USP48 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 48
HGNC Gene Symbol
USP48
Identifiers
hgnc:18533 NCBIGene:84196 uniprot:Q86UV5
Orthologs
mgi:2158502 rgd:735213
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP48
Number of Papers
45 retrieved on 2022-05-22

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
ACOT7 acyl-CoA thioesterase 7 0.227 0.26 1.34 2.83e-06
PIK3R3 phosphoinositide-3-kinase regulatory subunit 3 0.21 -0.14 -0.85 3.13e-02
H1-5 H1.5 linker histone, cluster member 0.192 0.10 0.48 9.30e-02
KIAA0319L KIAA0319 like 0.188 0.06 0.22 4.09e-01
GALNT4 polypeptide N-acetylgalactosaminyltransferase 4 -0.181 Reactome (2)
CLCNKA chloride voltage-gated channel Ka 0.176
ZNF101 zinc finger protein 101 -0.174

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP48using 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

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP48 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
USP48 ubiquitin specific peptidase 48 -1.16e+00 1.91e-06 4.21e-02

Gene Set Enrichment Analysis

There were too few differentially expressed genes to run a meaningful GSEA.

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP48 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 lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP48 deubiquitinates TRAF2. 3 / 3
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Here we reveal USP48 as the first identified DUB to deubiquitinate and stabilize TRAF2 in epithelial cells.

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The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions

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USP48 (also known as USP31) interacted with and deubiquitinated TRAF2 in beas2B cells [71].
USP48 deubiquitinates H2AC19. 1 / 1
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Here we identify ubiquitin specific protease-48 (USP48) as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination site.
USP48 deubiquitinates GLI1. 1 / 1
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Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1
USP48 deubiquitinates H2AC8. 1 / 1
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USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A
USP48 leads to the deubiquitination of MDM2. 1 / 1
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In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels.
Modified USP48 leads to the deubiquitination of FANCD2. 1 / 1
| 1

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Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background.
Modified USP48 leads to the deubiquitination of FANCI. 1 / 1
| 1

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Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background.

Other Statements

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USP48 affects MDM2
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USP48 activates MDM2.
| 9
USP48 activates MDM2. 9 / 9
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Recently, USP48 has also been shown to promote the stability of Mdm2 that in turn results in enhanced degradation of p53 42, which has been associated to FA cell death 43.

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To determine whether the observed USP48 mediated Mdm2 upregulation might reflect increased stability on the protein level, we performed a cycloheximide (CHX) chase assay in U2OS cells transfected either with the Mdm2 construct alone or in combination with USP48.

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Interestingly, when we analyzed the pattern of Mdm2 ubiquitination in the presence of the deubiquitinase defective mutant USP48 C98S, we again observed that less ubiquitin was attached to Mdm2 via lysine 48 compared to other lysines, suggesting that the deubiquitinase activity of USP48 was not responsible for the previously observed difference and supporting our notion that USP48 did not target Mdm2 with its deubiquitinase activity.

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Moreover, these results also suggested that USP48 does not mediate Mdm2 stabilization through the deubiquitination of other Mdm2 regulators.

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We were surprised to find that USP48 caused Mdm2 stabilization that was not accompanied by a significant decrease in the overall levels of Mdm2 ubiquitination, which was unexpected (XREF_FIG).

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Nevertheless, we can not exclude the possibility that USP48 (and its deubiquitinase inactive mutants) are capable of recruiting another deubiquitinase responsible for trimming K48 linked ubiquitin, and future studies are necessary to determine the exact mechanism by which USP48 promotes Mdm2 stability.

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As Mdm2 is best known as a critical negative regulator of p53, in the next set of experiments, we analyzed the impact of the observed USP48 mediated Mdm2 stabilization on cellular p53 protein levels and p53 ubiquitination.

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USP48 promotes Mdm2 stability.

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Moreover, two previously characterized USP48 mutants lacking deubiquitinase activity were also capable of efficiently stabilizing Mdm2, indicating that USP48 utilizes a non canonical, deubiquitination independent mechanism to promote Mdm2 oncoprotein stability.
USP48 increases the amount of MDM2.
| 1
USP48 increases the amount of MDM2. 1 / 1
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However, if the active trimming of K48 linked ubiquitin was responsible for Mdm2 stabilization, USP48 protein lacking deubiquitinase activity should not be able to modulate Mdm2 protein levels.
USP48 decreases the amount of MDM2.
| 1
USP48 decreases the amount of MDM2. 1 / 1
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In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels.
USP48 affects BRCA1
| 1 5
USP48 inhibits BRCA1.
| 1 3
USP48 inhibits BRCA1. 4 / 4
| 1 3

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In cells we reveal that USP48 antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48 results in positioning 53BP1 further from the break site and in extended resection lengths.

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USP48 loss enhances BRCA1 and RAD51 localization in FA cells.

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Interestingly , in the absence of USP48 , single-stranded annealing is promoted , which is likely due to the increased resection that occurs if BRCA1 is not properly constrained by USP48 .

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Moreover, both the increased GC and SSA repair seen in USP48 depleted cells required BRCA1, as well as CtIP.
USP48 activates BRCA1.
| 2
USP48 activates BRCA1. 2 / 2
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Thus, high levels or activity of USP48 would be expected to decrease resection lengths and thus reduce GC, and phenocopy aspects of BRCA1 loss.

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We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function.
USP48 affects NFkappaB
| 1 4
USP48 activates NFkappaB.
| 1 2
| 1 2

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However, subsequent studies demonstrated that in fact USP48 promotes NF-kappaB activity by co-operating with the COP9 signalosome to trim K48 linked polyubiquitin chains from p65 in the nucleus [XREF_BIBR].

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The inhibition of NF-κB activation by USP31 was not due to a reduction of effector protein expression, since Western blot analysis revealed that the levels of all effector proteins were unaffected by [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Here, we show that maybe the stability of NF-kappaB is controlled by proteasome mediated degradation and ubiquitin specific protease 48 (USP48), also known as synaptic ubiquitin specific protease (synUSP) or USP31, can enhance NF-kappaB stability through proteasome dependent regulation in the nucleus.
USP48 inhibits NFkappaB.
| 2
| 2

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Depletion of USP48 decreases NF-kappaB target gene expression [XREF_BIBR].

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Initial studies found that overexpression of USP48 inhibits NF-kappaB activity downstream of IKKbeta and that USP48 also interacts with p65.
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Valproic acid increases the amount of USP48. 4 / 4
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CREB1 affects USP48
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CREB1 decreases the amount of USP48. 4 / 4
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Ubiquitin affects USP48
| 3
| 3

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On both substrates the addition of free ubiquitin did activate USP48.

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An auxiliary ubiquitin on the nucleosome promotes USP48 activity.

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Detailed biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin that itself does not get cleaved, modulates USP48 activity, which has possible implications for its regulation in vivo.

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By contrast, USP48 depletion did not enhance MMC induced RAD51 focus formation in control cells, suggesting that USP48 may inhibit HR processes specifically in an FA deficient background.

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As we had found that USP48 loss enhances HR in DeltaFANCC cells, we determined whether it could also alleviate chromosome breaks in DeltaFANCC cells.

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At 18h after MMC treatment, recruitment of RAD51 into foci was significantly higher in U2OS cells simultaneously depleted for both FANCC and USP48 by siRNA treatment, compared to cells depleted for FANCC alone, implying that USP48 loss restores HR efficiency at replication forks encountering ICL damage in FA deficient cells.
Copper(II) sulfate decreases the amount of USP48.
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Copper(II) sulfate decreases the amount of USP48. 2 / 2
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Copper(II) sulfate increases the amount of USP48.
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Copper(II) sulfate increases the amount of USP48. 1 / 1
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USP48 affects SLC9A3
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USP48 activates SLC9A3.
| 2
USP48 activates SLC9A3. 2 / 2
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USP48 silencing decreased NHE3 's half-life (USP48 siRNA t1/2 = 6.1 h vs. vehicle t1/2 = 12.9 h), whereas overexpression of USP48 increased NHE3 half-life (t1/2 = 21.8 h), indicating that USP48 protects NHE3 from degradation via deubiquitinylation.

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That is, the dopamine D3 receptor inhibits USP48 expression, which promotes NHE3 degradation.
USP48 inhibits SLC9A3.
| 1
USP48 inhibits SLC9A3. 1 / 1
| 1

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That is, the dopamine D3 receptor inhibits USP48 expression, which promotes NHE3 degradation.
USP48 affects ICL
| 3
USP48 inhibits ICL. 2 / 2
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Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background.

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Re-introduction of exogenous wild-type USP48, but not the catalytically inactive C98S USP48 mutant, partially reduced ICL resistance of DeltaUSP48DeltaFANCC cells, thus indicating that lack of USP48 catalytic activity is important for the increased survival of DeltaUSP48DeltaFANCC cells.
USP48-C98S inhibits ICL. 1 / 1
| 1

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Re-introduction of exogenous wild-type USP48, but not the catalytically inactive C98S USP48 mutant, partially reduced ICL resistance of DeltaUSP48DeltaFANCC cells, thus indicating that lack of USP48 catalytic activity is important for the increased survival of DeltaUSP48DeltaFANCC cells.
USP48 affects GLI1
| 3
USP48 activates GLI1.
| 2
USP48 activates GLI1. 2 / 2
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In addition to USP7 and OTUB2, the deubiquitinase USP48 was found to activate Hh signaling by stabilizing Gli1 protein in glioma cells [65].
| PMC

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Gli1 induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1.
USP48 increases the amount of GLI1.
| 1
USP48 increases the amount of GLI1. 1 / 1
| 1

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Knockdown of USP48 inhibited the expression of Gli1 target genes and repressed cell proliferation and tumorigenesis [65].
| PMC
| 3
USP48 inhibits E3_Ub_ligase.
| 2
| 2

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Further, USP48 promotes cell survival and antagonizes also other E3 ligase functions which are involved in genome stability and DNA repair.

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In cells we reveal that USP48 antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48 results in positioning 53BP1 further from the break site and in extended resection lengths.
USP48 activates E3_Ub_ligase.
| 1
| 1

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We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function.
GLI1 affects USP48
| 1 2
GLI1 activates USP48.
| 1 1
GLI1 activates USP48. 2 / 2
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Interestingly, USP48 is transcriptionally activated by Gli1 in glioma cells, thus forms a positive feedback loop to regulate Hh signaling [65].
| PMC

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Interestingly, USP48 is transcriptionally activated by Gli1 in glioma cells, thus forms a positive feedback loop to regulate Hh signaling [ xref ].
| PMC
GLI1 increases the amount of USP48.
| 1
GLI1 increases the amount of USP48. 1 / 1
| 1

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We find that deubiquitinase USP48 activates Gli dependent transcription by stabilizing Gli1 protein.
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Hsa-miR-6838-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-646 affects USP48
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Hsa-miR-646 decreases the amount of USP48. 2 / 2
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Hsa-miR-561-3p decreases the amount of USP48. 2 / 2
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Hsa-miR-5590-3p decreases the amount of USP48. 2 / 2
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Hsa-miR-548p decreases the amount of USP48. 2 / 2
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Hsa-miR-548at-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-545-3p decreases the amount of USP48. 2 / 2
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Hsa-miR-503-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-497-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-4524b-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-4524a-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-424-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-374b-3p decreases the amount of USP48. 2 / 2
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Hsa-miR-195-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-16-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-15b-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-15a-5p decreases the amount of USP48. 2 / 2
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Hsa-miR-1468-3p decreases the amount of USP48. 2 / 2
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Hsa-miR-142-5p decreases the amount of USP48. 2 / 2
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Hsa-let-7i-3p decreases the amount of USP48. 2 / 2
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In conclusion, the present study highlights the function of USP48 in the ATRA induced granulocytic differentiation of APL cells and provides a theoretical basis for identifying novel targets for differentiation therapy of APL.

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Deubiquitinase USP48 promotes ATRA induced granulocytic differentiation of acute promyelocytic leukemia cells.

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Deubiquitinase USP48 promotes ATRA induced granulocytic differentiation of acute promyelocytic leukemia cells [XREF_BIBR].

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Deubiquitinase USP48 promotes ATRA induced granulocytic differentiation of acute promyelocytic leukemia cells.
USP48 affects USP48
| 2
USP48 activates USP48. 2 / 2
| 2

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These results indicate that CK2 mediated phosphorylation of USP48 at its C-terminal CK2 consensus sites and its binding to K48 linked Ub-chains, both of which promote USP48 Ub-chain-trimming activity,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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In response to TNF-alpha, serine phosphorylation of USP48 by GSK3beta increases USP48 activity.

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Importantly, the results of the present study show that loss of USP48 improves DNA repair and prevents genomic instability of FA defective cells, thus highlighting the potential of developing USP48 inhibitory molecules as novel therapeutic approaches that could potentially alleviate the phenotypes of FA patients.

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We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function.
USP48 affects CDH1
| 2
USP48 increases the amount of CDH1. 2 / 2
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Inhibition of TRAF2 and JNK pathway increases E-cadherin expression and enhances epithelial barrier integrity, while knockdown of USP48 attenuates TNF-alpha and JNK pathway and increases E-cadherin expression and cell-cell junction in epithelial cells.

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Further, down-regulation of USP48 increases E-cadherin expression and epithelial barrier integrity through reducing TRAF2 stability.-Li, S., Wang, D., Zhao, J., Weathington, N. M., Shang, D., Zhao, Y.
METTL14 affects USP48
| 1 1
METTL14 activates USP48. 2 / 2
| 1 1

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USP48 is upregulated by Mettl14 to attenuate hepatocellular carcinoma via regulating SIRT6 stabilization .

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USP48 is upregulated by Mettl14 to attenuate hepatocellular carcinoma via regulating SIRT6 stabilization.
LINC00467 affects USP48
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LINC00467 increases the amount of USP48. 2 / 2
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LINC00467 could upregulate USP48 expression via sponging miR-299-5p.

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LINC00467 enhances HNSCC progression by serving as a sponge of miR-299-5p to increase USP48 expression.
Hedgehog affects USP48
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Hedgehog increases the amount of USP48. 2 / 2
| 2

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In addition, we find that the Sonic Hedgehog (SHH) pathway induces USP48 expression through Gli1 mediated transcriptional activation, which forms thus a positive feedback loop to regulate Hh signaling.

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USP48 provides a positive feedback loop in Hh signaling as USP48 expression is induced by Hh activation.
ATF3 affects USP48
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ATF3 decreases the amount of USP48. 2 / 2
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Paracetamol affects USP48
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Paracetamol increases the amount of USP48.
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Paracetamol increases the amount of USP48. 1 / 1
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Paracetamol decreases the amount of USP48.
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Paracetamol decreases the amount of USP48. 1 / 1
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Bisphenol A affects USP48
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Bisphenol A increases the amount of USP48.
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Bisphenol A increases the amount of USP48. 1 / 1
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Bisphenol A decreases the amount of USP48.
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Bisphenol A decreases the amount of USP48. 1 / 1
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USP48 affects TRAF2
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USP48 decreases the amount of TRAF2.
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USP48 decreases the amount of TRAF2. 1 / 1
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Down-regulation of USP48 increases K48 linked polyubiquitination of TRAF2 and reduces TRAF2 protein levels.
USP48 activates TRAF2.
| 1
USP48 activates TRAF2. 1 / 1
| 1

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A noteworthy fact is that TRAF2 in JNK pathway was targeted by USP48, but not TRAF2 in NF-kappaB signaling [XREF_BIBR].
USP48 affects RO60
| 2
USP48 inhibits RO60.
| 1
USP48 inhibits RO60. 1 / 1
| 1

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Moreover, we provide evidence that USP48 acts to prevent extensive resection and restrict the use of SSA.
USP48 activates RO60.
| 1
USP48 activates RO60. 1 / 1
| 1

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Depletion of USP48 increases SSA and confers a RAD52 dependent survival benefit to cells treated with camptothecin.
17alpha-ethynylestradiol increases the amount of USP48.
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17alpha-ethynylestradiol increases the amount of USP48. 1 / 1
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17alpha-ethynylestradiol decreases the amount of USP48.
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17alpha-ethynylestradiol decreases the amount of USP48. 1 / 1
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Vinclozolin affects USP48
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Vinclozolin decreases the amount of USP48. 1 / 1
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Tungsten affects USP48
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Tungsten decreases the amount of USP48. 1 / 1
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Methyltestosterone increases the amount of USP48. 1 / 1
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Methylparaben increases the amount of USP48. 1 / 1
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Ionomycin affects USP48
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Ionomycin increases the amount of USP48. 1 / 1
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Hsa-miR-943 affects USP48
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Hsa-miR-943 decreases the amount of USP48. 1 / 1
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Hsa-miR-93-5p decreases the amount of USP48. 1 / 1
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Hsa-miR-892a decreases the amount of USP48. 1 / 1
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Hsa-miR-876-5p decreases the amount of USP48. 1 / 1
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Hsa-miR-8063 decreases the amount of USP48. 1 / 1
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Hsa-miR-7153-5p decreases the amount of USP48. 1 / 1
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Hsa-miR-589-5p decreases the amount of USP48. 1 / 1
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Hsa-miR-580-3p decreases the amount of USP48. 1 / 1
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Hsa-miR-548ah-5p decreases the amount of USP48. 1 / 1
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Hsa-miR-545-5p decreases the amount of USP48. 1 / 1
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Hsa-miR-526b-3p decreases the amount of USP48. 1 / 1
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Hsa-miR-519d-3p decreases the amount of USP48. 1 / 1
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Hsa-miR-4796-3p decreases the amount of USP48. 1 / 1
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Hsa-miR-4539 decreases the amount of USP48. 1 / 1
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No evidence text available
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Hsa-miR-3609 decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3167 decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3118 decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-20b-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-20a-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-17-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-148b-3p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-146b-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-146a-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-134-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-1305 decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-1290 decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-1246 decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-124-3p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-106b-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-106a-5p decreases the amount of USP48. 1 / 1
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biopax:mirtarbase
No evidence text available
Hexabromocyclododecane decreases the amount of USP48. 1 / 1
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ctd
No evidence text available
Gentamycin affects USP48
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Gentamycin increases the amount of USP48. 1 / 1
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ctd
No evidence text available
Flutamide affects USP48
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Flutamide decreases the amount of USP48. 1 / 1
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ctd
No evidence text available
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ctd
No evidence text available
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Dorsomorphin increases the amount of USP48. 1 / 1
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ctd
No evidence text available
Dopamine affects USP48
| 1
Dopamine decreases the amount of USP48. 1 / 1
| 1

reach
That is, the dopamine D3 receptor inhibits USP48 expression, which promotes NHE3 degradation.
Cas9 affects USP48
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Cas9 inhibits USP48. 1 / 1
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sparser
Further confirming that the synthetic rescue was indeed dependent on USP48, when we subjected USP48 to short-hairpin RNA (shRNA) depletion (Supplementary Fig.  xref ) or carried out USP48 gene inactivation by CRISPR-Cas9 editing by using a different single guide (sg)RNA targeting a different exon (Supplementary Fig.  xref ) in Δ FANCC cells, we observed similar results.
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ctd
No evidence text available
Atrazine affects USP48
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Atrazine decreases the amount of USP48. 1 / 1
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ctd
No evidence text available
Apigenin affects USP48
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Apigenin increases the amount of USP48. 1 / 1
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ctd
No evidence text available
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Aflatoxin B1 increases the amount of USP48. 1 / 1
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ctd
No evidence text available
Acrylamide affects USP48
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Acrylamide increases the amount of USP48. 1 / 1
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ctd
No evidence text available
Acetamide affects USP48
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Acetamide decreases the amount of USP48. 1 / 1
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ctd
No evidence text available
ZEB1 affects USP48
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ZEB1 decreases the amount of USP48. 1 / 1
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biopax:msigdb
No evidence text available
ZBTB14 affects USP48
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ZBTB14 decreases the amount of USP48. 1 / 1
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biopax:msigdb
No evidence text available

sparser
We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein.
USP48 affects sodium atom
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reach
We now offer and describe a novel mechanism by which D3R decreases sodium transport in the long term by inhibiting the deubiquitinylating activity of ubiquitin specific peptidase 48 (USP48), thereby promoting Na (+)-H (+) exchanger (NHE) -3 degradation.
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reach
USP48 loss enhances BRCA1 and RAD51 localization in FA cells.

eidos
USP48 is upregulated by Mettl14 to attenuate hepatocellular carcinoma via regulating SIRT6 stabilization .

reach
Notably, the authors in this study showed the activity of USP48 counteracts BRCA1 mediated ubquitylation of H2A K127/129 and thereby preventing chromatin remodeling and resection during double-strand break repair after IR and camptothecin treatment 35.

reach
XREF_BIBR In GBM cells, knockdown of USP48 inhibits cell proliferation and expression of GLI1 's downstream targets, leading to repressed tumorigenesis.
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reach
The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation.
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reach
After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells.
USP48 affects TP53BP1
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reach
USP48 loss increases resection and intriguingly, depletion of USP48 or 53BP1 or their co-depletion, all result in a similar increase in RAD51 foci, suggesting that loss of either protein has a similar impact and acts in the same pathway to restrict RAD51 accumulation.
USP48 affects TNF
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USP48 inhibits TNF. 1 / 1
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sparser
For example, USP11 negatively regulates TNFα-induced NF-κB activation associated with IκBα and attenuates IκBα degradation [34] ; USP20 deubiquitinates TRAF6 and suppresses interleukin 1β (IL-1β)-and Tax-induced NF-κB activation [40] ; Katrin et al. showed that USP15 regulates IκBα/NF-κB by deubiquitinylation IκBα [44] ; and USP31 inhibits TNFα, CD40, TRAF2, TRAF6 and IKKβ-mediated NF-κB activation [45] .
USP48 affects SMARCAD1
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Our data suggest a model in which USP48 mediated removal of the H2A BRCA1ub mark on chromatin restrains subsequent SMARCAD1 function, thereby halting the mobilization of 53BP1 and providing a boundary for resection.
USP48 affects SLX4
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USP48 inhibits SLX4. 1 / 1
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Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background.

reach
USP48 depleted cells showed a slight reduction in NHEJ and slightly increased sensitivity to IR.
USP48 affects RPA
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USP48 activates RPA. 1 / 1
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Irradiated S-phase cells depleted of USP48 had more RPA foci compared with controls and complementation with either siRNA resistant USP48 Iso1 -WT or USP48 Iso2 -WT, but not USP48 Iso2 -C98S, restored RPA foci numbers to control levels.
USP48 affects RELA
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USP48 activates RELA. 1 / 1
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reach
Interestingly, overexpressed USP48 promoted RelA nuclear accumulation 30 min after TNF stimulation independent of catalytic site Cys C98.
USP48 affects RBBP8
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USP48 inhibits RBBP8. 1 / 1
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Moreover, both the increased GC and SSA repair seen in USP48 depleted cells required BRCA1, as well as CtIP.
USP48 affects RAD51
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USP48 inhibits RAD51. 1 / 1
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reach
USP48 loss enhances BRCA1 and RAD51 localization in FA cells.
USP48 affects PARP1
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USP48 activates PARP1. 1 / 1
| 1

reach
After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells.

eidos
The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP , and alleviates the metastasis in vivo .

reach
The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation.
USP48 affects Leu-Ile
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USP48 activates Leu-Ile. 1 / 1
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reach
Surprisingly, USP48 knockdown increased the abundance of lysine 48 (K48)-linked ubiquitination but not the K63 linked ubiquitination of TRAF2, and subsequently reduced its stability (Li et al., 2018b).
USP48 affects IKBKB
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USP48 inhibits IKBKB. 1 / 1
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reach
Initial studies found that overexpression of USP48 inhibits NF-kappaB activity downstream of IKKbeta and that USP48 also interacts with p65.
USP48 affects Hedgehog
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| 1

reach
In addition to USP7 and OTUB2, the deubiquitinase USP48 was found to activate Hh signaling by stabilizing Gli1 protein in glioma cells [65].
| PMC
USP48 affects FSCN1
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USP48 inhibits FSCN1. 1 / 1
| 1

reach
Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background.
USP48 affects FASLG
| 1