USP3 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 3
HGNC Gene Symbol
USP3
Identifiers
hgnc:12626 NCBIGene:9960 uniprot:Q9Y6I4
Orthologs
mgi:2152450 rgd:1308852
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP3
Number of Papers
60 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
RAB8B RAB8B, member RAS oncogene family 0.308 Reactome (2) -0.07 -0.45 3.29e-01
PPIB peptidylprolyl isomerase B 0.221 0.17 0.83 4.29e-03
EID1 EP300 interacting inhibitor of differentiation 1 0.211
CSNK1G1 casein kinase 1 gamma 1 0.193 0.30 1.57 5.77e-06
CGNL1 cingulin like 1 0.193 0.07 0.32 2.51e-01
STUM stum, mechanosensory transduction mediator homolog 0.188
BMI1 BMI1 proto-oncogene, polycomb ring finger 0.188 Reactome (2)

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP3using 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 USP3 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
RPL26 ribosomal protein L26 5.30e-01 1.85e-10 2.05e-07
RPS3 ribosomal protein S3 6.66e-01 1.01e-08 5.60e-06
PSMB1 proteasome 20S subunit beta 1 3.62e-01 6.19e-07 2.28e-04
RPL17 ribosomal protein L17 9.81e-01 1.40e-06 3.86e-04
COX7C cytochrome c oxidase subunit 7C 4.53e-01 4.77e-06 8.77e-04
RPL18 ribosomal protein L18 4.74e-01 3.97e-06 8.77e-04
PPP3CA protein phosphatase 3 catalytic subunit alpha -6.18e-01 2.37e-05 3.37e-03
RPLP2 ribosomal protein lateral stalk subunit P2 5.50e-01 2.44e-05 3.37e-03
TMED2 transmembrane p24 trafficking protein 2 -4.25e-01 1.00e-04 1.23e-02
ACTB actin beta -3.13e-01 1.27e-04 1.40e-02
ATP5PB ATP synthase peripheral stalk-membrane subunit b 3.35e-01 1.62e-04 1.62e-02
MRPS7 mitochondrial ribosomal protein S7 4.12e-01 2.01e-04 1.85e-02
STMN1 stathmin 1 2.74e-01 3.68e-04 3.12e-02
JPT1 Jupiter microtubule associated homolog 1 2.75e-01 6.01e-04 4.48e-02
MYL12B myosin light chain 12B 2.46e-01 6.08e-04 4.48e-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 USP3 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
USP3 deubiquitinates Histone_H2B. 6 / 6
| 6

reach
USP3 dynamically associates with chromatin and deubiquitinates H2A and H2B in vivo.

reach
Usp3 can deubiquitinate both H2A and H2B in humans.

reach
Deubiquitination of histones H2A and H2B by USP3 is required for progression through the S phase and for genomic stability.

reach
In the DDR, USP3 dynamically interacts with chromatin and deubiquitinates H2A and H2B.

reach
In addition to USP22 and its yeast homolog, H2B can be deubiquitylated by USP3 and USP7 in humans.

reach
USP3 that was found as chromatin associated DUB suppresses global mono-ubiquitylation of H2A (and also H2B).
USP3 deubiquitinates DDX58. 4 / 4
| 3

reach
CYLD (cylindromatosis) deubiquitinates RIG-I and several downstream molecules to prevent premature RIG-I activation in uninfected cells [17], while USP3 deubiquitinates RIG-I specifically after viral infection, likely serving as a negative feedback regulator [18].

ubibrowser
USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors

reach
USP3 is also a DUB that deubiquitinates K63-polyUb chain of both RIG-I and MDA5 and suppresses IFN-β activation [25].

reach
CYLD (cylindromatosis) deubiquitinates RIG-I and several downstream molecules to prevent premature RIG-I activation in uninfected cells [XREF_BIBR], while USP3 deubiquitinates RIG-I specifically after viral infection, likely serving as a negative feedback regulator [XREF_BIBR].
USP3 deubiquitinates Histone. 3 / 3
| 3

reach
Notably, USP3 deletion increased the levels of histone ubiquitination in adult tissues, reduced the hematopoietic stem cell (HSC) reserves over time, and shortened animal life span.

reach
Consistently, we found that USP3, which deubiquitylates H2A-type histones to prevent accumulation of RNF168 and downstream repair factors, but not RNF8, at DSB sites, also suppressed RNF169 recruitment in a manner requiring its catalytic activity (XREF_FIG).

reach
Overexpression of USP3 in HeLa cells reduced levels of both Ub-H2A and Ub-H2B, whereas knockdown of USP3 enhanced the ubiquitination of both histones.
USP3 deubiquitinates Histone-H2A. 3 / 3
| 3

reach
RNF168 is an E3 ligase that ubiquitinates histones H2A and gammaH2AX during the DNA damage response [XREF_BIBR], this ubiquitination can be reversed by Usp3 [XREF_BIBR].

reach
Deubiquitination of histones H2A and H2B by USP3 is required for progression through the S phase and for genomic stability.

reach
Several DUBs have been implicated in histone deubiquitination, including USP3, USP12, USP22, and USP46, which deubiquitinate both histones H2A and histones H2B [XREF_BIBR].
USP3 leads to the deubiquitination of KLF5. 2 / 2
| 1

ubibrowser
In this study, ubiquitin-specific protease 3 (USP3) was identified as a new KLF5 deubiquitinase by genome-wide siRNA library screening.

reach
USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5.
USP3 deubiquitinates COL6A5. 1 / 1
| 1

reach
These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5.
USP3 deubiquitinates H2AC17. 1 / 1
|

ubibrowser
USP3 and USP16 function to remove ubiquitin from histone H2A during the DDR
USP3 deubiquitinates H2AX. 1 / 1
|

ubibrowser
Review
USP3 deubiquitinates CHEK1. 1 / 1
|

ubibrowser
Herein, we show that the K63-linked ubiquitin chain at CHK1's K132 residue has an inhibitory effect on the kinase activity. Furthermore, we demonstrate that this modification can be removed by ubiquitin-specific protease 3 (USP3), a deubiquitinating enzyme that targets K63-linked ubiquitin chains.
USP3 deubiquitinates H2BC10. 1 / 1
|

ubibrowser
Here we identify the ubiquitin-specific protease 3 USP3 as a deubiquitinating enzyme for uH2A and uH2B.
USP3 deubiquitinates H2BC21. 1 / 1
|

ubibrowser
USP3 dynamically associates with chromatin and deubiquitinates H2A/H2B in vivo.
USP3 deubiquitinates NANOG. 1 / 1
|

ubibrowser
Review
USP3 deubiquitinates H2AC20. 1 / 1
|

ubibrowser
USP3 counteracts RNF168 via deubiquitinating H2A and gammaH2AX at lysine 13 and 15.
USP3 leads to the deubiquitination of MYCN. 1 / 1
| 1

reach
The known role of ALYREF as a regulator of DNA binding guided further analyses that uncovered ALYREF-MYCN interaction in a nuclear coactivator complex which stimulates transcription of the ‘ubiquitin specific peptidase 3′ (USP3), consequently reducing MYCN ubiquitination and degradation.
| PMC
USP3 deubiquitinates COL9A3. 1 / 1
| 1

reach
These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5.
USP3 deubiquitinates UIMC1. 1 / 1
|

ubibrowser
K63-linked ubiquitin accumulates on Rap80 at the DSB foci with the concerted effect of RNF8, RNF168, and Ubc13, which are clipped off with the assistance of USP3 and BRCC36 to maintain the G2/M checkpoint.
USP3 deubiquitinates IFIH1. 1 / 1
| 1

reach
USP3 is also a DUB that deubiquitinates K63-polyUb chain of both RIG-I and MDA5 and suppresses IFN-β activation [25].
USP3 deubiquitinates SUZ12. 1 / 1
|

ubibrowser
We observed that USP3 interacted with and stabilized SUZ12 via deubiquitination.
USP3 deubiquitinates TP53. 1 / 1
|

ubibrowser
Depletion of USP3 lead to accelerated degradation of p53 in normal cells thereby enhanced cell proliferation and transformation.
USP3 deubiquitinates Histone_H2A on K13. 1 / 1
| 1

trips
USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15.

Other Statements

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

reach
USP3 knockdown inhibits breast cancer cell proliferation in vitro and tumorigenesis in vivo, which can be partially rescued by ectopic expression of KLF5.

reach
Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion.

reach
Upregulation of USP3 or downregulation of miR-224-5p restored proliferation and migration by MKN-28 and MGC-803 cells after hsa_circ_0017639 silencing.

reach
Therefore, USP3 might accelerate the proliferation of NSCLC cells via regulating RBM4.

reach
Upregulation of USP3 restored MKN-28 and MGC-803 cell proliferation and migration after overexpression of miR-224-5p.

reach
Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC.

reach
USP3 promotes proliferation of non small cell lung cancer through regulating RBM4.

reach
Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma.

reach
In vivo deletion of USP3, a deubiquitinating enzyme involved in DNA damage repair, increases the incidence of spontaneous cancer and impairs the proliferation and repopulation ability of HSCs.

reach
Silencing of USP3 suppressed GC cell proliferation and spreading in vitro as well as xenograft proliferation and metastasis in vivo; however, opposite results were obtained when USP3 was overexpressed.

reach
Depletion of tyrosine tRNA GUA or its translationally regulated targets USP3 and SCD repressed proliferation revealing a dedicated tRNA regulated growth-suppressive pathway for oxidative stress response.
| 3 8
| 3 6

eidos
These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5 .

reach
USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation.

reach
Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC.

reach
Silencing of USP3 suppressed GC cell proliferation and spreading in vitro as well as xenograft proliferation and metastasis in vivo; however, opposite results were obtained when USP3 was overexpressed.

reach
USP3 knockdown induced metastasis was abolished by USP3 3 ' UTR overexpression in CRC cells.

reach
However, the mechanism by which USP3 promotes gastric cancer (GC) metastasis remains largely unknown.

eidos
Hsa_circ_0017639 expression promotes gastric cancer proliferation and metastasis by sponging miR-224-5p and upregulating USP3 .

reach
Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma.

eidos
USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3 / COL6A5 stabilisation .
| 2

reach
USP3 and SMAD4 were directly targeted by miR-224, and overexpression of the USP3 3 ' UTR could inhibit metastasis caused by the loss of USP3.

reach
These results indicated that the loss of USP3 facilitated tumour progression, while overexpression of the USP3 3 ' UTR inhibited metastasis in CRC cells.
USP3 affects DDX58
| 1 8
USP3 inhibits DDX58.
| 1 7
USP3 inhibits DDX58. 8 / 10
| 1 7

sparser
While the deubiquitinase USP3 inhibits MDA5 as well as RIG-I, it is thought that this may be due to USP3 directly binding the MDA5 CARD domain to prevent RNA filamentation (284).

reach
Our findings identify a previously unrecognized role of USP3 in RIG-I activation and provide insights into the mechanisms by which USP3 inhibits RIG-I signaling and antiviral immunity.

reach
USP3, USP21 and CYLD inhibit RIG-I K63-linked ubiquitination and activation.

reach
In particular, USP3, USP21, USP25 and USP15 have all been shown to directly inhibit RIG-I.

reach
Conversely, the removal of Lys63-linked ubiquitylation by the cellular deubiquitylating enzymes (DUBs) ubiquitin C-terminal hydrolase 3 (USP3), USP21 and CYLD, represses RIG-I signalling (reviewed in REF.

reach
While the deubiquitinase USP3 inhibits MDA5 as well as RIG-I, it is thought that this may be due to USP3 directly binding the MDA5 CARD domain to prevent RNA filamentation (284).

reach
The deubiquitinases USP3 and USP21 inhibit RIG-I activity by removing K63-linked ubiquitin chains.
| PMC

reach
Conversely, the removal of Lys63 linked ubiquitylation by the cellular deubiquitylating enzymes (DUBs) ubiquitin C-terminal hydrolase 3 (USP3), USP21 and CYLD, represses RIG-I signalling.
USP3 activates DDX58.
| 1
USP3 activates DDX58. 1 / 1
| 1

reach
Ubiquitylation events are reversible processes, and, accordingly, several deubiquitylating enzymes, in particular ubiquitin specific peptidase 3 (USP3), USP21 and CYLD lysine 63 deubiquitinase (CYLD), modulate RIG-I signalling by removing K63-polyubiquitin chains, although with unique kinetics.
USP3 affects RNF168
| 8
USP3 inhibits RNF168. 8 / 10
| 8

reach
Similar to USP26 and USP37, two other DUBs, USP3 and USP44, were shown to reverse RNF168 induced chromatin ubiquitylation, thereby controlling the accumulation of BRCA1 and 53BP1 at sites of DNA damage.

reach
By virtue of its ability to oppose histone H2A ubiquitylation and the fact that USP3 over-expression can block accumulation of the ubiquitin E3 ligase RNF168 at DSB sites, USP3 has been linked to the key RNF8-RNF168 pathway of assembling repair and signalling components at DSB sites [XREF_BIBR].

reach
Overexpression of USP3, a deubiquitylating enzyme that reversed H2A ubiquitylation, as well as mutations in the UIM domains of RNF168, prevented the accumulation of RNF168 at DSBs.

reach
The DUBs USP3, USP16, BRCC36, POH1, and OTUB1 are associated with negative regulation of the RNF8 pathway, with USP3 and USP16 being first linked to this pathway through their ability to oppose H2A ub[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
In this context, overexpression of wild-type USP3, but not its catalytically inactive mutant, prevented the IR induced focus formation of RNF168, emphasizing the requirement of UPS3 cysteine protease activity to reverse the DSB ubiquitin response at the level of RNF8 XREF_BIBR.

reach
By virtue of its ability to oppose histone H2A ubiquitylation and the fact that USP3 over-expression can block accumulation of the ubiquitin E3 ligase RNF168 at DSB sites, USP3 has been linked to the key RNF8–RNF168 pathway of assembling repair and signalling components at DSB sites [84].

reach
In this context, overexpression of wild-type USP3, but not its catalytically inactive mutant, prevented the IR induced focus formation of RNF168, emphasizing the requirement of UPS3 cysteine protease [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
But most significantly in this context, overexpression of wild-type USP3, but not its catalytically inactive mutant, prevented the IR induced focus formation of RNF168, indicating that the assembly of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP3 affects Ubiquitin
| 1 8
USP3 inhibits Ubiquitin.
| 1 3
| 1 3

reach
By virtue of its ability to oppose histone H2A ubiquitylation and the fact that USP3 over-expression can block accumulation of the ubiquitin E3 ligase RNF168 at DSB sites, USP3 has been linked to the key RNF8–RNF168 pathway of assembling repair and signalling components at DSB sites [84].

reach
The Ub modifications on K119/120 of histone H2A and K13/15 of histone H2B generated by BMI1 and RNF2 and RNF20-RNF40 are attenuated by USP3, an H2A and H2B specific DUB.

trips
We further identified that the USP3 removes Ub at lysine 13 and 15 of H2A and γH2AX, as well as lysine 118 and 119 of H2AX in response to DNA damage.

reach
By virtue of its ability to oppose histone H2A ubiquitylation and the fact that USP3 over-expression can block accumulation of the ubiquitin E3 ligase RNF168 at DSB sites, USP3 has been linked to the key RNF8-RNF168 pathway of assembling repair and signalling components at DSB sites [XREF_BIBR].
USP3 activates Ubiquitin.
| 5
| 5

reach
The data relate to the research article " Tight regulation of ubiquitin mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells " (Lancini et al., 2014) XREF_BIBR.

reach
The USP3 protein is a functional ubiquitin specific protease in vitro, and is able to inhibit ubiquitin dependent degradation of both an N-end Rule substrate and abnormal endogenous proteins in yeast.

reach
Paradoxically, by removing the bulky ubiquitin chain at the active site, USP3 also increased the accessibility of CHK1 to its substrates.

reach
The data relate to the research article " Tight regulation of ubiquitin mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells " (Lancini et al., 2014) [4].

reach
Tight regulation of ubiquitin mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells.
JUN affects USP3
7 |
JUN decreases the amount of USP3. 7 / 7
7 |

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
USP3 affects IFNB1
| 7
USP3 inhibits IFNB1.
| 4
USP3 inhibits IFNB1. 4 / 4
| 4

reach
Ectopic expression of USP3 inhibited IFN-beta promoter activity in cells treated with high molecular weight (HMW) poly (I : C), whereas gene silencing of USP3 enhanced IFN-beta protein expression under similar treatment.

reach
Cellular ubiquitin specific proteases, USP21, USP3 and USP15, a subfamily of deubiqutinase, remove K63 linked polyubiquitin chains from RIG-I and block it to induce IFN-beta.

reach
The ectopic expression of USP3 in HEK293T cells that are treated with low molecular weight poly (I : C) and THP-1 cells infected with VSV attenuated the IFN-beta promoter activity.

reach
Ectopic expression of USP3 inhibited IFN-beta promoter activity in cells treated with low molecular weight (LMW) poly (I : C), and in cells infected with VSV.
USP3 decreases the amount of IFNB1.
| 3
USP3 decreases the amount of IFNB1. 3 / 3
| 3

reach
Gene silencing of USP3 enhanced IFN-beta protein expression under similar treatments.

reach
Ectopic expression of USP3 inhibited IFN-beta promoter activity in cells treated with high molecular weight (HMW) poly (I : C), whereas gene silencing of USP3 enhanced IFN-beta protein expression under similar treatment.

reach
Conversely, the silencing of USP3 enhanced the phosphorylation of IRF3 and IFN-beta protein expression under similar conditions.
USP3 affects MAVS
| 1 2 2
USP3 inhibits MAVS. 5 / 5
| 1 2 2

eidos
USP3 did not inhibit MAVS , STING , TBK1 , IRF3 and TIRF , as demonstrated by ISRE-luc activity induction test [ 25 ] .

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [ xref ].

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [25].

reach
Notably, USP3 inhibited signaling by the constitutively active, truncated form of RIG-I (N-RIG-I), but did not inhibit MAVS signaling.

reach
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [XREF_BIBR].
| 3 1
| 3 1

eidos
USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3 / COL6A5 stabilisation .

eidos
These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5 .

reach
Silencing of USP3 suppressed GC cell proliferation and spreading in vitro as well as xenograft proliferation and metastasis in vivo; however, opposite results were obtained when USP3 was overexpressed.

eidos
Hsa_circ_0017639 expression promotes gastric cancer proliferation and metastasis by sponging miR-224-5p and upregulating USP3 .
USP3 affects Interferon
| 1 3
USP3 inhibits Interferon.
| 1 2
| 1 2

eidos
USP3 inhibits type I interferon signaling by deubiquitinating RIG-Ilike receptors .

reach
USP3 also negatively regulates IFN signaling by interacting with RIG-I and MDA5, but not with other downstream signaling proteins like MAVS, TBK1, IKKi, IRF3, TRAF3, or TRAF6.

reach
USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors.
USP3 increases the amount of Interferon.
| 1
USP3 increases the amount of Interferon. 1 / 1
| 1

reach
Several other DUBs have also been implicated in the regulation of RIG-I ubiquitination and virus induced type I IFN expression; these include A20, USP3, USP15, USP21, and USP25 XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR.
USP3 affects IRF3
| 1 2 1
USP3 inhibits IRF3.
| 1 2
USP3 inhibits IRF3. 3 / 3
| 1 2

eidos
USP3 did not inhibit MAVS , STING , TBK1 , IRF3 and TIRF , as demonstrated by ISRE-luc activity induction test [ 25 ] .

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [ xref ].

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [25].
USP3 decreases the amount of IRF3.
| 1
USP3 decreases the amount of IRF3. 1 / 1
| 1

reach
Conversely, the silencing of USP3 enhanced the phosphorylation of IRF3 and IFN-beta protein expression under similar conditions.
4 |
Pirinixic acid increases the amount of USP3.
2 |
Pirinixic acid increases the amount of USP3. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Pirinixic acid decreases the amount of USP3.
1 |
Pirinixic acid decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Pirinixic acid activates USP3.
1 |
1 |

ctd
No evidence text available
USP3 affects His2A
| 4
USP3 inhibits His2A.
| 2
USP3 inhibits His2A. 2 / 2
| 2

reach
Overexpression of Usp3 in HeLa cells causes the reduction in both uH2A and uH2B without altering the bulk pool of ubiquitinated proteins.

reach
Only wild-type USP3 significantly reduced the total pool of uH2A, showing that both protease activity and an intact zinc finger are required for H2A deubiquitination.
USP3 decreases the amount of His2A.
| 1
Modified USP3 decreases the amount of His2A. 1 / 1
| 1

reach
Overexpression of USP3 in HeLa cells reduced levels of both Ub-H2A and Ub-H2B, whereas knockdown of USP3 enhanced the ubiquitination of both histones.
USP3 activates His2A.
| 1
USP3 activates His2A. 1 / 1
| 1

reach
For example, one could propose that USP3 might specifically target the pool of Ub-H2A that accumulates at DNA repair foci, or that MYSM1 and USP16 are recruited to different cohorts of gene promoters.
3 |
Cyclosporin A increases the amount of USP3. 3 / 3
3 |

ctd
No evidence text available

ctd
No evidence text available

ctd
No evidence text available
| 3

reach
USP3 overexpression inhibited IL-1beta induced chondrocytes apoptosis and nuclear factor kappaB (NF-kappaB) activation.

reach
Despite it has been demonstrated that ubiquitin-specific protease 3 (USP3) inhibits chondrocyte apoptosis induced by interleukin (IL)-1β, the role of USP3/SIRT3/FOXO3 in the senescence of chondrocytes in OA is unclear.

reach
USP3 knockdown induced chondrocytes apoptosis and activated NF-kappaB pathway.
USP3 affects TBK1
| 1 2
USP3 inhibits TBK1. 3 / 3
| 1 2

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [ xref ].

eidos
USP3 did not inhibit MAVS , STING , TBK1 , IRF3 and TIRF , as demonstrated by ISRE-luc activity induction test [ 25 ] .

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [25].
USP3 affects STING1
| 1 2
USP3 inhibits STING1. 3 / 3
| 1 2

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [ xref ].

sparser
USP3 did not inhibit MAVS, STING, TBK1, IRF3 and TIRF, as demonstrated by ISRE-luc activity induction test [25].

eidos
USP3 did not inhibit MAVS , STING , TBK1 , IRF3 and TIRF , as demonstrated by ISRE-luc activity induction test [ 25 ] .
USP3 affects IFIH1
| 1 2
USP3 inhibits IFIH1. 3 / 3
| 1 2

reach
While the deubiquitinase USP3 inhibits MDA5 as well as RIG-I, it is thought that this may be due to USP3 directly binding the MDA5 CARD domain to prevent RNA filamentation (284).

reach
USP3 and USP21 inhibit MDA5 function via deubiquitination XREF_BIBR, XREF_BIBR, and proteins such as dihydroxyacetone kinase (DAK), Atg5-Atg-12, NLRC5, and TRIM13 interact with and inhibit MDA5 XREF_BIBR, XREF_BIBR - XREF_BIBR.

sparser
While the deubiquitinase USP3 inhibits MDA5 as well as RIG-I, it is thought that this may be due to USP3 directly binding the MDA5 CARD domain to prevent RNA filamentation (284).
HNF1A affects USP3
3 |
HNF1A decreases the amount of USP3. 3 / 3
3 |

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
Bisphenol A affects USP3
3 |
Bisphenol A increases the amount of USP3.
2 |
Bisphenol A increases the amount of USP3. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Bisphenol A decreases the amount of USP3.
1 |
Bisphenol A decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
USP3 affects TP53BP1
| 3
USP3 inhibits TP53BP1.
| 2
USP3 inhibits TP53BP1. 2 / 2
| 2

reach
Overexpression of USP3, while having no effect on retention of RNF8 at DSBs, abolished the IR induced focus formation of RNF168, RAP80, and 53BP1, indicating that it de-ubiquitylates RNF8 targeted substrates.

reach
In addition, USP3 overexpression impaired the accumulation of downstream repair factors BRCA1 and 53BP1 at the damage sites in response to both UV and gamma irradiation.
USP3 activates TP53BP1.
| 1
USP3 activates TP53BP1. 1 / 1
| 1

reach
Furthermore, although depletion of USP3 or RNF169, two established regulators of RNF168 controlled events (Doil et al., 2009; Poulsen et al., 2012), increased 53BP1 foci intensity, this effect was con[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
The inhibition of USP3 by PEITC in living cells was confirmed by observing the molecular shift upon probe labeling by immunoblotting.

sparser
The inhibition of USP3 by PEITC in living cells was confirmed by observing the molecular shift upon probe labeling by immunoblotting (Figure xref ).
2 |
Hsa-miR-26b-5p decreases the amount of USP3. 2 / 2
2 |

biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
| 2

reach
USP2b, USP3, USP18, USP25, UL36USP and HAUSP play a role of antivirus; while USP4, USP13, USP15 and USP17 negatively regulate antiviral immune response.

reach
Our findings identify a previously unrecognized role of USP3 in RIG-I activation and provide insights into the mechanisms by which USP3 inhibits RIG-I signaling and antiviral immunity.
USP3 affects ecdysone
| 2
USP3 activates ecdysone. 2 / 2
| 2

reach
Activation of BrC-Z1 as well as EcR, itself an ecdysone response gene, can be mediated by both the USP3 and USP4 mutant proteins.

reach
USP3 and USP4 also activate an ecdysone responsive element, hsp27EcRE, in cultured cells.
USP3 affects SMAD4
| 2
USP3 increases the amount of SMAD4. 2 / 2
| 2

reach
USP3 modulated SMAD4 expression at the post-transcriptional level.

reach
In the present study, we found that USP3 modulated SMAD4 expression in a miRNA dependent, and protein coding gene independent manner.
USP3 affects Neoplasms
| 1
| 1

eidos
Our previous study revealed that USP3 promotes tumour progression and is highly expressed in gastric cancer ( GC ) .

reach
Silencing of USP3 attenuates the migration and invasion abilities of GBM cells in vitro and tumor growth in an orthotopic xenograft mouse model.

reach
Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion.

reach
Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC.

reach
Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma.
LEF1 affects USP3
2 |
LEF1 decreases the amount of USP3. 2 / 2
2 |

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
FOXO4 affects USP3
2 |
FOXO4 decreases the amount of USP3. 2 / 2
2 |

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
ETS2 affects USP3
2 |
ETS2 decreases the amount of USP3. 2 / 2
2 |

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
2 |
Valproic acid increases the amount of USP3.
1 |
Valproic acid increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Valproic acid decreases the amount of USP3.
1 |
Valproic acid decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Phorbol 13-acetate 12-myristate increases the amount of USP3.
| 1
| 1

reach
Levels of USP3, one of the deubiquitinating enzymes (DUBs), increased by TPA treatment, resulting in the reduction of H2AK119ub levels.
Phorbol 13-acetate 12-myristate decreases the amount of USP3.
1 |
1 |

ctd
No evidence text available
USP3 affects H2B
| 2
USP3 inhibits H2B.
| 1
USP3 inhibits H2B. 1 / 1
| 1

reach
Overexpression of Usp3 in HeLa cells causes the reduction in both uH2A and uH2B without altering the bulk pool of ubiquitinated proteins.
USP3 decreases the amount of H2B.
| 1
Modified USP3 decreases the amount of H2B. 1 / 1
| 1

reach
Overexpression of USP3 in HeLa cells reduced levels of both Ub-H2A and Ub-H2B, whereas knockdown of USP3 enhanced the ubiquitination of both histones.
USP3 affects CHEK1
| 2
USP3 inhibits CHEK1.
| 1
USP3 inhibits CHEK1. 1 / 1
| 1

reach
Wild-type USP3, but not the catalytically defective or nuclear localization sequence deficient mutants, reduced CHK1 K63 linked ubiquitination.
USP3 activates CHEK1.
| 1
USP3 activates CHEK1. 1 / 1
| 1

reach
Paradoxically, by removing the bulky ubiquitin chain at the active site, USP3 also increased the accessibility of CHK1 to its substrates.
2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP3.
1 |
1 |

ctd
No evidence text available
2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP3.
1 |
1 |

ctd
No evidence text available

ctd
No evidence text available
1 |
Trichostatin A increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Topotecan affects USP3
1 |
Topotecan decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Titanium dioxide increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Thioacetamide increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Selenium atom decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Rosiglitazone increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Pentachlorophenol decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Oxaliplatin affects USP3
1 |
Oxaliplatin decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Nefazodone affects USP3
1 |
Nefazodone increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Mono(2-ethylhexyl) phthalate decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Methyl methanesulfonate decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Methotrexate affects USP3
1 |
Methotrexate decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Metformin affects USP3
1 |
Metformin increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Isotretinoin affects USP3
1 |
Isotretinoin decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Ionomycin affects USP3
1 |
Ionomycin decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Ifosfamide affects USP3
1 |
Ifosfamide increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-98-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-93-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6734-3p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-670-3p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-519d-3p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-4279 affects USP3
1 |
Hsa-miR-4279 decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3667-3p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-337-3p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-26a-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-20b-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-20a-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-202-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-195-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-18a-3p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-17-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-16-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-15b-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-15a-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-10b-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-106b-5p decreases the amount of USP3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hexabromocyclododecane decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Gentamycin affects USP3
1 |
Gentamycin increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Formaldehyde affects USP3
1 |
Formaldehyde decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Flutamide affects USP3
1 |
Flutamide increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Fenofibrate affects USP3
1 |
Fenofibrate increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Ethyl methanesulfonate decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Dioxygen affects USP3
1 |
Dioxygen increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Diarsenic trioxide increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Dexamethasone increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Coumestrol affects USP3
1 |
Coumestrol decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Copper(II) sulfate increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Chloroacetaldehyde increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Carbon nanotube increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
1 |
Benzo[a]pyrene increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Benzo[a]pyrene diol epoxide I decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Benzene affects USP3
1 |
Benzene increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Aflatoxin B1 affects USP3
1 |
Aflatoxin B1 increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Abrine affects USP3
1 |
Abrine increases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
Vitamin E affects USP3
1 |
Vitamin E decreases the amount of USP3. 1 / 1
1 |

ctd
No evidence text available
USP44 affects USP3
| 1
USP44 activates USP3. 1 / 1
| 1

reach
Similarly to USP3, USP44 can target the most common H2AK119ub mark and displace RNF168 and 53BP1 from IRIF [60,61].
USP3 affects span
| 1
USP3 inhibits span. 1 / 1
| 1

reach
Loss of USP3 leads to shorter life span and increased cancer incidence.

reach
In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation.

reach
Taken together, our data indicate that USP3 promotes TPA mediated leukemia cell differentiation via regulating H2AK119ub levels.

reach
Together, these data demonstrate that USP3 deficient HSCs are more sensitive to genotoxic stress in vivo and in vitro and support the notion that unresolved DNA damage affects the functional integrity of Usp3Delta and Delta HSCs in homeostasis, as well as upon aging and stress.
USP3 affects hemopoiesis
| 1
| 1

reach
Collectively, these findings experimentally support a predominantly cell-autonomous function of USP3 in HSCs under both homeostatic conditions and stress induced hematopoiesis.