open to ubiquitination by the core complex E3 ligase that is antagonized by USP1.
28552166
USP1 affects Death
| 1
USP1 activates Death. 1 / 1
| 1
reach
Genetic silencing and pharmacological suppression of USP1 blocked beta-cell death in several experimental models of diabetes invitro and exvivo without compromising insulin content and secretion and without impairing beta-cell maturation and identity genes in human islets.
30227958
reach
These results suggest that USP1 is an inhibitor of DSB induced chromatin ubiquitination in S/G2 cells.
28604711
USP1 affects DDM1
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USP1 activates DDM1. 1 / 1
| 1
reach
HubP leads Chr1 segregation.
28300142
USP1 affects Carcinogenesis
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USP1 activates Carcinogenesis. 1 / 1
| 1
eidos
Furthermore , we found that USP1 knockdown reduced tumorigenesis and promoted PC cell response to therapeutic agent enzalutamide in a KDM4A-dependent manner .
32133742
USP1 affects CXCL1
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USP1 increases the amount of CXCL1. 1 / 1
| 1
reach
USP1 upregulated SNAIL expression through deubiquitination to increase CXCL1 expression.
33926817
USP1 affects CDT1
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USP1 decreases the amount of CDT1. 1 / 1
| 1
reach
It is important to note that USP1 depletion neither reduced the steady-state level of another known DDB1 target, chromatin licensing and DNA replication factor 1 (CDT1), nor enhanced its DNA damage induced degradation, suggesting that the DDB1 and CUL4A machinery is not simply overactive in USP1 depleted cells.
21389083
USP1 affects CD8
| 1
USP1 decreases the amount of CD8. 1 / 1
| 1
reach
Usp1 deficiency resulted in a gradual loss of memory CD8 + T cells over time and reduced Id2 protein levels and proliferation of effector CD8 + T cell following reinfection.
34380645
USP1 affects CASP3
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USP1 activates CASP3. 1 / 1
| 1
reach
USP1 inhibition by ML323 at two concentrations (5 and 10 muM), which proved to be non toxic at basal levels (data not shown), potently inhibited the induction of caspase-3 and PARP cleavage triggered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
30227958
USP1 affects CASC3
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USP1 activates CASC3. 1 / 1
| 1
reach
USP1, USP46, and WDR20 are candidate ubiquitylation targets (XREF_FIG), as they are either only detected or APSMs increase in the presence of MLN4924 and/or Btz.
24035498
USP1 affects CA9
| 1
USP1 activates CA9. 1 / 1
| 1
reach
T. Huang and colleagues have previously reported that MN accumulation induced by USP1 depletion depends on Pol kappa.
27740454
USP1 affects BCL2
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USP1 activates BCL2. 1 / 1
| 1
reach
In cultured CRC cells, knockdown of USP1 induced growth arrest at G 2 / M of cell cycle and reduced the expression of anti-apoptotic proteins Bcl-2 and Mcl-1.
31921663
USP1 affects AR
| 1
USP1 inhibits AR. 1 / 1
| 1
reach
Downregulation of either USP1, KDM4A, and/or AR decreased binding of AR to the c-Myc enhancer.
32133742
USP1 affects ALKBH5
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USP1 inhibits ALKBH5. 1 / 1
| 1
reach
However, overexpression of USP1 reversed all the effects of ALKBH5 on CEM-C1 cells.
34169564
USP1 affects AKT
| 1
USP1 increases the amount of phosphorylated AKT. 1 / 1
| 1
reach
Finally, we found that inhibition of USP1 downregulated the expression of ID1 and p-AKT, and upregulated ID1 expression could reverse the suppressive effects of USP1 inhibitor in B-ALL cells.
33390793
UNC119 affects USP1
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UNC119 activates USP1. 1 / 1
| 1
reach
The observations that the translation of the USP1 mRNA driven by the unfolded RG4 (7dG modified) was insensitive to stabilizing ligands but much more responsive to hnRNP H/F loss compared to the USP1 RG4 WT suggest that the dynamic equilibrium between RG4s and linear G rich sequences in cellulo results in low binding of hnRNP H/F to RG4s but, when preventing RG4 from folding, hnRNP H/F strongly bind the G rich RNA to potentiate translation.
32461552
Tretinoin affects USP1
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Tretinoin decreases the amount of USP1. 1 / 1
1 |
bel
TABLE 3. Downregulated Gene Expression (45 Genes) in HCjE Cells Treated with RA for 24 and 48 Hours
16249480
TSC1 affects USP1
| 1
TSC1 inhibits USP1. 1 / 1
| 1
reach
Surprisingly, USP1 limits TSC1 levels to sustain mTOR mediated basal protein synthesis rates and maintain its own protein levels.
32133736
TFCP2 affects USP1
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TFCP2 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
TCF3 affects USP1
1 |
TCF3 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
TCF12 affects USP1
1 |
TCF12 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
SPRTN affects USP1
| 1
SPRTN inhibits USP1. 1 / 1
| 1
reach
Spartan inhibits the USP1 dependent deubiquitylation of ubiquitin conjugated PCNA.
22987070
SP1 affects USP1
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SP1 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
RPE affects USP1
| 1
RPE activates USP1. 1 / 1
| 1
reach
Incubation of the RPE on AGE-BM induced a 2.1- and 4.5-fold increase in protein disulphide isomerase (PDI) and ubiquitin carboxyl-terminal hydrolase 1 (UCH L1) densitometry respectively.
22081232
eidos
Afterwards , siRNA and small molecular inhibitor were used to downregulate USP1 expression , aiming to further investigate the functional significance of USP1 in B-ALL-derived cell lines .
33390793
RIPK1 affects USP1
| 1
RIPK1 activates USP1. 1 / 1
| 1
reach
In addition, UAF1 and USP1 overexpression both enhanced RIP1 protein expression, indicating that RIP1 may be another target of USP1 and UAF1, and that needs to be further investigated.
29138248
REPIN1 affects USP1
1 |
REPIN1 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
RAS affects USP1
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RAS inhibits USP1. 1 / 1
| 1
reach
We confirmed that oncogenic RAS senescent cells have reduced USP1 transcript and protein levels compared to pre-senescent cells.
27160904
Phosphatase affects USP1
| 1
Phosphatase activates USP1. 1 / 1
| 1
reach
In a control experiment, the USP1 and UAF1 complex treated with phosphatase buffer did not result in an appreciable decrease in the activity of USP1 and UAF1 complex.
23116119
PYR3 affects USP1
| 1
PYR3 inhibits USP1. 1 / 1
| 1
reach
The 20E induced upregulation of EcRB1, BrZ2, HHR3, and USP1 was suppressed by FL and Pyr3.
24507557
PKC affects USP1
| 1
PKC decreases the amount of USP1. 1 / 1
| 1
reach
Knockdown of PKC suppressed the transcript levels of USP1, Br-Z2, and HaCal induced by 20E (lane F compared to B).
21625546
PDGF affects USP1
| 1
PDGF activates USP1. 1 / 1
| 1
reach
USP1 is up-regulated by PDGF via E2F.
28122577
PCBP1 affects USP1
1 |
PCBP1 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
PARP1 affects USP1
| 1
PARP1 inhibits USP1. 1 / 1
| 1
reach
USP1 inhibition by ML323 at two concentrations (5 and 10 muM), which proved to be non toxic at basal levels (data not shown), potently inhibited the induction of caspase-3 and PARP cleavage triggered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
30227958
Nutlin 3 affects USP1
1 |
Nutlin 3 decreases the amount of USP1. 1 / 1
1 |
bel
Supplemental Table I. Probe sets altered by nutlin-3a treatment. From results: Of ?40,000 human transcripts represented on the chip, 143 genes (166 probe sets) were found differentially expressed in HCT116 cells treated with nutlin-3a (Fig. 1D and Table 1, which is published as supporting information on the PNAS web site). The list included multiple genes previously shown to be affected by p53 activation (19?21), including 32 transcripts reported as directly regulated by p53. Changes in the expression of many genes may reflect the altered cell-cycle distribution in cells that arrest predominantly in G1 and G2 phases as a result of p53 activation (12). With the exception of a few genes that were marginally down-regulated in HCT116 cells, the inactive enantiomer did not significantly change the gene expression profile of both cell lines. Taken together, the data in Fig. 1 indicate that nutlin-3a is a highly selective MDM2 antagonist and p53 inducer. *Differential expression was determined as 3-fold altered in HCT116 treated with nutlin-3a vs. vehicle and P < 0.05, and no change (<1.5-fold change) in the H1299 cells or HCT116 treated with nutlin-3b. **Expression vaules are the average of three replicates of Affymetrix MAS5 signal intensities scaled to the median of the experiment. P value calculations are a simple t test P value of the null hypothesis of no difference between nutlin-3a treated samples vs. DMSO-treated samples.
16443686
Niclosamide affects USP1
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Niclosamide decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
31398420
NFkappaB affects USP1
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NFkappaB activates USP1. 1 / 1
| 1
sparser
In addition, UAF1 and USP1 both greatly enhanced TBK1-induced IRF3, ISRE, and NF-κB activation ( xref ).
29138248
MYC affects USP1
| 1
MYC activates USP1. 1 / 1
| 1
reach
To examine whether expression of c-Myc could rescue the effect of USP1 and KDM4A depletion on proliferation and survival of PC cells, we undertook MTT assay.
32133742
KDM4A affects USP1
| 1
KDM4A increases the amount of USP1. 1 / 1
| 1
sparser
These results suggest that AR ligand is not required for USP1‐ KDM4A axis‐dependent transcription of c‐Myc.
32133742
K 7174 affects USP1
1 |
K 7174 increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
24086573
IRF3 affects USP1
| 1
IRF3 activates USP1. 1 / 1
| 1
sparser
In addition, UAF1 and USP1 both greatly enhanced TBK1-induced IRF3, ISRE, and NF-κB activation ( xref ).
29138248
IFNB1 affects USP1
| 1
IFNB1 decreases the amount of USP1. 1 / 1
| 1
reach
Interestingly, IFN-beta stimulation dramatically decreased UAF1 and USP1 expression (XREF_FIG).
29138248
HPS6 affects USP1
| 1
HPS6 activates USP1. 1 / 1
| 1
reach
Although RU 38486 itself did not manifest any effect on estrogen stimulated USP-1 biosynthesis, it completely inhibited the progesterone induced decrease in synthesis and secretion.
3345728
Glioblastoma affects USP1
| 1
Glioblastoma activates USP1. 1 / 1
| 1
eidos
USP1 was chosen for further investigation also because its increased expression in GBM has been associated to resistance to treatments55 , providing a rationale for USP1 inhibition as a potential therapeutic approach against GBM .
32461552
GRK2 affects USP1
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GRK2 inhibits USP1. 1 / 1
| 1
reach
Results showed that knockdown of GRK2 also increased 20E induced genes (EcR-B1, USP1, HR3, and BrZ7) expression levels (XREF_FIG).
27412951
Enterolactone affects USP1
1 |
Enterolactone increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
19167446
ELG1 affects USP1
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ELG1 increases the amount of USP1. 1 / 1
| 1
reach
One possibility is that ELG1 modulates the expression or stability of USP1.
21640107
EGR1 affects USP1
1 |
EGR1 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
reach
In addition, USP1 overexpression activated phosphoinositide 3-kinase (PI3K) signaling, whereas a selective PI3K inhibitor (S2739) could reverse the effects of USP1 on NPC cells in vitro.
34626803
E6 affects USP1
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E6 inhibits USP1. 1 / 1
| 1
reach
Finally, E6 could suppress USP1 de-ubiquitinating activity, and led to persistent activation of ATR/CHK-1/pS565 FancI signaling XREF_BIBR - XREF_BIBR.
33299640
E3_Ub_ligase affects USP1
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E3_Ub_ligase activates USP1. 1 / 1
| 1
reach
USP1 is targeted for proteasomal degradation by the multi-subunit E3 ligase, APC/C Cdh1 in a cell cycle dependent manner [XREF_BIBR], so perhaps the decrease in USP1 is a consequence of the ability of PEITC to cause cell cycle arrest [XREF_BIBR, XREF_BIBR].
28881649
E2F1 affects USP1
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E2F1 decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
E2 affects USP1
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E2 activates USP1. 1 / 1
| 1
reach
Peptide-N-glycosidase treatment of USP-1 induced by E2 or tamoxifen removed asparagine linked carbohydrate chains and resulted in the appearance of polypeptides with apparent mol wt of 91K and 105K, respectively.
3383775
DHX36 affects USP1
| 1
DHX36 activates USP1. 1 / 1
| 1
reach
In agreement with polysomal analysis of USP1 mRNA translation regulation by hnRNP H/F or DHX36, silencing of either of these factors or treatment with cPDS reduced USP1 protein expression, providing further support for a RG4 dependent translational mechanism in which both hnRNP H/F and DHX36 cooperate to activate USP1 protein synthesis.
32461552
DDB1 affects USP1
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DDB1 activates USP1. 1 / 1
| 1
reach
USP1 limits DDB1 dependent degradation of CHK1.
21389083
CPG-oligonucleotide increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
21878529
CFH affects USP1
| 1
CFH activates USP1. 1 / 1
| 1
reach
In agreement with polysomal analysis of USP1 mRNA translation regulation by hnRNP H/F or DHX36, silencing of either of these factors or treatment with cPDS reduced USP1 protein expression, providing further support for a RG4 dependent translational mechanism in which both hnRNP H/F and DHX36 cooperate to activate USP1 protein synthesis.
32461552
CDK5 affects USP1
| 1
CDK5 activates USP1. 1 / 1
| 1
reach
These data suggest that calpain stabilizes USP1 by activating Cdk5, which in turn inhibits cdh1 and, consequently, USP1 degradation.
23589330
CASP3 affects USP1
| 1
CASP3 inhibits USP1. 1 / 1
| 1
reach
USP1 inhibition by ML323 at two concentrations (5 and 10 muM), which proved to be non toxic at basal levels (data not shown), potently inhibited the induction of caspase-3 and PARP cleavage triggered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
30227958
Aroclor 1254 affects USP1
1 |
Aroclor 1254 decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
23650126
Antigens, Polyomavirus Transforming increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
26680231
APC_C affects USP1
| 1
APC_C inhibits USP1. 1 / 1
| 1
reach
USP1 degradation directed by the cell cycle regulator APC/C (cdh1), which marks USP1 for destruction in the G1 phase, is upregulated in CAPNS1 depleted cells.
23589330
APC affects USP1
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APC inhibits USP1. 1 / 1
| 1
reach
It was recently shown that APC and CCdh1 triggers USP1 degradation specifically in G1 after UV irradiation.
23723248
AK2 affects USP1
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AK2 inhibits USP1. 1 / 1
| 1
reach
The results of semi-quantitative RT-PCR showed that knockdown of AK2 caused suppression of the molting hormone nuclear receptor EcRB1, transcription factors USP1 and Br, as well as protein kinase AKT genes.
23020757
AHR affects USP1
1 |
AHR decreases the amount of USP1. 1 / 1
1 |
biopax:msigdb
No evidence text available
2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
17942748
ctd
No evidence text available
24096037
(-)-demecolcine affects USP1
1 |
(-)-demecolcine decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
23649840
(+)-JQ1 compound affects USP1
1 |
(+)-JQ1 compound decreases the amount of USP1. 1 / 1
1 |
ctd
No evidence text available
24796395
ctd
No evidence text available
19114083