IndraLab

Statements



sparser
"Elevated expression of MALAT1, USP3-AS1, and LINC-PINT correlated with worse clinical outcomes in BC patients."

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"Overexpression of USP3-AS1 significantly enhanced both sphere formation efficiency and liver metastasis in PDOs."

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"Gene set enrichment analysis revealed that USP3-AS1 upregulation significantly enriched glycolysis and MYC signaling pathways."

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"We found that USP3-AS1 was significantly upregulated in CRLM-derived PDOs compared to primary tumors."

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"High level of USP3-AS1 was positively associated with postoperative liver metastasis and negatively correlated with the prognosis of colorectal cancer (CRC) patients."

sparser
"Metabolomics analysis confirmed that USP3-AS1 promoted glycolysis in PDOs, whereas glycolysis inhibition partially attenuated the effects of USP3-AS1 overexpression on PDO growth and liver metastasis."

sparser
"We revealed that USP3-AS1 stabilized MYC via post-translational deubiquitination, thereby promoting glycolysis."

sparser
"We demonstrated that USP3-AS1 increased the stability of USP3 mRNA, resulting in higher USP3 protein expression."

sparser
"In addition, VIM-AS1 promoted keratinocyte proliferation, whereas SMAD5-AS1, USP3-AS1, LINC02035, and STARD4-AS1 mediated the opposite effect."

sparser
"In conclusion, USP3-AS1 is a novel promoter of CRLM by inducing histone lactylation."

sparser
"Our data showed strong positive correlations between MALAT1 expression and the expression of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5 (Fig. xref ), highlighting a plausible reciprocal relationship between MALAT1 and the identified lncRNAs in TNBC."

sparser
"We suggest a possible reciprocal relationship between MALAT1 and each of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5."

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"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."

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"Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion."

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

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

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"USP3 promotes the proliferation, migration and invasion of OS cells."

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"However, it is unknown whether these three proteins are involved in the USP3-directed proliferation of GC cells, and future studies should examine their oncogenic roles in GC."

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"USP3 knockdown inhibited the proliferation of breast cancer cells, while ectopic expression of KLF5 partially rescued this inhibitory effect (78)."

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"In contrast, overexpression of USP3 promoted cell proliferation, migration, and invasion."

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"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."

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

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"Our investigation also found that USP3 overexpression suppressed GC cell migration and proliferation, suggesting that USP3 was a miR-224-5p downstream target.In summary, we identified that hsa_circ_00[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Through in vitro cell proliferation (Fig. 2C), colony formation (Fig. 2D), migration (Fig. 2E), wound healing (Supplemental Fig. 1C) and invasion (Fig. 2F) assay, we found that downregulation of USP3 inhibited the proliferation, migration and invasion of osteosarcoma cells."

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"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."

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"Knockdown of USP3 in U2OS cells with two different shRNAs significantly enhanced cell proliferation ( Fig. 4 a)."

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"When we reconstitute WT USP3, but not the C168S catalytic-dead mutant USP3 in the knowdown cells, we found that reconstitution of WT USP3 reversed the increased proliferation caused by USP3 deficiency[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Clone formation ( Fig. 5 E–G) and Transwell ( Fig. 5 H–J) assays validated that USP3 upregulation reversed miR-224-5p-induced inhibition of migration and proliferation in MKN-28 and AMGC803 cells.Poor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The absence of USP3 in vitro and in vivo models has been shown to decrease NB cell proliferation, migration, and invasion and inhibit tumor growth (43)."

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"Additionally, overexpressed USP3 significantly promoted cell proliferation in vitro and tumor growth in vivo, while the silencing of USP3 inhibited proliferation and tumor growth."
USP3 affects MYD88
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USP3 binds MYD88.
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sparser
"USP3 is a key component of the MyD88-USP3 axis, essential for the development of innate immune tolerance [ xref ]."

sparser
"Specifically, using recombinant proteins, we showed that USP3 and MyD88 interacted directly in vitro (Fig  xref )."

sparser
"Our results showed that both USP3 domains could bind to MyD88, but the ZnF domain exhibited a stronger binding ability with MyD88 (Fig  xref )."

sparser
"To determine the physiological relevance of these findings, we stimulated the THP‐1 cells or peripheral blood mononuclear cells (PBMCs) with LPS and found that the interaction between MyD88 and USP3 was induced by LPS treatment and peaked at 60 min after LPS treatment, which correlated with p‐IKK activation (Fig  xref )."

sparser
"Furthermore, to identify the region of USP3 binding to MyD88, we generated two deletion mutants of USP3 containing the zinc‐finger Ub‐binding domain (ZnF‐UBP) (referred to as ZnF) or ubiquitin‐specific protease catalytic domain (UCH)."

sparser
"However, an in vitro binding assay using recombinant MyD88 showed that neither of the individual domains of USP3 could directly interact with non‐ubiquitinated MyD88 purified from E. coli (Fig  xref )."

sparser
"This work identifies a previously unrecognized post‐translational feedback loop in the MyD88USP3 axis, which is critical for inducing normal “tolerance” innate immune memory."

sparser
"This indicates that the intact structure of USP3 is critical for its direct interaction with MyD88, and the interaction between individual domains of USP3 with MyD88 shown in Fig  xref may be attributed to the ubiquitination of MyD88."

sparser
"Next, we tested whether the individual domains of USP3 interact selectively with specific ubiquitinated domains of MyD88."

sparser
"Our results revealed that the ZnF domain of USP3 strongly interacted with both domains of MyD88, while the UCH domain of USP3 interacted with the TIR domain of MyD88 but not the DD domain (Fig  xref )."
USP3 deubiquitinates MYD88.
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USP3 deubiquitinates MYD88. 4 / 4
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"To further understand how USP3 deubiquitinates the MyD88, we generated an inactive catalytic mutant of USP3 (C168S) and a USP3 mutant (H56A) with a disrupted zinc‐finger structure."

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"Co‐IP data revealed that USP3 co‐expression cannot disrupt the interaction between MyD88 and TRAF6, while the interaction between MyD88 and TAK1 is severely interrupted (Fig EV3L and M), indicating that the deubiquitination of MyD88 by USP3 may interrupt TAK1 recruitment."

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"To test this possibility, we performed ubiquitination assays and found that USP3 markedly reduced both total ubiquitination and the K63‐linked ubiquitination of MyD88."

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"Furthermore, MyD88 underwent K63‐linked ubiquitination after LPS treatment in THP‐1 cells, and USP3 deficiency dramatically enhanced the K63‐linked ubiquitination of MyD88 (Fig 4D)."
USP3 inhibits MYD88.
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USP3 inhibits MYD88. 3 / 3
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"We intend to perform long‐term experiments to investigate the duration of innate immune tolerance involving USP3 in the future.Although we found that USP3 inhibits MyD88‐dependent NF‐κB signaling activation by removing the K63‐linked polyubiquitin chains on MyD88, it remains unclear why K63‐linked polyubiquitin chains are so crucial for MyD88‐dependent NF‐κB signaling activation."

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"To identify the molecular target of USP3, we co‐transfected USP3 with different signaling proteins in the NF‐κB pathway and found that USP3 mainly inhibited MyD88‐induced NF‐κB activation and slightly but significantly inhibited TRAF6‐induced NF‐κB activity only at a high USP3 concentration (Fig 3A)."

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"USP3 inhibits NF-kappaB signaling by targeting MyD88."
USP3 ubiquitinates MYD88.
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USP3 ubiquitinates MYD88. 1 / 1
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"USP3 inhibits NF-kappaB activation by deubiquitinating MyD88."
USP3 affects RIGI
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USP3 binds RIGI.
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"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63 linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [XREF_BIBR], we focused on SRSF1 for further experiments."

sparser
"Notably, at the resting state, USP3 does not bind RIG-I, and upon viral infection, an induced USP3 binding to RIG-I leads to the removal of K63-linked ubiquitin chains to restrain or terminate RIG-I signaling ( xref )."

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"USP3 binds RIG-I and removes the K63-polyubiquitin chains on the N-terminal CARDs [XREF_BIBR]."

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"Upon virus infection, USP3 interacted with RIG-I, likely acting as a negative feedback regulator."

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"We found that USP3 and a splicing-factor oncoprotein, serine/arginine rich splicing factor 1 (SRSF1), interact with RIG-I."

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"Coimmunoprecipitation and western blot analyses revealed that USP3 and SRSF1 specifically interact with RIG-I in vitro (XREF_FIG and XREF_SUPPLEMENTARY)."

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"Notably, at the resting state, USP3 does not bind RIG-I, and upon viral infection, an induced USP3 binding to RIG-I leads to the removal of K63-linked ubiquitin chains to restrain or terminate RIG-I signaling (133)."
USP3 binds RIGI and IFIH1. 2 / 2
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sparser
"The interaction of USP3 with RIG-I and MDA5 is strictly based upon ligand stimulation."

sparser
"Also co-IP demonstrated the interaction between USP3 and stimulated RIG-I or MDA5, but not the unstimulated ones, supporting that ligand stimulation is required for USP3 to interact with RIG-I or MDA5 [ xref ]."
UBC binds USP3 and RIGI. 1 / 1
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sparser
"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63-linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [ xref ], we focused on SRSF1 for further experiments."
USP3 binds SRSF1 and RIGI. 1 / 1
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sparser
"To examine which proteins directly interact with RIG-I, we transfected 293T cells with HA-tagged candidate genes together with Flag-tagged RIG-I. Coimmunoprecipitation and western blot analyses revealed that USP3 and SRSF1 specifically interact with RIG-I in vitro ( xref and xref )."
USP3 inhibits RIGI.
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USP3 inhibits RIGI. 7 / 9
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"USP3, USP21, and CYLD suppress RIG-I activation by removing the K63 polyubiquitin chain on the N-terminal CARD of RIG-I [ 19–21 ]."

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"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)."

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"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."

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

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"Both USP3 and USP21 negatively regulate RIG-I activation via the cleavage of Lys63-linked Ubs conjugated on the 2CARD [ 51,52 ]."

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

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"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."
USP3 deubiquitinates RIGI.
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USP3 deubiquitinates RIGI. 3 / 3
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"<span class="match term0">USP3</span> inhibits type I interferon signaling by deubiquitinating <span class="match term1">RIG-I</span>-like receptors"

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"For example, TNFAIP3, CYLD, USP3, USP4, USP15, USP25, and OTUD5 deubiquitinate key components of the IFN production pathway, including RIG-I, TRAF2, TRAF3, TRAF6, RIP1, and TRIF (reviewed in [93,94])."

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"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 activates RIGI.
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USP3 activates RIGI. 2 / 2
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"For example, ubiquitin-specific peptidase 3 (USP3), USP21, and cylindromatosis lysine 63 deubiquitinase (CYLD) modulate RIG-I signaling by removing K63-polyubiquitin chains (Cui et al., 2014; Fan et al., 2014)."

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"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."
MYD88 affects USP3
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MYD88 binds USP3.
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sparser
"USP3 is a key component of the MyD88-USP3 axis, essential for the development of innate immune tolerance [ xref ]."

sparser
"Specifically, using recombinant proteins, we showed that USP3 and MyD88 interacted directly in vitro (Fig  xref )."

sparser
"Our results showed that both USP3 domains could bind to MyD88, but the ZnF domain exhibited a stronger binding ability with MyD88 (Fig  xref )."

sparser
"To determine the physiological relevance of these findings, we stimulated the THP‐1 cells or peripheral blood mononuclear cells (PBMCs) with LPS and found that the interaction between MyD88 and USP3 was induced by LPS treatment and peaked at 60 min after LPS treatment, which correlated with p‐IKK activation (Fig  xref )."

sparser
"Furthermore, to identify the region of USP3 binding to MyD88, we generated two deletion mutants of USP3 containing the zinc‐finger Ub‐binding domain (ZnF‐UBP) (referred to as ZnF) or ubiquitin‐specific protease catalytic domain (UCH)."

sparser
"However, an in vitro binding assay using recombinant MyD88 showed that neither of the individual domains of USP3 could directly interact with non‐ubiquitinated MyD88 purified from E. coli (Fig  xref )."

sparser
"This work identifies a previously unrecognized post‐translational feedback loop in the MyD88USP3 axis, which is critical for inducing normal “tolerance” innate immune memory."

sparser
"This indicates that the intact structure of USP3 is critical for its direct interaction with MyD88, and the interaction between individual domains of USP3 with MyD88 shown in Fig  xref may be attributed to the ubiquitination of MyD88."

sparser
"Next, we tested whether the individual domains of USP3 interact selectively with specific ubiquitinated domains of MyD88."

sparser
"Our results revealed that the ZnF domain of USP3 strongly interacted with both domains of MyD88, while the UCH domain of USP3 interacted with the TIR domain of MyD88 but not the DD domain (Fig  xref )."
MYD88 activates USP3.
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MYD88 activates USP3. 1 / 1
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"Collectively, our works reveal a feedback system mediated by the MyD88USP3 axis, which is essential for the establishment of innate immune tolerance and the maintenance of immune homeostasis."
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"USP3 can accelerate gastric cancer metastasis by enhancing the COL9A3/COL6A5 stability via deubiquitination [48]."

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"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."

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"USP3 acts as a deubiquitinase of Aurora A to promote metastasis of esophageal squamous cell carcinoma [53]."

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

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"The upregulation of USP3 in GC has been found to significantly enhance cell proliferation in vitro and promote metastasis in vivo [36, 37]."

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"And study revealed that USP3 promotes the proliferation and metastasis of esophageal squamous cell carcinoma by stabilizing Aurora A [41]."

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"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."

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

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"Through the deubiquitination of the K143 residue of Aurora A, a serine/threonine kinase associated with centrosomes and mitosis, USP3 promotes invasion and metastasis in ESCC cells."

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"USP3 knockdown induced metastasis was abolished by USP3 3 ' UTR overexpression in CRC cells."
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"These results indicated that the loss of USP3 facilitated tumour progression, while overexpression of the USP3 3 ' UTR inhibited metastasis in CRC cells."

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"The results indicated that USP3 knockdown led to more lung metastases than the control group, highlighting the metastatic suppressive capacity of USP3 in CRC.Similarly, a xenograft mouse model was established by subcutaneously injecting cells with USP3 knockdown in GC research."

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"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."

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"Contrary to the previously described cancers, USP3 is downregulated in CRC, and USP3 deficiency leads to tumor metastasis and poor prognosis which can be inhibited by overexpression of the USP3 3’UTR."
USP3 affects SNAI1
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USP3 deubiquitinates SNAI1.
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USP3 deubiquitinates SNAI1. 9 / 9
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"<span class="match term0">USP3</span> interacts directly with <span class="match term1">Snail</span> and stabilizes <span class="match term1">Snail</span> via deubiquitination"

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"34 Additionally, USP3 mediates the deubiquitylation of Snail1, stabilizing its protein levels."

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"The regulatory mechanism not only relies on the SND1-IT1/miR-1245b-5p/USP3 axis, but SND1-IT1 also recruits DDX54 to stabilize USP3, while USP3 also mediates the deubiquitination of SNAIL1 [40]."

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"Deubiquitinases (DUBs) also play an important role in the regulation of Snail1 protein stability, including USP3, USP11, USP13, DUB3, USP18, USP26, USP27X, USP37, USP47, OTUB1, and PSMD14, that have been shown to facilitate deubiquitination and stabilization of nuclear Snail1 in promoting cell proliferation, migration, and invasion ."

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"USP3 mediates SNAIL1 deubiquitination."

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"The outcome showed that USP3 mediated the deubiquitination of SNAIL1 (Fig. 7F)."

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"To sum up, USP3 mediates SNAIL1 deubiquitination."

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"Moreover, our study suggested that USP3 can mediate the deubiquitination of SNAIL1 for the first time."

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"Besides deubiquitinating Snail, USP3 can stabilize other proteins, such as Aurora A, to enhance cell growth and metastases in cancers such as esophageal squamous cell carcinoma ( Shi et al. 2021 )."
USP3 binds SNAI1.
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sparser
"USP3 interacts directly with Snail and stabilizes Snail via deubiquitination."

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"USP3 interacts directly with Snail and stabilizes Snail via deubiquitination."

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USP3 activates SNAI1.
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USP3 activates SNAI1. 3 / 3
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"Implications : Our study establishes USP3 mediated Snail stabilization as an important mechanism underlying GBM invasion and progression, and provides a rationale for potential therapeutic interventions in the treatment of GBM."

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"The result displayed that, USP3 ablation inhibited SNAIL1 protein degradation (Fig. 7H)."

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"For example, USP3, USP11, and USP29 stimulate EMT in glioblastoma cells, as well as in ovarian or gastric cancer cells, respectively, by stabilizing Snail [80–82] ."
USP3 ubiquitinates SNAI1.
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USP3 leads to the ubiquitination of SNAI1. 1 / 1
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"USP3 mediates the deubiquitination of snail family transcriptional repressor 1 (SNAIL1)."
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"USP3 promotes the proliferation, migration and invasion of OS cells."

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"These results underscore the key role of DNM1L in a USP3-induced enhancement of proliferation, migration, and invasion capacities of GBC cells."

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"Additionally, we demonstrated that USP3 promoted the proliferation, migration and invasion of OS cells."

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"Additionally, USP3 promotes GC cell migration and invasion by positively regulating the EMT process."

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

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"In contrast, overexpression of USP3 promoted cell proliferation, migration, and invasion."

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"Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion ."

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"52 Overall, USP3 primarily functions as a tumor promoter in GC, driving GC cell proliferation, invasion, migration, and the EMT process.Ubiquitin‐specific protease 3 has also been implicated in esophageal squamous cell carcinoma (ESCC)."

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

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"Through the deubiquitination of the K143 residue of Aurora A, a serine/threonine kinase associated with centrosomes and mitosis, USP3 promotes invasion and metastasis in ESCC cells."
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"The absence of USP3 in vitro and in vivo models has been shown to decrease NB cell proliferation, migration, and invasion and inhibit tumor growth (43)."

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"It was unmasked by the result that, the promoted cell migration and invasion caused by SND1-IT1 overexpression was totally reversed by USP3 interference (Fig. 6C)."

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"Through in vitro cell proliferation (Fig. 2C), colony formation (Fig. 2D), migration (Fig. 2E), wound healing (Supplemental Fig. 1C) and invasion (Fig. 2F) assay, we found that downregulation of USP3 inhibited the proliferation, migration and invasion of osteosarcoma cells."

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"Loss of USP3 promotes cell migration and invasion in vitro, along with lung metastasis in vivo, highlighting the antimetastatic capacity of USP3 in CRC."
USP3 affects KLF5
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USP3 binds KLF5.
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sparser
"In breast cancer, Yingying Wu et al. found that the carboxyl-terminal active region of USP3 (residues 111–521aa) binds to the amino-terminal region of KLF5 (residues 1–200aa) to promote KLF5 expression via deubiquitination ( xref )."

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"USP3 can interact with KLF5 and stabilize KLF5 through deubiquitination."

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"We demonstrated that USP3 interacts with KLF5 and stabilizes KLF5 via deubiquitination."

sparser
"We demonstrated that USP3 interacts with KLF5 and stabilizes KLF5 via deubiquitination."

sparser
"Notably, unlike USP3, the active region of USP38 is located at the amino terminus (1-400aa), indicating that although both USP38 and USP3 bind to the same active region of KLF5, the differences in their respective active regions may lead to differential sensitivity in regulating KLF5 expression."

sparser
"USP3 can interact with KLF5 and stabilize KLF5 through deubiquitination."
BAP1 binds USP3 and KLF5. 1 / 1
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"Both BAP1 and USP3 bind to and stabilize KLF5 via deubiquitination [ xref , xref ], indicating the possible regulatory role of DUBs in cancer proliferation."
USP3 deubiquitinates KLF5.
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USP3 deubiquitinates KLF5. 5 / 5
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"USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5."

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"For example, ATXN3L and USP3 mediate the deubiquitination of KLF5 and thus regulate the proliferation of BC cells [39,40]."

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"These findings imply that the UCHL1-KLF5 axis might be a valuable therapeutic target for TNBC.Besides UCHL1, some other DUBs, such as ATXN3L, BAP1, and USP3 can deubiquitinate KLF5 and are implicated in the pathological development of breast cancer [29, 41, 42]."

"We demonstrated that <span class="match term0">USP3</span> interacts with <span class="match term1">KLF5</span> and stabilizes <span class="match term1">KLF5</span> via deubiquitination"

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"For example, USP3 regulates cancer progression and metastasis by deubiquitinating the Kruppel-like factor 5 (KLF5), stabilizing p53 or deubiquitination-dependent COL9A3/COL6A5."
USP3 affects Ubiquitin
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USP3 inhibits Ubiquitin.
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"Sharma et al. revealed that USP3 could eliminate ubiquitin at lysines 13 and 15 of histone H2A and γH2AX, as well as ubiquitin at lysines 118 and 119 of H2AX in response to DNA damage [6]."

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"As shown in Fig. 5e, ectopic USP3 expression decreased ubiquitin and K48-linked ubiquitin that combined with DNM1L protein by the proteasome inhibitor MG132, whereas USP3 knockdown impaired DNM1L deubiquitylation."

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"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."

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"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.
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"As one of the factors responsible for NSCLC cell proliferation, USP3 may lead to Ub-mediated degradation by targeting RBM4, which is a tumour suppressor gene and a key molecule for RNA splicing (79)."

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"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."

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"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."

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"Nagy et al. reported that USP3 promotes neuroblastoma cell viability, proliferation, and xenograft tumor growth by cleaving K48‐ and K63‐linked ubiquitin chains of MYCN (Figure 2C, right)."

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

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"Tight regulation of ubiquitin mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells."
USP3 binds Ubiquitin.
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"Compound 59 Binds the C-Terminal Ubiquitin Binding Site of USP3."

sparser
"Experiments confirmed that mutation of UBP ZnF significantly reduced the interaction of USP3 with ubiquitinated histone uH2A both in vivo and in vitro, suggesting that this is the major domain mediating the interaction between USP3 and ubiquitin [ xref ]."
USP3 affects TRAF6
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USP3 binds TRAF6.
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sparser
"Since USP3 could inhibit IL-1β induced NF-κB activation, and TRAF6 polyubiquitination is critical in the process of IL-1β induced NF-κB activation [ 23 ], we further hypothesized that USP3 could inter[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We provide the first evidence that USP3 binds directly to TRAF6 and inhibits TRAF6 induced NF-κB signaling pathway activation by ubiquitination in a DUB activity-dependent manner."

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sparser
"We provide the first evidence that USP3 binds directly to TRAF6 and inhibits TRAF6 induced NF-κB signaling pathway activation by ubiquitination in a DUB activity-dependent manner."

sparser
"TRAF6 is a key E3 ubiquitin ligase that regulates the NF-κB signaling pathway, and our results prove that USP3 interacts with TRAF6 and regulates TRAF6 ubiuitination by DUB activity, but a variety of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"We found that USP3 interacted with TRAF6 and attenuated the polyubiquitination of TRAF6 induced by IL-1β, thereby negatively regulating NF-κB activation."
USP3 deubiquitinates TRAF6.
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USP3 deubiquitinates TRAF6. 4 / 4
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"We found that USP3 interacted with TRAF6 and attenuated the polyubiquitination of TRAF6 induced by IL-1β, thereby negatively regulating NF-κB activation."

reach
"For example, TNFAIP3, CYLD, USP3, USP4, USP15, USP25, and OTUD5 deubiquitinate key components of the IFN production pathway, including RIG-I, TRAF2, TRAF3, TRAF6, RIP1, and TRIF (reviewed in [93,94])."

reach
"Moreover, USP3 can reverse the ubiquitination of TRAF6 (tumor necrosis factor-receptor-associated factor 6), which intermediates the signals from inflammatory cytokines to NF-κB activation, thus blocking IL-1β-induced chondrocyte apoptosis [27]."

reach
"Meanwhile, USP3 had little effect on the expression of TRAF6, but notably reduced TRAF6 ubiquitination."
USP3 inhibits TRAF6.
| 3
USP3 inhibits TRAF6. 3 / 3
| 3

reach
"Collectively, our results suggest that although USP3 could moderately reduce TRAF6‐induced NF‐κB activation (Zhou et al, 2019), it specifically inhibits TLR‐ and IL‐1β‐induced NF‐κB activation, mainly through the adaptor molecule MyD88.We next sought to determine whether USP3 could interact with MyD88."

reach
"For example, USP3 was deficient in OA and USP3 abundance suppressed IL-1β-induced chondrocyte apoptosis by targeting TRAF6 [6]."

reach
"To identify the molecular target of USP3, we co‐transfected USP3 with different signaling proteins in the NF‐κB pathway and found that USP3 mainly inhibited MyD88‐induced NF‐κB activation and slightly but significantly inhibited TRAF6‐induced NF‐κB activity only at a high USP3 concentration (Fig 3A)."
USP3 ubiquitinates TRAF6.
| 1
USP3 leads to the ubiquitination of TRAF6. 1 / 1
| 1

reach
"IL-1β elevated the ubiquitination of TRAF6, which can be abrogated by overexpression of USP3 in chondrocytes (107)."
USP3 affects SUZ12
2 1 | 3 8
USP3 binds SUZ12.
2 | 1 8
2 | 1 8

sparser
"Therefore, this USP3-SUZ12 axis may contribute to tumor progression, thereby presenting a potential target for therapeutic intervention in human GC ( xref )."

sparser
"To further confirm that USP3 was associated with the SUZ12 protein, we performed reciprocal co-immunoprecipitation experiments using endogenous protein and showed that USP3 can interact with SUZ12 (Fig. xref )."

sparser
"Thus, targeting the USP3-SUZ12 axis may provide a potential therapeutic target for the treatment of GC."

sparser
"The USP3-SUZ12 axis might promote tumor progression and could be a potential therapeutic candidate for human GC."

sparser
"Collectively, these findings suggest that USP3 can physically interact with SUZ12."

sparser
"Taken together, these data suggest that the USP3-SUZ12 axis promotes an EMT-like phenotype in GC cells."

reach
"We observed that USP3 interacted with and stabilized SUZ12 via deubiquitination."

No evidence text available

No evidence text available

sparser
"These findings demonstrate that USP3 is an essential regulator of SUZ12 and that the USP3-SUZ12 signaling axis plays a critical role in the progression and metastasis of GC."
USP3 deubiquitinates SUZ12.
1 | 2
USP3 deubiquitinates SUZ12. 3 / 3
1 | 2

"<span class="match term0">UBIQUITIN-SPECIFIC PROTEASE 3</span> promotes cell migration and invasion by interacting with and deubiquitinating <span class="match term1">SUZ12</span> in gastric cancer"

reach
"USP3 promotes cell migration and invasion by interacting with and deubiquitinating SUZ12 in gastric cancer ( Wu et al., 2019 )."

reach
"Among them, SUZ12, a scaffolding component of the PRC2 complex, and COL9A3/COL6A5, collagen family members, were deubiquitinated and stabilized by USP3, which accounts for its role in promoting invasion and migration [21,22]."
USP3 affects REST
3 | 3 8
USP3 binds REST.
3 | 1 8
3 | 1 8

No evidence text available

sparser
"USP3 interacts with REST."

sparser
"The interaction between USP3 and REST was confirmed by immunoprecipitation and Duolink in situ proximity assays."

sparser
"As a functional consequence of the interaction between USP3 and REST, the half-life of REST protein was extended by the deubiquitinating activity of USP3 (Fig.  xref )."

sparser
"The deubiquitinase USP3 interacts with REST, stabilizing and prolonging the half-life of REST protein, thereby counteracting its ubiquitination in NB ( xref , xref )."

reach
"The interaction between USP3 and REST was confirmed by immunoprecipitation and Duolink in situ proximity assays."

sparser
"An anti-Flag antibody co-immunoprecipitated ectopically expressed Myc-REST along with Flag-USP3 and vice-versa in HEK293 cells (Fig.  xref A), indicating that USP3 interacts with REST."

No evidence text available

No evidence text available

sparser
"Furthermore, Duolink PLA was used to visualize in situ interaction between USP3 and REST using a standard immunofluorescence staining assay."
USP3 increases the amount of REST.
| 1
USP3 increases the amount of REST. 1 / 1
| 1

reach
"USP3, one of the DUBs with the highest expression of USP family genes in neuroblastoma, is positively correlated with REST, a transcriptional repressor in non-neuronal cells and neural stem cells [51], and USP3 promotes tumor formation and growth by stabilizing the level of REST proteins through deubiquitination [52]."
USP3 activates REST.
| 1
USP3 activates REST. 1 / 1
| 1

reach
"We identified a deubiquitinase USP3 that interacts with, stabilizes, and increases the half-life of REST protein by counteracting its ubiquitination in neuroblastoma."
USP3 affects TP53
3 1 | 1 5 3
USP3 binds TP53.
3 | 1 2
3 | 1 2

trips
"Here we report that USP3 interacts with p53 and regulates p53 stability."

sparser
"To further confirm this interaction, we tested whether endogenous USP3 interact with endogenous p53."

sparser
"Fu S and his colleagues have shown that USP3 interacts with p53 and regulates p53 stability and that depletion of USP3 leads to accelerated degradation of p53 in normal cells and therefore enhanced cell proliferation and transformation [ xref ]."

No evidence text available

No evidence text available

No evidence text available
USP3 deubiquitinates TP53.
1 | 3
USP3 deubiquitinates TP53. 4 / 4
1 | 3

reach
"We observed that reconstitution of wildtype USP3 greatly suppressed p53 ubiquitination, while the C168S mutant did not affect p53 ubiquitination level ( Fig. 3 d–e)."

"Depletion of <span class="match term0">USP3</span> lead to accelerated degradation of <span class="match term1">p53</span> in normal cells thereby enhanced cell proliferation and transformation"

reach
"USP3 deubiquitinates and stabilizes p53 and promotes normal cell transformation.U2OS Cells were maintained in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (Gibco, USA), [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"We found that loss of USP3 dramatically enhanced p53 ubiquitination ( Fig. 3 a)."
USP3 activates TP53.
| 2
USP3 activates TP53. 2 / 2
| 2

reach
"We found that overexpression of USP3 greatly suppressed p53 protein degradation comparing to control cells ( Fig. 2 g)."

reach
"These results suggest that USP3 enhances p53 protein stability.Because USP3 stabilizes p53 protein, it is possible that p53 is the substrate of USP3."
USP3 ubiquitinates TP53.
| 1
USP3 ubiquitinates TP53. 1 / 1
| 1

sparser
"We found that loss of USP3 dramatically enhanced p53 ubiquitination ( Fig. 3 a)."
USP3 affects COL6A5
3 | 8 2
USP3 binds COL6A5.
3 | 2 2
3 | 2 2

sparser
"Our experiments revealed that COL9A3 combined with USP3 by its M3 region, and COL6A5 interacted with USP3 through its H2 region (Fig. xref )."

sparser
"This study suggests that targeting of the USP3-COL9A3 or USP3-COL6A5 axis could be developed as a therapeutic strategy for GC management."

reach
"For instance, USP3 can bind and deubiquitinate COL9A3/COL6A5 to facilitate gastric cancer cell migration and progression (Wu et al. 2021)."

No evidence text available

No evidence text available

No evidence text available

reach
"Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC."
USP3 deubiquitinates COL6A5.
| 4
USP3 deubiquitinates COL6A5. 4 / 4
| 4

reach
"Among them, SUZ12, a scaffolding component of the PRC2 complex, and COL9A3/COL6A5, collagen family members, were deubiquitinated and stabilized by USP3, which accounts for its role in promoting invasion and migration [21,22]."

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

reach
"The deubiquitination enzyme USP3, an essential mediator regulating oncogenic activity both in vitro and in vivo, can deubiquitinate COL9A3 and COL6A5 in gastric cancer cells."

reach
"Similarly, USP3 was reported to promote the gastric cancer progression and metastasis by deubiquitinating COL9A3 and COL6A5 [38]."
USP3 activates COL6A5.
| 2
USP3 activates COL6A5. 2 / 2
| 2

reach
"USP3 can accelerate gastric cancer metastasis by enhancing the COL9A3/COL6A5 stability via deubiquitination [48]."

reach
"Additionally, USP3 accelerates gastric cancer development by stabilizing COL9A3/COL6A5 through deubiquitination52."
RIGI affects USP3
2 | 6 5
2 | 6 1

reach
"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63 linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [XREF_BIBR], we focused on SRSF1 for further experiments."

sparser
"Notably, at the resting state, USP3 does not bind RIG-I, and upon viral infection, an induced USP3 binding to RIG-I leads to the removal of K63-linked ubiquitin chains to restrain or terminate RIG-I signaling ( xref )."

No evidence text available

No evidence text available

reach
"USP3 binds RIG-I and removes the K63-polyubiquitin chains on the N-terminal CARDs [XREF_BIBR]."

reach
"Upon virus infection, USP3 interacted with RIG-I, likely acting as a negative feedback regulator."

reach
"We found that USP3 and a splicing-factor oncoprotein, serine/arginine rich splicing factor 1 (SRSF1), interact with RIG-I."

reach
"Coimmunoprecipitation and western blot analyses revealed that USP3 and SRSF1 specifically interact with RIG-I in vitro (XREF_FIG and XREF_SUPPLEMENTARY)."

reach
"Notably, at the resting state, USP3 does not bind RIG-I, and upon viral infection, an induced USP3 binding to RIG-I leads to the removal of K63-linked ubiquitin chains to restrain or terminate RIG-I signaling (133)."
USP3 binds RIGI and IFIH1. 2 / 2
| 2

sparser
"The interaction of USP3 with RIG-I and MDA5 is strictly based upon ligand stimulation."

sparser
"Also co-IP demonstrated the interaction between USP3 and stimulated RIG-I or MDA5, but not the unstimulated ones, supporting that ligand stimulation is required for USP3 to interact with RIG-I or MDA5 [ xref ]."
UBC binds USP3 and RIGI. 1 / 1
| 1

sparser
"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63-linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [ xref ], we focused on SRSF1 for further experiments."
USP3 binds SRSF1 and RIGI. 1 / 1
| 1

sparser
"To examine which proteins directly interact with RIG-I, we transfected 293T cells with HA-tagged candidate genes together with Flag-tagged RIG-I. Coimmunoprecipitation and western blot analyses revealed that USP3 and SRSF1 specifically interact with RIG-I in vitro ( xref and xref )."
USP3 affects SMARCA5
| 10 2
USP3 binds SMARCA5.
| 4 2
USP3 binds SMARCA5 and K63. 4 / 4
| 4

reach
"USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5."

reach
"These data demonstrate that USP3 regulates cellular response to docetaxel in prostate cancer cells in a SMARCA5 dependent manner.Collectively, we reveal that USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance (Fig. 6K)."

reach
"USP3 directly binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."

reach
"Mechanistically, USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5, which enhancing its stability."
| 2

sparser
"Collectively, our findings uncover a novel molecular mechanism for the USP3-SMARCA5 axis in regulating DSB repair with an important role in chemotherapy response in human prostate cancers, highlighting that targeting USP3-SMARCA5 axis could be a valuable strategy to treat USP3/SMARCA5-overexpressing chemotherapy-resistant patients and improve drug treatment."

sparser
"Here, we report that the deubiquitinating enzyme USP3 directly interacts with SMARCA5 and removes K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."
USP3 deubiquitinates SMARCA5.
| 4
USP3 deubiquitinates SMARCA5. 4 / 4
| 4

reach
"Herein, we report one critical target of USP3, SMARCA5 and the specific mechanism of USP3-mediated deubiquitination of SMARCA5 in Docetaxel-inducing DNA damage, suggesting that USP3 may be a promising target for anticancer therapy in prostate cancer.SMARCA5, the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5, was required for DNA-templated events including transcription, DNA replication, and DNA repair [17, 18]."

reach
"Firstly, we found USP3 silencing increased SMARCA5 polyubiquitination (Fig. 3J)."

reach
"Second, ectopic expression of wild-type USP3, but not the C168S mutant, reduced the polyubiquitination of SMARCA5 (Fig. 3K), suggesting that the enzymatic activity of USP3 is indispensable for USP3-dependent deubiquitination of SMARCA5."

reach
"Taken together, these results suggest that USP3 targets SMARCA5 for stability.As USP3 and SMARCA5 were required for DNA repair [18, 22], which has a key role in human cancer, it is possible that USP3 promotes deubiquitination and stabilization of SMARCA5 in PCa specimens."
USP3 inhibits SMARCA5.
| 2
USP3 inhibits SMARCA5. 2 / 2
| 2

reach
"Depletion of USP3 or SMARCA5 promoted PCa cells sensitive to docetaxel and overexpression of USP3 restored the cells resistance to docetaxel treatment in SMARCA5 silenced cells."

reach
"Depletion of USP3 or SMARCA5 promoted PCa cells sensitive to docetaxel and overexpression of USP3 restored the cells resistance to docetaxel treatment in SMARCA5 silenced cells in vitro and vivo."
USP3 affects DNM1L
| 7 5
USP3 binds DNM1L.
| 2 5
| 2 5

sparser
"These findings suggested that the USP3-DNM1L interaction mediated the function of GBC cells."

sparser
"Therefore, we speculated that G_DYNAMIN_2 might be an important domain for DNM1L to bind to USP3."

sparser
"Collectively, USP3 stabilizes DNM1L through deubiquitination, thereby remodeling mitochondrial dynamics and cellular metabolism, providing a theoretical basis and experimental foundation for precision therapies targeting the USP3DNM1L axis in GBC ( xref )."

reach
"The immunoprecipitated samples was eluted using an elution buffer and subsequently analyzed via western blot assay.To verify the domains of DNM1L binds to USP3, various HA-tagged DNM1L deletion mutants (including HA-1–302 aa, HA-303–643 aa, and HA-644–736 aa) or HA-full constructs (HA-1–736 aa) and Flag-USP3 constructs were generated in the pcDNA3.1 vector."

reach
"USP3 physically interacted with and stabilized DNM1L."

sparser
"These findings suggest that the USP3DNM1L axis drives the malignant phenotype of gallbladder cancer via the “mitochondrial dynamics-metabolic reprogramming-tumor progression” pathway, providing a theoretical basis for therapeutic strategies targeting mitochondrial metabolism."

sparser
"USP3 binds the GTPase domain (1–302 aa) of DNM1L and selectively cleaves K48-linked ubiquitin chains, prolonging DNM1L half-life and promoting its induction of excessive mitochondrial fission, ATP depletion, reactive oxygen species (ROS) accumulation, and mitochondrial DNA (mtDNA) loss."
USP3 deubiquitinates DNM1L.
| 2
USP3 deubiquitinates DNM1L. 2 / 2
| 2

reach
"It predicted that USP3 possibly deubiquitinated DNM1L through the ubiquitylation sites for substrate protein."

reach
"Deubiquitination of DNM1L by USP3 triggers the development and metastasis of gallbladder carcinoma."
USP3 inhibits DNM1L.
| 1
USP3 inhibits DNM1L. 1 / 1
| 1

reach
"We discovered that USP3 overexpression was associated with a significantly extended DNM1L half-life after treatment with CHX, and USP3 downregulation accelerated the protein degradation of DNM1L (Fig. 5d)."
USP3 increases the amount of DNM1L.
| 1
USP3 increases the amount of DNM1L. 1 / 1
| 1

reach
"Inversely, USP3 positively regulated the DNM1L protein level (Fig. 5b)."
USP3 activates DNM1L.
| 1
USP3 activates DNM1L. 1 / 1
| 1

reach
"To detail, overexpression of USP3 increased DNM1L stability by inhibiting the K48-like ubiquitination of DNM1L (Fig. 5d-e)."
USP3 affects COL9A3
3 | 8 1
USP3 binds COL9A3.
3 | 2 1
3 | 2 1

No evidence text available

sparser
"This study suggests that targeting of the USP3-COL9A3 or USP3-COL6A5 axis could be developed as a therapeutic strategy for GC management."

reach
"For instance, USP3 can bind and deubiquitinate COL9A3/COL6A5 to facilitate gastric cancer cell migration and progression (Wu et al. 2021)."

No evidence text available

No evidence text available

reach
"Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC."
USP3 deubiquitinates COL9A3.
| 4
USP3 deubiquitinates COL9A3. 4 / 4
| 4

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

reach
"Among them, SUZ12, a scaffolding component of the PRC2 complex, and COL9A3/COL6A5, collagen family members, were deubiquitinated and stabilized by USP3, which accounts for its role in promoting invasion and migration [21,22]."

reach
"The deubiquitination enzyme USP3, an essential mediator regulating oncogenic activity both in vitro and in vivo, can deubiquitinate COL9A3 and COL6A5 in gastric cancer cells."

reach
"Similarly, USP3 was reported to promote the gastric cancer progression and metastasis by deubiquitinating COL9A3 and COL6A5 [38]."
USP3 activates COL9A3.
| 2
USP3 activates COL9A3. 2 / 2
| 2

reach
"Additionally, USP3 accelerates gastric cancer development by stabilizing COL9A3/COL6A5 through deubiquitination52."

reach
"USP3 can accelerate gastric cancer metastasis by enhancing the COL9A3/COL6A5 stability via deubiquitination [48]."
USP3 affects CHEK1
4 1 | 4 3
USP3 binds CHEK1.
4 | 2 3
4 | 2 3

sparser
"The interaction between USP3 and CHK1 results in the direct removal of the inhibitory ubiquitin chain at K63, leading to the release of CHK1 from chromatin and subsequent down-regulation of USP3, which enhances gene stability [ xref ]."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

reach
"32 Additionally, a study has revealed that USP3 interacts with checkpoint kinase 1 (CHK1), counteracting the effects of BTG3‐mediated K63‐linked polyubiquitination of CHK1."

reach
"However, after phosphorylation of CHK1 at Ser-345 a deubiquitinase, USP3, associates with CHK1 on the chromatin and removes the ubiquitin chain thereby facilitating chromatin dissociation and accessib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Additionally, a study has revealed that USP3 interacts with checkpoint kinase 1 (CHK1), counteracting the effects of BTG3‐mediated K63‐linked polyubiquitination of CHK1. xref This interaction turns off CHK1 phosphorylation and activation by upstream kinases, facilitating CHK1 release from chromatin to exert its kinase activity on other substrates."

sparser
"However, after phosphorylation of CHK1 at Ser-345 a deubiquitinase, USP3, associates with CHK1 on the chromatin and removes the ubiquitin chain thereby facilitating chromatin dissociation and accessib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 deubiquitinates CHEK1.
1 | 1
USP3 leads to the deubiquitination of CHEK1. 2 / 2
1 | 1

"Herein, we show that the K63-linked ubiquitin chain at <span class="match term1">CHK1</span>'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 (<span class="match term0">USP3</span>), a deubiquitinating enzyme that targets K63-linked ubiquitin chains."

reach
"Multiple ubiquitin ligases, including the SKP1-CUL1-F-box (SCF) complex, CUL4-DDB1, and HUWE1 [ 89–93 ] can target CHK1 for proteasomal degradation, whereas the deubiquitinases USP1, USP3, USP7, and A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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."
REST affects USP3
3 | 1 8
3 | 1 8

No evidence text available

sparser
"USP3 interacts with REST."

sparser
"The interaction between USP3 and REST was confirmed by immunoprecipitation and Duolink in situ proximity assays."

sparser
"As a functional consequence of the interaction between USP3 and REST, the half-life of REST protein was extended by the deubiquitinating activity of USP3 (Fig.  xref )."

sparser
"The deubiquitinase USP3 interacts with REST, stabilizing and prolonging the half-life of REST protein, thereby counteracting its ubiquitination in NB ( xref , xref )."

reach
"The interaction between USP3 and REST was confirmed by immunoprecipitation and Duolink in situ proximity assays."

sparser
"An anti-Flag antibody co-immunoprecipitated ectopically expressed Myc-REST along with Flag-USP3 and vice-versa in HEK293 cells (Fig.  xref A), indicating that USP3 interacts with REST."

No evidence text available

No evidence text available

sparser
"Furthermore, Duolink PLA was used to visualize in situ interaction between USP3 and REST using a standard immunofluorescence staining assay."
USP3 affects IFIH1
2 | 4 5
USP3 binds IFIH1.
2 | 1 5
2 | 1 1

sparser
"In addition, viral infection induces USP3 interaction with MDA5 to catalyze the removal of K63-linked ubiquitin chains, thus limiting sustained activation of MDA5 signaling ( xref )."

No evidence text available

reach
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [XREF_BIBR]."

No evidence text available
USP3 binds RIGI and IFIH1. 2 / 2
| 2

sparser
"The interaction of USP3 with RIG-I and MDA5 is strictly based upon ligand stimulation."

sparser
"Also co-IP demonstrated the interaction between USP3 and stimulated RIG-I or MDA5, but not the unstimulated ones, supporting that ligand stimulation is required for USP3 to interact with RIG-I or MDA5 [ xref ]."
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
USP3 binds polyubiquitin and IFIH1. 1 / 1
| 1

sparser
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [ xref ]."
USP3 inhibits IFIH1.
| 3
USP3 inhibits IFIH1. 3 / 3
| 3

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."

reach
"In addition, ubiquitin-specific protease 3 (USP3), a deubiquitinase, was reported to bind to MDA5, remove K63-polyubiquitin chains on the N-terminal CARDs, and then inhibit MDA5 activity [168]."
USP3 affects Histone
| 9 2
USP3 deubiquitinates Histone.
| 5
USP3 deubiquitinates Histone-H2A. 3 / 3
| 3

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

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
"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 deubiquitinates Histone. 2 / 2
| 2

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 ubiquitinates Histone.
| 2
USP3 leads to the ubiquitination of Histone on K13. 1 / 1
| 1

reach
"Irradiated USP3-knockdown cells showed prolonged accumulation of ubiquitinated histone H2A (Mosbech et al., 2013; Nicassio et al., 2007), while over-expression of a wild type but not catalytically ina[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 leads to the ubiquitination of Histone on K15. 1 / 1
| 1

reach
"Irradiated USP3-knockdown cells showed prolonged accumulation of ubiquitinated histone H2A (Mosbech et al., 2013; Nicassio et al., 2007), while over-expression of a wild type but not catalytically ina[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 decreases the amount of Histone.
| 2
USP3 decreases the amount of ubiquitinated Histone. 2 / 2
| 2

reach
"USP3 activity reduces the global levels of monoubiquitinated histones important for transcriptional activation, such as histone H2B monoubiquitination at K120 (H2BK120ub)."

reach
"Increased USP3 activity reduces global levels of monoubiquitinated histones including histone H2A and H2B monoubiquitination at K119 and K120 (H2AmUb and H2BmUb, respectively)."
USP3 binds Histone.
| 2
| 2

sparser
"USP3 does in fact interact with ubiquitinated H2A-type histones, and mouse embryonic fibroblasts isolated from USP3-null mice express increased levels of ubiquitinated H2A [ xref ]."

sparser
"Experiments confirmed that mutation of UBP ZnF significantly reduced the interaction of USP3 with ubiquitinated histone uH2A both in vivo and in vitro, suggesting that this is the major domain mediating the interaction between USP3 and ubiquitin [ xref ]."
SUZ12 affects USP3
2 | 1 8
2 | 1 8

sparser
"Therefore, this USP3-SUZ12 axis may contribute to tumor progression, thereby presenting a potential target for therapeutic intervention in human GC ( xref )."

sparser
"To further confirm that USP3 was associated with the SUZ12 protein, we performed reciprocal co-immunoprecipitation experiments using endogenous protein and showed that USP3 can interact with SUZ12 (Fig. xref )."

sparser
"Thus, targeting the USP3-SUZ12 axis may provide a potential therapeutic target for the treatment of GC."

sparser
"The USP3-SUZ12 axis might promote tumor progression and could be a potential therapeutic candidate for human GC."

sparser
"Collectively, these findings suggest that USP3 can physically interact with SUZ12."

sparser
"Taken together, these data suggest that the USP3-SUZ12 axis promotes an EMT-like phenotype in GC cells."

reach
"We observed that USP3 interacted with and stabilized SUZ12 via deubiquitination."

No evidence text available

No evidence text available

sparser
"These findings demonstrate that USP3 is an essential regulator of SUZ12 and that the USP3-SUZ12 signaling axis plays a critical role in the progression and metastasis of GC."
USP3 affects WDTC1
2 | 5 3
USP3 binds WDTC1.
2 | 3
2 | 3

sparser
"The results of Co-IP assay confirmed that USP3 and WDTC1 can endogenously interact with each other (Fig.  xref C)."

sparser
"GST pull-down assay further verified that USP3 and WDTC1 can directly interact with each other (Fig.  xref D)."

sparser
"Furthermore, we confirmed that USP3 and WDTC1 can interact endogenously and directly."

No evidence text available

No evidence text available
USP3 increases the amount of WDTC1.
| 2
USP3 increases the amount of WDTC1. 2 / 2
| 2

reach
"WDTC1 expression was increased by USP3, while WDTC1 and USP3 expression can be increased by ELF5."

reach
"We then observed that USP3 overexpression significantly upregulated WDTC1 protein levels in cells by western blot (Fig. 7E)."
USP3 activates WDTC1.
| 2
USP3 activates WDTC1. 2 / 2
| 2

reach
"ELF5 promotes USP3-mediated WDTC1 stabilization."

reach
"ELF5 can promote USP3-mediated WDTC1 stabilization."
USP3 deubiquitinates WDTC1.
| 1
USP3 leads to the deubiquitination of WDTC1. 1 / 1
| 1

reach
"Moreover, USP3 inhibited WDTC1 ubiquitination."
| 3 7
USP3 activates Stomach Neoplasms.
| 3 6
| 3 6

reach
"However, it is unknown whether these three proteins are involved in the USP3-directed proliferation of GC cells, and future studies should examine their oncogenic roles in GC."

reach
"49 Their findings indicate that USP3 overexpression accelerates GC cell proliferation by promoting G1–S transition and upregulating cyclins D and E."

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
"Additionally, USP3 promotes GC cell migration and invasion by positively regulating the EMT process."

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

reach
"52 Overall, USP3 primarily functions as a tumor promoter in GC, driving GC cell proliferation, invasion, migration, and the EMT process.Ubiquitin‐specific protease 3 has also been implicated in esophageal squamous cell carcinoma (ESCC)."

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

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

reach
"According to the literature review, USP3 promotes GC cell migration and invasion [20]; SLC7A6 hasn’t been reported in studies related to cancer; IGF2BP1 accelerates GC progression [21]; and TKT facilitates breast cancer metastasis [22]."
| 1

reach
"Our investigation also found that USP3 overexpression suppressed GC cell migration and proliferation, suggesting that USP3 was a miR-224-5p downstream target.In summary, we identified that hsa_circ_00[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 affects POU5F1
2 | 1 7
2 | 1 7

sparser
"USP3 interacts with endogenous Oct4 and co-localizes in the nucleus of hESCs."

sparser
"USP3 Interacted with Oct4."

sparser
"For this purpose, we performed immunoprecipitation (IP) experiments to investigate the interaction between USP3 and Oct4 at the exogenous level."

reach
"USP3 interacts with endogenous Oct4 and co-localizes in the nucleus of hESCs."

sparser
"USP3 interacted with Oct4 and co-localized in cell nucleus of embryonic stem cells."

sparser
"IP using endogenous USP3 antibody resulted in precipitation of endogenous Oct4 in NCCIT cells ( xref C) as well as in hiPSCs ( xref D), indicating that USP3 interacts stably with endogenous Oct4 in stem cells."

sparser
"Furthermore, we demonstrated that USP3 and Oct4 interact regardless of whether Oct4 is endogenously or exogenously expressed and co-localize in the nuclei of hESCs ( xref )."

sparser
"Thus, the interaction between USP3 and Oct4 is critical for maintenance of the pluripotency of hESCs."

No evidence text available

No evidence text available
USP3 affects Neoplasms
| 1 8
| 1 8

reach
"Functional studies further demonstrated that USP3 promotes osteosarcoma cell proliferation and tumor growth both in vitro and in vivo."

reach
"USP3, as a deubiquitinating enzyme, mediates tumor progression mainly by deubiquitinating and modifying downstream target proteins."

reach
"Additionally, Wu et al. constructed a USP3 knockdown xenograft tumor model of breast cancer, demonstrating that a decrease in USP3 significantly inhibited tumor growth compared with the control group."

reach
"USP3 knockdown inhibited tumor growth, while co-overexpression of SMARCA5 significantly rescued this effect (Fig. 5E–G)."

reach
"Depletion of USP3 significantly represses mouse xenograft tumor growth."

reach
"As shown in Fig. 6G–I, depletion of USP3 or docetaxel treatment similarly inhibited tumor growth, whereas the combined silencing of USP3 and docetaxel treatment did further reduce tumor growth in the xenograft model."

reach
"Additionally, overexpressed USP3 significantly promoted cell proliferation in vitro and tumor growth in vivo, while the silencing of USP3 inhibited proliferation and tumor growth."

reach
"Nagy et al. reported that USP3 promotes neuroblastoma cell viability, proliferation, and xenograft tumor growth by cleaving K48‐ and K63‐linked ubiquitin chains of MYCN (Figure 2C, right)."

eidos
"Our previous study revealed that USP3 promotes tumour progression and is highly expressed in gastric cancer ( GC ) ."
USP3 affects Interferon
| 10
USP3 inhibits Interferon.
| 7
| 7

reach
"USP3 was reported to deubiquitinate RIG-1-like receptors, and inhibits type I interferon signaling [10] ."

reach
"USP3 specifically negatively regulates type I IFN signaling by removal of the K63-linked polyubiquitin chains from RIG-I ( Cui et al., 2014 )."

reach
"USP3 negatively regulates the activation of type 1 interferon (IFN-I) signaling by specifically targeting Retinoic acid-inducible gene I lysine 63(RIG-I K63)-linked polyubiquitin chains and removing them, resulting in IFN-I inhibition."

reach
"USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors."

reach
"For example, USP3 and CYLD were reported to negatively regulate type I IFN induction by targeting RIG-I ( Cui et al., 2014 ; Friedman et al., 2008 ); OTUD1 potently inhibits innate antiviral immunity [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"However, the ZnF domain of USP3 alone cannot inhibit RIG-I-induced type I IFN activation, and the UCH domain may require ZnF for maximal catalytic activity, suggesting that both intact ZnF and the catalytic domain are required for USP3 to exert its deubiquitination function [11]."

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."
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 deubiquitinates Interferon.
| 1
USP3 deubiquitinates Interferon. 1 / 1
| 1

reach
"For example, TNFAIP3, CYLD, USP3, USP4, USP15, USP25, and OTUD5 deubiquitinate key components of the IFN production pathway, including RIG-I, TRAF2, TRAF3, TRAF6, RIP1, and TRIF (reviewed in [93,94])."
USP3 activates Interferon.
| 1
| 1

reach
"USP3 modulates the type I IFN response by specifically binding to the CARD domains of RIG-I and MDA5, thereby inhibiting their activation."
USP3 affects Histone_H2B
| 10
USP3 deubiquitinates Histone_H2B.
| 9
USP3 deubiquitinates Histone_H2B. 7 / 7
| 7

reach
"Exogenous USP3 deubiquitinates H2A and H2B ( Nicassio et al., 2007 ) and overexpression of USP16 and USP44 reverses RNF8/RNF168-mediated ubiquitination ( Mosbech et al., 2013; Shanbhag et al., 2010 )."

reach
"USP3 that was found as chromatin associated DUB suppresses global mono-ubiquitylation of H2A (and also H2B)."

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

reach
"The involvement of USP3 in DDR was first reported in 2007 by Nicassio et al. 32 According to their findings, USP3 is essential for the complete deubiquitylation of uH2A/H2B and γ‐H2AX through its enzymatic catalytic activity."

reach
"Usp3 can deubiquitinate both H2A and H2B in humans."

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

reach
"In the DDR, USP3 dynamically interacts with chromatin and deubiquitinates H2A and H2B."
USP3 leads to the deubiquitination of Histone_H2B on K119. 1 / 1
| 1

reach
"Increased USP3 activity reduces global levels of monoubiquitinated histones including histone H2A and H2B monoubiquitination at K119 and K120 (H2AmUb and H2BmUb, respectively)."
USP3 leads to the deubiquitination of Histone_H2B on K120. 1 / 1
| 1

reach
"Increased USP3 activity reduces global levels of monoubiquitinated histones including histone H2A and H2B monoubiquitination at K119 and K120 (H2AmUb and H2BmUb, respectively)."
USP3 binds Histone_H2B.
| 1

reach
"In the DDR, USP3 dynamically interacts with chromatin and deubiquitinates H2A and H2B."
USP3 affects Flag
| 10
| 10

sparser
"To determine the functional consequence of the deubiquitinating activity of USP3 on REST protein turnover, we treated cells with the protein synthesis inhibitor cycloheximide (CHX) in the presence of Flag-USP3 or catalytic mutant Flag-USP3CS."

sparser
"To determine differentially expressed proteins that may serve as potential interaction targets of USP3, total protein extracted from the treated BGC-823 cells stably expressing the Flag-USP3 fusion protein and the BGC-823 cells carrying an empty vector was analyzed using iTRAQ experiments."

sparser
"Moreover, knockdown of USP3 showed a significant reduction in the half-life of REST protein (Fig.  xref G, lanes 5–8), which was then rescued by reconstitution with Flag-USP3 (Fig.  xref G, lanes 9–12) but not with Flag-USP3CS (Fig.  xref H, lanes 9–12)."

sparser
"Similarly, in HEK293 cells, we observed protein stabilization of ectopically expressed Myc-Oct4 as the concentration of Flag-USP3 increased ( xref E), but expression of the catalytic mutant Flag-USP3CS had no such stabilization effect ( xref F)."

sparser
"We co-transfected Flag-USP3 and Myc-Oct4 into HEK293 cells and performed IP with Flag or Myc antibodies, followed by Western blot with reciprocal antibodies."

sparser
"An anti-Flag antibody co-immunoprecipitated ectopically expressed Myc-REST along with Flag-USP3 and vice-versa in HEK293 cells (Fig.  xref A), indicating that USP3 interacts with REST."

sparser
"Flag-USP3 co-precipitated Myc-Oct4 ( xref A), and similarly Myc-Oct4 co-precipitated Flag-USP3 ( xref B)."

sparser
"To validate whether USP3 could increase the REST protein levels, we transfected the neuroblastoma cells with an increasing concentration of Flag-USP3 and catalytic mutant Flag-USP3CS."

sparser
"The increasing concentration of Flag-USP3 showed an increase in endogenous REST protein levels in a dose-dependent manner (Fig.  xref D)."

sparser
"Moreover, the reduced endogenous expression of the REST protein level in USP3-depleted cells was rescued by reconstitution with Flag-USP3 (Fig.  xref J, lane 4 vs. 3)."
USP3 affects EPHA2
| 8 2
USP3 binds EPHA2.
| 2 2
| 1 2

reach
"USP3 leads to activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2, then reducing protein degradation."

sparser
"USP3 binds to and deubiquitinates EPHA2."

sparser
"Moreover, R203 of USP3 was important during the interaction between USP3 and EPHA2, and K882 and K945 of EPHA2 were the key ubiquitination sites regulated by USP3."
USP3 binds EPHA2 and K882. 1 / 1
| 1

reach
"Moreover, R203 of USP3 was important during the interaction between USP3 and EPHA2, and K882 and K945 of EPHA2 were the key ubiquitination sites regulated by USP3."
USP3 deubiquitinates EPHA2.
| 2
USP3 deubiquitinates EPHA2. 2 / 2
| 2

reach
"Further protein quantification analysis revealed that the half-life of EPHA2 was approximately 6 h. USP3 binds to and deubiquitinates EPHA2."

reach
"In this study, we identified the downstream substrate of USP3, EPHA2, through ubiquitin-omics sequencing and found that USP3 can deubiquitinating EPHA2 and regulate its stability."
USP3 activates EPHA2.
| 2
USP3 activates EPHA2. 2 / 2
| 2

reach
"In additional, we also found that overexpression of USP3 led to a decrease in the ubiquitination level of EPHA2 protein (Fig. 5A), whereas knockdown of USP3 promoted degradation of EPHA2 through ubiquitination (Fig. 5B)."

reach
"Mechanistically, USP3 activated PI3K/AKT signaling pathway through binding to EPHA2 and then reducing its protein degradation."
USP3 inhibits EPHA2.
| 1
USP3 inhibits EPHA2. 1 / 1
| 1

reach
"The results showed that the upregulation of USP3 inhibited the degradation of EPHA2 protein, whereas the downregulation of USP3 promoted its degradation (Fig. 3F)."
USP3 increases the amount of EPHA2.
| 1
USP3 increases the amount of EPHA2. 1 / 1
| 1

reach
"In additional, we also found that overexpression of USP3 led to a decrease in the ubiquitination level of EPHA2 protein (Fig. 5A), whereas knockdown of USP3 promoted degradation of EPHA2 through ubiquitination (Fig. 5B)."
SNAI1 affects USP3
6 | 3 1
SNAI1 binds USP3.
6 | 1 1
6 | 1 1

No evidence text available

No evidence text available

sparser
"USP3 interacts directly with Snail and stabilizes Snail via deubiquitination."

reach
"USP3 interacts directly with Snail and stabilizes Snail via deubiquitination."

No evidence text available

No evidence text available

No evidence text available

No evidence text available
SNAI1 inhibits USP3.
| 1
SNAI1 inhibits USP3. 1 / 1
| 1

reach
"Ectopic expression of Snail could largely rescue the inhibitory effects of USP3 depletion on migration, invasion and tumor growth of GBM cells."
SNAI1 increases the amount of USP3.
| 1
Unubiquitinated SNAI1 increases the amount of USP3. 1 / 1
| 1

reach
"Lastly, SND1-IT1 is significantly overexpressed in GC cell-secreted exosomes and promotes malignant transformation of GES-1 by increasing USP3 expression and mediating deubiquitination of SNAIL1 (Jin et al., 2022)."
POU5F1 affects USP3
2 | 1 7
2 | 1 7

sparser
"USP3 interacts with endogenous Oct4 and co-localizes in the nucleus of hESCs."

sparser
"USP3 Interacted with Oct4."

sparser
"For this purpose, we performed immunoprecipitation (IP) experiments to investigate the interaction between USP3 and Oct4 at the exogenous level."

reach
"USP3 interacts with endogenous Oct4 and co-localizes in the nucleus of hESCs."

sparser
"USP3 interacted with Oct4 and co-localized in cell nucleus of embryonic stem cells."

sparser
"IP using endogenous USP3 antibody resulted in precipitation of endogenous Oct4 in NCCIT cells ( xref C) as well as in hiPSCs ( xref D), indicating that USP3 interacts stably with endogenous Oct4 in stem cells."

sparser
"Furthermore, we demonstrated that USP3 and Oct4 interact regardless of whether Oct4 is endogenously or exogenously expressed and co-localize in the nuclei of hESCs ( xref )."

sparser
"Thus, the interaction between USP3 and Oct4 is critical for maintenance of the pluripotency of hESCs."

No evidence text available

No evidence text available
KLF5 affects USP3
3 | 2 5
3 | 2 4

sparser
"In breast cancer, Yingying Wu et al. found that the carboxyl-terminal active region of USP3 (residues 111–521aa) binds to the amino-terminal region of KLF5 (residues 1–200aa) to promote KLF5 expression via deubiquitination ( xref )."

reach
"USP3 can interact with KLF5 and stabilize KLF5 through deubiquitination."

No evidence text available

No evidence text available

No evidence text available

reach
"We demonstrated that USP3 interacts with KLF5 and stabilizes KLF5 via deubiquitination."

sparser
"We demonstrated that USP3 interacts with KLF5 and stabilizes KLF5 via deubiquitination."

sparser
"Notably, unlike USP3, the active region of USP38 is located at the amino terminus (1-400aa), indicating that although both USP38 and USP3 bind to the same active region of KLF5, the differences in their respective active regions may lead to differential sensitivity in regulating KLF5 expression."

sparser
"USP3 can interact with KLF5 and stabilize KLF5 through deubiquitination."
BAP1 binds USP3 and KLF5. 1 / 1
| 1

sparser
"Both BAP1 and USP3 bind to and stabilize KLF5 via deubiquitination [ xref , xref ], indicating the possible regulatory role of DUBs in cancer proliferation."
Flag affects USP3
| 10
| 10

sparser
"To determine the functional consequence of the deubiquitinating activity of USP3 on REST protein turnover, we treated cells with the protein synthesis inhibitor cycloheximide (CHX) in the presence of Flag-USP3 or catalytic mutant Flag-USP3CS."

sparser
"To determine differentially expressed proteins that may serve as potential interaction targets of USP3, total protein extracted from the treated BGC-823 cells stably expressing the Flag-USP3 fusion protein and the BGC-823 cells carrying an empty vector was analyzed using iTRAQ experiments."

sparser
"Moreover, knockdown of USP3 showed a significant reduction in the half-life of REST protein (Fig.  xref G, lanes 5–8), which was then rescued by reconstitution with Flag-USP3 (Fig.  xref G, lanes 9–12) but not with Flag-USP3CS (Fig.  xref H, lanes 9–12)."

sparser
"Similarly, in HEK293 cells, we observed protein stabilization of ectopically expressed Myc-Oct4 as the concentration of Flag-USP3 increased ( xref E), but expression of the catalytic mutant Flag-USP3CS had no such stabilization effect ( xref F)."

sparser
"We co-transfected Flag-USP3 and Myc-Oct4 into HEK293 cells and performed IP with Flag or Myc antibodies, followed by Western blot with reciprocal antibodies."

sparser
"An anti-Flag antibody co-immunoprecipitated ectopically expressed Myc-REST along with Flag-USP3 and vice-versa in HEK293 cells (Fig.  xref A), indicating that USP3 interacts with REST."

sparser
"Flag-USP3 co-precipitated Myc-Oct4 ( xref A), and similarly Myc-Oct4 co-precipitated Flag-USP3 ( xref B)."

sparser
"To validate whether USP3 could increase the REST protein levels, we transfected the neuroblastoma cells with an increasing concentration of Flag-USP3 and catalytic mutant Flag-USP3CS."

sparser
"The increasing concentration of Flag-USP3 showed an increase in endogenous REST protein levels in a dose-dependent manner (Fig.  xref D)."

sparser
"Moreover, the reduced endogenous expression of the REST protein level in USP3-depleted cells was rescued by reconstitution with Flag-USP3 (Fig.  xref J, lane 4 vs. 3)."
USP3 affects UBC
8 | 1
8 |

No evidence text available

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UBC binds USP3 and RIGI. 1 / 1
| 1

sparser
"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63-linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [ xref ], we focused on SRSF1 for further experiments."
USP3 affects RNF168
| 7
USP3 inhibits RNF168. 7 / 9
| 7

reach
"USP3: Antagonizing RNF8/RNF168 at H2A-Type Histones."

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
"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
"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
"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
"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
"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 H2AC20
1 | 6 2
USP3 deubiquitinates H2AC20.
1 | 3
USP3 deubiquitinates H2AC20. 4 / 4
1 | 3

reach
"USP3 dynamically associates with chromatin and deubiquitylates uH2A/uH2B in vivo ."

"<span class="match term0">USP3</span> counteracts RNF168 via deubiquitinating H2A and gammaH2AX at lysine 13 and 15"

reach
"The involvement of USP3 in DDR was first reported in 2007 by Nicassio et al. 32 According to their findings, USP3 is essential for the complete deubiquitylation of uH2A/H2B and γ‐H2AX through its enzymatic catalytic activity."

reach
"Further studies revealed that in addition to uH2A, USP3 also deubiquitinates conjugate Ub-γH2AX (variant H2A) at K13-15."
USP3 binds H2AC20.
| 2
| 1

sparser
"Based on its zinc-finger Ub-binding domain (ZnF-UBP) and a catalytic domain of the Ub-specific protease (USP) class, the ZnF-UBP domain of USP3 mediates monoubiquitinated H2A (uH2A)-USP3 interaction, which affected DNA damage response [ xref ]."
| 1

sparser
"Both USP3 and USP16 are also associated with H2A deubiquitination following DNA damage processing [ xref , xref ]."
USP3 activates H2AC20.
| 2
USP3 activates H2AC20. 2 / 2
| 2

reach
"Based on its zinc-finger Ub-binding domain (ZnF-UBP) and a catalytic domain of the Ub-specific protease (USP) class, the ZnF-UBP domain of USP3 mediates monoubiquitinated H2A (uH2A)-USP3 interaction, which affected DNA damage response [26]."

reach
"The ZnF-UBP domain of USP3 mediates uH2AUSP3 interaction and USP3 inhibition leads to a delay in S phase progression and to accumulation of DNA breaks."
USP3 increases the amount of H2AC20.
| 1
USP3 increases the amount of H2AC20. 1 / 1
| 1

reach
"The downregulation of USP3 significantly elevates uH2A and uH2B protein levels, leading to functional consequences such as replication stress, abnormal DNA replication and/or recombination, delayed S‐phase progression, accumulation of DNA breaks, and hyperactivation of ATR/ATM‐regulated checkpoint responses."
UBC affects USP3
8 | 1
8 |

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UBC binds USP3 and RIGI. 1 / 1
| 1

sparser
"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63-linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [ xref ], we focused on SRSF1 for further experiments."
IFIH1 affects USP3
2 | 2 5
IFIH1 binds USP3.
2 | 1 5
2 | 1 1

sparser
"In addition, viral infection induces USP3 interaction with MDA5 to catalyze the removal of K63-linked ubiquitin chains, thus limiting sustained activation of MDA5 signaling ( xref )."

No evidence text available

reach
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [XREF_BIBR]."

No evidence text available
USP3 binds RIGI and IFIH1. 2 / 2
| 2

sparser
"The interaction of USP3 with RIG-I and MDA5 is strictly based upon ligand stimulation."

sparser
"Also co-IP demonstrated the interaction between USP3 and stimulated RIG-I or MDA5, but not the unstimulated ones, supporting that ligand stimulation is required for USP3 to interact with RIG-I or MDA5 [ xref ]."
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
USP3 binds polyubiquitin and IFIH1. 1 / 1
| 1

sparser
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [ xref ]."
IFIH1 inhibits USP3.
| 1
IFIH1 inhibits USP3. 1 / 1
| 1

reach
"Notably, USP3 was shown to directly bind the MDA5 CARDs and inhibited signaling by the constitutively active, truncated form of MDA5 (N-MDA5)."
ELF5 affects USP3
| 7 2
ELF5 activates USP3.
| 3 2
ELF5 activates USP3. 5 / 5
| 3 2

sparser
"ELF5 transcriptionally activates USP3."

sparser
"These results confirmed that ELF5 transcriptionally activated USP3 in RCC."

reach
"ELF5 transcriptionally activates USP3."

reach
"The luciferase reporter assay manifested that ELF5 overexpression obviously elevated the luciferase activity of the USP3 promoter."

reach
"These results confirmed that ELF5 transcriptionally activated USP3 in RCC."
ELF5 increases the amount of USP3.
| 4
ELF5 increases the amount of USP3. 4 / 4
| 4

reach
"WDTC1 expression was increased by USP3, while WDTC1 and USP3 expression can be increased by ELF5."

reach
"Next, we observed ELF5 overexpression could effectively enhance the mRNA and protein levels of USP3 in 769-P and A498 cells (Fig. 6E-F)."

reach
"Further, ELF5 overexpression was found to upregulate USP3 and WDTC1 levels (Fig. 7F)."

reach
"As a result, only USP3 expression was notably upregulated by ELF5 overexpression (Fig. 6D)."
CHEK1 affects USP3
4 | 2 3
4 | 2 3

sparser
"The interaction between USP3 and CHK1 results in the direct removal of the inhibitory ubiquitin chain at K63, leading to the release of CHK1 from chromatin and subsequent down-regulation of USP3, which enhances gene stability [ xref ]."

No evidence text available

No evidence text available

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reach
"32 Additionally, a study has revealed that USP3 interacts with checkpoint kinase 1 (CHK1), counteracting the effects of BTG3‐mediated K63‐linked polyubiquitination of CHK1."

reach
"However, after phosphorylation of CHK1 at Ser-345 a deubiquitinase, USP3, associates with CHK1 on the chromatin and removes the ubiquitin chain thereby facilitating chromatin dissociation and accessib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Additionally, a study has revealed that USP3 interacts with checkpoint kinase 1 (CHK1), counteracting the effects of BTG3‐mediated K63‐linked polyubiquitination of CHK1. xref This interaction turns off CHK1 phosphorylation and activation by upstream kinases, facilitating CHK1 release from chromatin to exert its kinase activity on other substrates."

sparser
"However, after phosphorylation of CHK1 at Ser-345 a deubiquitinase, USP3, associates with CHK1 on the chromatin and removes the ubiquitin chain thereby facilitating chromatin dissociation and accessib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Additionally, USP3 promotes GC cell migration and invasion by positively regulating the EMT process."

reach
"52 Overall, USP3 primarily functions as a tumor promoter in GC, driving GC cell proliferation, invasion, migration, and the EMT process.Ubiquitin‐specific protease 3 has also been implicated in esophageal squamous cell carcinoma (ESCC)."

reach
"In GBM, the transcription factor Snail plays a crucial role in USP3-mediated EMT, promoting cell invasion, migration, and tumor progression [45]."

reach
"For example, USP3, USP11, and USP29 stimulate EMT in glioblastoma cells, as well as in ovarian or gastric cancer cells, respectively, by stabilizing Snail [80–82] ."

reach
"Previous studies have shown that USP3 raised GBM progression by regulating EMT."

reach
"However, USP3 has been demonstrated to promote EMT and tumourigenesis in glioblastoma in vitro and in vivo ( Fan et al. 2019 )."

reach
"27 , 28 Recent studies have proven that USP3 promotes GBM progress by regulating the EMT process."

reach
"Moreover, TGF-beta1 induced USP3 expression, and USP3 knockdown inhibited TGF-beta1-induced EMT."
USP3 affects MYCN
1 | 6 1
USP3 deubiquitinates MYCN.
1 | 1
USP3 leads to the deubiquitination of MYCN. 2 / 2
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

"We show that increased <span class="match term0">USP3</span> levels reduce K-48- and K-63-linked ubiquitination of <span class="match term1">MYCN</span>, thus driving up <span class="match term1">MYCN</span> protein stability"
USP3 decreases the amount of MYCN.
| 2
USP3 decreases the amount of MYCN. 2 / 2
| 2

reach
"Further studies revealed that in vitro experiments and in vivo transgenic models of NBL displayed the formation of a nuclear co-activator complex between ALYREF and MYCN that stimulates the transcript[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"As shown in Figure S7, ablation of CCNB1IP1 partially prevented the upregulation of MYCN protein level in Trim32 or Huwe1 knockdown cells, and overexpression of CCNB1IP1 differentially attenuated the downregulation of MYCN protein level caused by USP3 or USP5 silencing."
USP3 binds MYCN.
| 1 1
| 1

sparser
"USP3 interacts directly with its protein targets, which prompted us to examine whether MYCN also bound USP3 directly."
ALYREF binds USP3 and MYCN. 1 / 1
| 1

reach
"The ALYREF-USP3-MYCN complex is a potential therapeutic target for NB by exploiting obligatory ALYREF dependence in MYCN-amplified cells [37]."
USP3 activates MYCN.
| 2
USP3 activates MYCN. 2 / 2
| 2

reach
"ALYREF and MYCN form a transcriptional activator complex, which upregulates USP3 expression, promoting the growth and tumorigenicity of MYCN-amplified neuroblastoma cells [24]."

reach
"Nagy et al. reported that USP3 promotes neuroblastoma cell viability, proliferation, and xenograft tumor growth by cleaving K48‐ and K63‐linked ubiquitin chains of MYCN (Figure 2C, right)."
USP3 affects IFNB1
| 8
USP3 inhibits IFNB1.
| 5
USP3 inhibits IFNB1. 5 / 5
| 5

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
"Cellular ubiquitin-specific proteases, USP21 ( Fan et al., 2014 ), USP3 ( Cui et al., 2014 ) and USP15 ( Zhang et al., 2015 ), a subfamily of deubiqutinase ( Reyes-Turcu et al., 2009 ), remove K63-lin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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
"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."

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."
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."
COL6A5 affects USP3
3 | 3 2
COL6A5 binds USP3.
3 | 2 2
3 | 2 2

sparser
"Our experiments revealed that COL9A3 combined with USP3 by its M3 region, and COL6A5 interacted with USP3 through its H2 region (Fig. xref )."

sparser
"This study suggests that targeting of the USP3-COL9A3 or USP3-COL6A5 axis could be developed as a therapeutic strategy for GC management."

reach
"For instance, USP3 can bind and deubiquitinate COL9A3/COL6A5 to facilitate gastric cancer cell migration and progression (Wu et al. 2021)."

No evidence text available

No evidence text available

No evidence text available

reach
"Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC."
COL6A5 activates USP3.
| 1
COL6A5 activates USP3. 1 / 1
| 1

reach
"Importantly, we found that COL9A3 and COL6A5 were essential mediators of USP3-modulated oncogenic activity in vitro and in vivo."
| 7
USP3 activates cell migration.
| 4
| 4

reach
"Additionally, USP3 promotes GC cell migration and invasion by positively regulating the EMT process."

reach
"It was shown that cell migration was promoted by SND1-IT1 up-regulation, and was then totally reversed by USP3 inhibition (Fig. 6A)."

reach
"According to the literature review, USP3 promotes GC cell migration and invasion [20]; SLC7A6 hasn’t been reported in studies related to cancer; IGF2BP1 accelerates GC progression [21]; and TKT facilitates breast cancer metastasis [22]."

reach
"As shown in Fig. 6a-c, USP3 overexpression significantly promoted cell migration and invasion compared to empty vector-transfected cells, whereas Dox-induced DNM1L silencing suppressed the capabilities."
USP3 inhibits cell migration.
| 3

reach
"Loss of USP3 promotes cell migration and invasion in vitro, along with lung metastasis in vivo, highlighting the antimetastatic capacity of USP3 in CRC."

reach
"It was unmasked by the result that, the promoted cell migration and invasion caused by SND1-IT1 overexpression was totally reversed by USP3 interference (Fig. 6C)."

reach
"Our investigation also found that USP3 overexpression suppressed GC cell migration and proliferation, suggesting that USP3 was a miR-224-5p downstream target.In summary, we identified that hsa_circ_00[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 affects USP3
| 7
USP3 increases the amount of USP3.
| 3
USP3 increases the amount of USP3. 3 / 3
| 3

reach
"Results of the rescue assay confirmed that PKLR knockdown suppressed USP3-induced oncogenic activity in USP3 overexpressed GBC cells."

reach
"Western blot and real-time PCR proved that USP3 specific siRNA could significantly knockdown USP3 expression level ( Fig. 3 A and B)."

reach
"RT-qPCR also showed that miR-224-5p overexpression decreased USP3 expression, while overexpression of USP3 increased USP3 expression ( Fig. 5 C, D)."
USP3 activates USP3.
| 2
USP3 activates USP3. 2 / 2
| 2

reach
"Although we observed the existence of cytoplasmic USP3 even without LPS stimulation in USP3‐expressing THP‐1 cells, possibly due to the overexpression of USP3, LPS pretreatment still increased the amount of cytoplasmic USP3 in these cells (Fig EV5C), indicating that LPS‐pretreatment induces the cytoplasmic retention of both endogenous and exogenous USP3 in THP‐1 cells."

reach
"miR-224-5p downregulation or USP3 overexpression significantly increased USP3 ( Fig. 4 E, F), confirming that USP3 was downstream of miR-224-5p."
USP3 inhibits USP3.
| 1
USP3 inhibits USP3. 1 / 1
| 1

reach
"Loss of USP3 promotes cell migration and invasion in vitro, along with lung metastasis in vivo, highlighting the antimetastatic capacity of USP3 in CRC."
USP3 decreases the amount of USP3.
| 1
USP3 decreases the amount of USP3. 1 / 1
| 1

reach
"These data suggested that USP3 overexpression could inhibit IL-1β induced osteoarthritis effects in rat chondrocytes.In order to confirm what we found in USP3 overexpression experiments, 3 different U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 affects SMAD4
| 1 6
USP3 increases the amount of SMAD4.
| 4
USP3 increases the amount of SMAD4. 4 / 4
| 4

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

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

reach
"USP3 modulates SMAD4 expression at the post-transcriptional level."

reach
"Silencing USP3 reduced SMAD4 expression in LoVo and HCT116 cells[71]."
USP3 binds SMAD4.
| 2
| 2

reach
"We utilized luciferase reporter constructs of PGL3-USP3 3 ' UTR and PGL3-SMAD4 3 ' UTR to evaluate whether the interaction between USP3 and SMAD4 was 3 ' UTR dependent."

reach
"This reversal was partially due to the ceRNA interaction between USP3 and SMAD4."
USP3 activates SMAD4.
| 1
USP3 activates SMAD4. 1 / 1
| 1

eidos
"Wang et al. demonstrated that USP3 upregulated SMAD4 by competitively binding miR-224 , thereby inhibiting CRC cell metastasis [ 24 ] ."
USP3 affects MYC
1 | 3 3
USP3 binds MYC.
1 | 1 3
1 | 1 3

sparser
"As shown in Fig. 1 a, Myc-USP3 interacted with p53 specially, but not the control immunoprecipitates."

No evidence text available

sparser
"The elevated USP3 protein then interacted with MYC and promoted its stability by deubiquitination."

sparser
"Additionally, co-immunoprecipitation assays demonstrated an interaction between USP3 and MYC, with subsequent ubiquitination assays showing that USP3 regulates MYC stability."

reach
"Additionally, co-immunoprecipitation assays demonstrated an interaction between USP3 and MYC, with subsequent ubiquitination assays showing that USP3 regulates MYC stability."
USP3 activates MYC.
| 2
USP3 activates MYC. 2 / 2
| 2

reach
"These findings suggest that USP3 modulates ccRCC progression by stabilizing MYC, highlighting its potential as a therapeutic target in ccRCC treatment."

reach
"USP3 promotes clear cell renal cell carcinoma progression by stabilizing MYC and enhancing glycolysis."
TP53 affects USP3
1 3 | 1 2
TP53 binds USP3.
3 | 1 2
3 | 1 2

trips
"Here we report that USP3 interacts with p53 and regulates p53 stability."

sparser
"To further confirm this interaction, we tested whether endogenous USP3 interact with endogenous p53."

sparser
"Fu S and his colleagues have shown that USP3 interacts with p53 and regulates p53 stability and that depletion of USP3 leads to accelerated degradation of p53 in normal cells and therefore enhanced cell proliferation and transformation [ xref ]."

No evidence text available

No evidence text available

No evidence text available
TP53 decreases the amount of USP3.
1 |
TP53 decreases the amount of USP3. 1 / 1
1 |

No evidence text available
SMARCA5 affects USP3
| 5 2
SMARCA5 binds USP3.
| 4 2
USP3 binds SMARCA5 and K63. 4 / 4
| 4

reach
"USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5."

reach
"These data demonstrate that USP3 regulates cellular response to docetaxel in prostate cancer cells in a SMARCA5 dependent manner.Collectively, we reveal that USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance (Fig. 6K)."

reach
"USP3 directly binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."

reach
"Mechanistically, USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5, which enhancing its stability."
| 2

sparser
"Collectively, our findings uncover a novel molecular mechanism for the USP3-SMARCA5 axis in regulating DSB repair with an important role in chemotherapy response in human prostate cancers, highlighting that targeting USP3-SMARCA5 axis could be a valuable strategy to treat USP3/SMARCA5-overexpressing chemotherapy-resistant patients and improve drug treatment."

sparser
"Here, we report that the deubiquitinating enzyme USP3 directly interacts with SMARCA5 and removes K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."
SMARCA5 increases the amount of USP3.
| 1
SMARCA5 increases the amount of USP3. 1 / 1
| 1

reach
"Besides, we demonstrated that SMARCA5 knockdown decreased cell proliferation and significantly rescued the effect of overexpression of USP3 (Fig. 5D)."
JUN affects USP3
7 |
JUN decreases the amount of USP3. 7 / 7
7 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
DNM1L affects USP3
| 2 5
| 2 5

sparser
"These findings suggested that the USP3-DNM1L interaction mediated the function of GBC cells."

sparser
"Therefore, we speculated that G_DYNAMIN_2 might be an important domain for DNM1L to bind to USP3."

sparser
"Collectively, USP3 stabilizes DNM1L through deubiquitination, thereby remodeling mitochondrial dynamics and cellular metabolism, providing a theoretical basis and experimental foundation for precision therapies targeting the USP3DNM1L axis in GBC ( xref )."

reach
"The immunoprecipitated samples was eluted using an elution buffer and subsequently analyzed via western blot assay.To verify the domains of DNM1L binds to USP3, various HA-tagged DNM1L deletion mutants (including HA-1–302 aa, HA-303–643 aa, and HA-644–736 aa) or HA-full constructs (HA-1–736 aa) and Flag-USP3 constructs were generated in the pcDNA3.1 vector."

reach
"USP3 physically interacted with and stabilized DNM1L."

sparser
"These findings suggest that the USP3DNM1L axis drives the malignant phenotype of gallbladder cancer via the “mitochondrial dynamics-metabolic reprogramming-tumor progression” pathway, providing a theoretical basis for therapeutic strategies targeting mitochondrial metabolism."

sparser
"USP3 binds the GTPase domain (1–302 aa) of DNM1L and selectively cleaves K48-linked ubiquitin chains, prolonging DNM1L half-life and promoting its induction of excessive mitochondrial fission, ATP depletion, reactive oxygen species (ROS) accumulation, and mitochondrial DNA (mtDNA) loss."
COL9A3 affects USP3
3 | 3 1
COL9A3 binds USP3.
3 | 2 1
3 | 2 1

No evidence text available

sparser
"This study suggests that targeting of the USP3-COL9A3 or USP3-COL6A5 axis could be developed as a therapeutic strategy for GC management."

reach
"For instance, USP3 can bind and deubiquitinate COL9A3/COL6A5 to facilitate gastric cancer cell migration and progression (Wu et al. 2021)."

No evidence text available

No evidence text available

reach
"Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC."
COL9A3 activates USP3.
| 1
COL9A3 activates USP3. 1 / 1
| 1

reach
"Importantly, we found that COL9A3 and COL6A5 were essential mediators of USP3-modulated oncogenic activity in vitro and in vivo."
| 3 3
USP3 translocates from the nucleus to the cytoplasm. 4 / 4
| 2 2

reach
"Importantly, USP3 was exported from the nucleus to the cytoplasm when p65, but not STAT1, translocated to the nucleus (Fig EV4B)."

reach
"These results suggest that the translocation of USP3 from the nucleus to the cytoplasm is an essential step in its function of removing the K63‐Ub chains on MyD88."

sparser
"Interestingly, we found that GFP‐USP3 translocated from the nucleus to the cytoplasm in HeLa/TLR4 cells upon LPS stimulation (Figs  xref and xref )."

sparser
"Importantly, USP3 was exported from the nucleus to the cytoplasm when p65, but not STAT1, translocated to the nucleus (Fig  xref )."
USP3 translocates to the cytoplasm. 2 / 2
| 1 1

sparser
"Next, we analyzed the cell fractionation of the cytoplasm and nucleus to determine whether endogenous USP3 could also translocate to the cytoplasm after TLR‐induced NF‐κB activation."

reach
"Next, we analyzed the cell fractionation of the cytoplasm and nucleus to determine whether endogenous USP3 could also translocate to the cytoplasm after TLR‐induced NF‐κB activation."
USP3 affects proteolysis
| 6
USP3 activates proteolysis.
| 4
| 4

reach
"Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation."

reach
"Experiments found that the knockdown of USP3 promoted the protein degradation of AR (Fig. 6J)."

reach
"Mechanistically, USP3 activated PI3K/AKT signaling pathway through binding to EPHA2 and then reducing its protein degradation."

reach
"The result displayed that, USP3 ablation inhibited SNAIL1 protein degradation (Fig. 7H)."
USP3 inhibits proteolysis.
| 2
| 2

reach
"We found that overexpression of USP3 greatly suppressed p53 protein degradation comparing to control cells ( Fig. 2 g)."

reach
"We discovered that USP3 overexpression was associated with a significantly extended DNM1L half-life after treatment with CHX, and USP3 downregulation accelerated the protein degradation of DNM1L (Fig. 5d)."
USP3 affects NFASC
| 6
USP3 inhibits NFASC. 6 / 6
| 6

reach
"To identify the molecular target of USP3, we co‐transfected USP3 with different signaling proteins in the NF‐κB pathway and found that USP3 mainly inhibited MyD88‐induced NF‐κB activation and slightly but significantly inhibited TRAF6‐induced NF‐κB activity only at a high USP3 concentration (Fig 3A)."

reach
"Using the USP3 and USP3 cells, we found that USP3 deficiency enhanced the NF‐κB activation induced by MyD88 and TRAF6, but not by IKKα or IKKβ (Fig 3C)."

reach
"Ectopic expression of USP3 inhibited the NF‐κB activation induced by MyD88 in USP3 cells (Fig 3D)."

reach
"LPS priming resulted in the cytoplasmic retention of USP3, which enabled it to remove the K63‐linked polyubiquitin chains more efficiently on MyD88 and attenuate subsequent NF‐κB signaling upon a second LPS challenge."

reach
"Using USP3‐transfected cells treated with IL‐1β (a ligand for IL‐1R), TNFα (a ligand for TNFR), or 293T‐TLR4 cells treated with LPS (a ligand for TLR4), we showed that USP3 potently inhibited the NF‐κB activation induced by LPS and IL‐1β (Fig 1B)."

reach
"To determine whether USP3 could inhibit different types of TLRs‐mediated NF‐κB activation, we tested the secretion of NF‐κB‐responsive cytokines after stimulation with different TLR ligands: Pam CSK (a ligand for TLR1/2), LPS, and CL‐097 (a ligand for TLR7/8)."
USP3 affects IL1
| 6
USP3 inhibits IL1. 6 / 6
| 6

reach
"For example, USP3 was deficient in OA and USP3 abundance suppressed IL-1β-induced chondrocyte apoptosis by targeting TRAF6 [6]."

reach
"USP3 upregulation attenuated IL-1β-mediated apoptosis of chondrocytes and inactivation of NF-κB pathway (107)."

reach
"Our results show that overexpression of USP3 could inhibits IL-1β-induced apoptosis, indicating that USP3 may be a negative regulator of OA development."

reach
"This study demonstrated that USP3 probably attenuated IL-1β-mediated chondrocyte senescence by deacetylating FOXO3 via SIRT3."

reach
"USP3 participates in the establishment of innate immune “tolerance” memory through a non-transcriptional feedback mechanism and negatively regulates TLR/IL1β-induced inflammatory signaling activation by specifically removing the K63-linked polyubiquitin chain on MyD88."

reach
"Ubiquitin-specific protease-3 (USP-3) attenuates IL-1β-mediated chondrocyte senescence by deacetylating forkhead box O-3 via SIRT3 (61)."
USP3 affects CLSPN
1 | 5
USP3 deubiquitinates CLSPN.
1 | 3
USP3 deubiquitinates CLSPN. 4 / 4
1 | 3

"Moreover, we found that Smo reduced <span class="match term1">Claspin</span> polyubiquitination and proteasomal degradation by promoting <span class="match term0">USP3</span> transcription"

reach
"USP3 mediates the deubiquitination of claspin and leads to the successive activation of claspin-dependent ATR–CHK1 signaling, thus enhancing the radiation resistance of glioblastoma (GBM) significantl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Notably, this study finds that this effect is dependent on Claspin polyubiquitination and proteasomal degradation, which can be reduced by USP3 transcription, resulting in regulation of ATR-Chk1 signaling [18]."

reach
"Tu et al. reported that USP3 deubiquitinates Claspin, thus activating ATR-Chk1 signaling in tumor resistance to radiation23."
USP3 ubiquitinates CLSPN.
| 1
USP3 leads to the ubiquitination of CLSPN. 1 / 1
| 1

reach
"Moreover, increased USP3 transcriptionally modulated by Smoothened (Smo) reduces Claspin polyubiquitination and proteasomal degradation, leading to activation of Claspin-dependent ATR-CHK1 signaling and radiation resistance of glioblastoma (GBM) [115]."
USP3 inhibits CLSPN.
| 1
USP3 inhibits CLSPN. 1 / 1
| 1

reach
"Claspin plays a crucial role in the activation of the ATR‐CHK1 signal, and USP3 attenuates the degradation of Claspin by deubiquitinating the K48‐linked polyubiquitination."
TRAF6 affects USP3
1 | 1 4
1 | 1 4

sparser
"Since USP3 could inhibit IL-1β induced NF-κB activation, and TRAF6 polyubiquitination is critical in the process of IL-1β induced NF-κB activation [ 23 ], we further hypothesized that USP3 could inter[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"We provide the first evidence that USP3 binds directly to TRAF6 and inhibits TRAF6 induced NF-κB signaling pathway activation by ubiquitination in a DUB activity-dependent manner."

No evidence text available

sparser
"We provide the first evidence that USP3 binds directly to TRAF6 and inhibits TRAF6 induced NF-κB signaling pathway activation by ubiquitination in a DUB activity-dependent manner."

sparser
"TRAF6 is a key E3 ubiquitin ligase that regulates the NF-κB signaling pathway, and our results prove that USP3 interacts with TRAF6 and regulates TRAF6 ubiuitination by DUB activity, but a variety of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"We found that USP3 interacted with TRAF6 and attenuated the polyubiquitination of TRAF6 induced by IL-1β, thereby negatively regulating NF-κB activation."
EPHA2 affects USP3
| 4 2
EPHA2 binds USP3.
| 2 2
| 1 2

reach
"USP3 leads to activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2, then reducing protein degradation."

sparser
"USP3 binds to and deubiquitinates EPHA2."

sparser
"Moreover, R203 of USP3 was important during the interaction between USP3 and EPHA2, and K882 and K945 of EPHA2 were the key ubiquitination sites regulated by USP3."
USP3 binds EPHA2 and K882. 1 / 1
| 1

reach
"Moreover, R203 of USP3 was important during the interaction between USP3 and EPHA2, and K882 and K945 of EPHA2 were the key ubiquitination sites regulated by USP3."
EPHA2 activates USP3.
| 2
EPHA2 activates USP3. 2 / 2
| 2

reach
"And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating."

reach
"The knockdown of EPHA2 in 143B cells inhibited the activation of the PI3K/AKT signaling pathway and partially reversed the activation of USP3 in this signaling pathway (Fig. 6A)."
| 5

reach
"Since nucleus exportation is a prerequisite step for USP3 to target MyD88 and inhibit NF‐κB signaling activation, we hypothesized that LPS priming could result in the retention of USP3 in the cytoplasm."

reach
"Consistently, LPS priming resulted in the cytoplasmic retention of USP3 in control THP‐1 cells (Fig EV5C)."

reach
"Although we observed the existence of cytoplasmic USP3 even without LPS stimulation in USP3‐expressing THP‐1 cells, possibly due to the overexpression of USP3, LPS pretreatment still increased the amount of cytoplasmic USP3 in these cells (Fig EV5C), indicating that LPS‐pretreatment induces the cytoplasmic retention of both endogenous and exogenous USP3 in THP‐1 cells."

reach
"LPS priming resulted in the cytoplasmic retention of USP3, which enabled it to remove the K63‐linked polyubiquitin chains more efficiently on MyD88 and attenuate subsequent NF‐κB signaling upon a second LPS challenge."

reach
"At the same time, LPS pretreatment can induce the cytoplasmic retention of USP3 and a rapid and intense transfer to the cytoplasm upon a second LPS challenge, which allows USP3 to rapidly shut down NF-κB signaling [77]."
WDTC1 affects USP3
2 | 3
2 | 3

sparser
"The results of Co-IP assay confirmed that USP3 and WDTC1 can endogenously interact with each other (Fig.  xref C)."

sparser
"GST pull-down assay further verified that USP3 and WDTC1 can directly interact with each other (Fig.  xref D)."

sparser
"Furthermore, we confirmed that USP3 and WDTC1 can interact endogenously and directly."

No evidence text available

No evidence text available
USP3 affects TP53BP1
1 | 4
USP3 inhibits TP53BP1.
| 4
USP3 inhibits TP53BP1. 4 / 4
| 4

reach
"53BP1 and RAP80 foci are also negatively regulated by USP3 catalytic activity [18,110,132,135,136]."

reach
"Overexpression of USP3 and USP44 suppresses the localization of 53BP1 to the damage site."

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."

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."
USP3 binds TP53BP1.
1 |
1 |

No evidence text available
USP3 affects PKLR
1 | 2 2
USP3 binds PKLR.
1 | 2
1 | 2

sparser
"These findings imply that USP3 is an essential positive regulator in GBC progression, and USP3-PKLR plays a vital role in the progression and metabolism of GBC."

No evidence text available

sparser
"These findings imply that USP3 is an essential positive regulator in GBC progression, and USP3-PKLR plays a vital role in the progression and metabolism of GBC."
USP3 increases the amount of PKLR.
| 1
USP3 increases the amount of PKLR. 1 / 1
| 1

reach
"USP3 promotes gallbladder cancer proliferation by modifying the deubiquitination level of pyruvate kinase L/R [37], and USP3 facilitates breast cancer progression through KLF5 deubiquitination [38]."
USP3 deubiquitinates PKLR.
| 1
USP3 deubiquitinates PKLR. 1 / 1
| 1

reach
"53 In gallbladder cancer, Liang et al. reported that USP3 deubiquitinates and stabilizes PKLR, a critical regulator of glycolysis."
USP3 affects K63
| 4 1
USP3 binds SMARCA5 and K63. 4 / 4
| 4

reach
"USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5."

reach
"These data demonstrate that USP3 regulates cellular response to docetaxel in prostate cancer cells in a SMARCA5 dependent manner.Collectively, we reveal that USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance (Fig. 6K)."

reach
"USP3 directly binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."

reach
"Mechanistically, USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5, which enhancing its stability."
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
USP3 affects IRF3
| 1 3 1
USP3 inhibits IRF3.
| 1 1
USP3 inhibits IRF3. 2 / 2
| 1 1

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 ]."
USP3 phosphorylates IRF3.
| 1
USP3 leads to the phosphorylation of IRF3. 1 / 1
| 1

reach
"Knockdown of USP3 specifically enhanced K63 linked ubiquitination of RIG-I, upregulated the phosphorylation of IRF3 and augmented the production of type I interferon cytokines and antiviral immunity."
USP3 dephosphorylates IRF3.
| 1
USP3 leads to the dephosphorylation of IRF3. 1 / 1
| 1

reach
"Conversely, the silencing of USP3 enhanced the phosphorylation of IRF3 and IFN-beta protein expression under similar conditions."
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."
USP3 affects H2AX
1 | 4
USP3 deubiquitinates H2AX. 5 / 5
1 | 4

reach
"Further studies revealed that in addition to uH2A, USP3 also deubiquitinates conjugate Ub-γH2AX (variant H2A) at K13-15."

reach
"USP3, USP51 and USP16 de-ubiquitinate H2A/H2AX with varying degrees of specificity [47–49]."

reach
"In addition, USP3 deubiquitinates histone H2A and H2AX, negatively regulating the recruitment of DNA damage repair proteins ."

reach
"During DNA damage repair, USP3 negatively regulates the accumulation of BRCA1 and 53BP1 at DNA break sites by deubiquitinating Ub-conjugates of γH2AX (Ub-γH2AX) and uH2A [26]."
USP3 affects Circulin-C
| 5

sparser
"The results showed that circ-CCDC66, circ-ABCC1, circ-STIL and circ-USP3 could effectively be transcribed by random 6-mer but not oligo (dT) primers ( Fig. 1 D), which indicated that these circRNAs ha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Taken together, these results suggest that circ-CCDC66, circ-ABCC1, circ-STIL and circ-USP3 are stable in the plasma of CRC patients."

sparser
"We excluded circ-USP3 from further consideration because no significant difference was found for plasma levels of this marker in the CRC patients vs . the healthy controls."

sparser
"We selected circ-CCDC66 (chr3:56626997-56628056) [22] , circ-ABCC1 (chr16:16101672-16162159) [23] , circ-STIL (chr1:47745912-47748131) [24] and circ-USP3 (chr15:63824845-63855207) [11] for further inv[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The results showed that circ-CCDC66, circ-ABCC1, circ-STIL and circ-USP3 could be amplified by divergent primers and were resistant to RNase R digestion ( Fig. 1 A–B)."
| 5
| 5

reach
"In control mice, injection of PC3 cells resulted in formation of large prostate tumors, while comparable injection of PC3 cells transduced with either one of two different USP3 shRNAs indicated that USP3 knockdown decreased tumorigenesis (Fig. 2H–J)."

reach
"In neuroblastoma patients, the m C reader ALYREF forms a nuclear coactivator complex with MYCN to stimulate USP3 transcription, which promotes the tumorigenesis of neuroblastoma (89)."

reach
"Suppression of USP3 blocked breast cancer cell tumorigenesis in vivo and proliferation in vitro ( Wu et al., 2019d ) ( Table 1 )."

reach
"USP3 knockdown inhibits subcutaneous tumorigenesis and distant lung metastasis in vivo."

reach
"Elevated USP3 levels further increase MYCN protein levels, contributing to neuroblastoma tumorigenesis."
MYC affects USP3
1 | 1 3
1 | 1 3

sparser
"As shown in Fig. 1 a, Myc-USP3 interacted with p53 specially, but not the control immunoprecipitates."

No evidence text available

sparser
"The elevated USP3 protein then interacted with MYC and promoted its stability by deubiquitination."

sparser
"Additionally, co-immunoprecipitation assays demonstrated an interaction between USP3 and MYC, with subsequent ubiquitination assays showing that USP3 regulates MYC stability."

reach
"Additionally, co-immunoprecipitation assays demonstrated an interaction between USP3 and MYC, with subsequent ubiquitination assays showing that USP3 regulates MYC stability."
K63 affects USP3
| 4 1
USP3 binds SMARCA5 and K63. 4 / 4
| 4

reach
"USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5."

reach
"These data demonstrate that USP3 regulates cellular response to docetaxel in prostate cancer cells in a SMARCA5 dependent manner.Collectively, we reveal that USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance (Fig. 6K)."

reach
"USP3 directly binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."

reach
"Mechanistically, USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5, which enhancing its stability."
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
Circulin-C affects USP3
| 5

sparser
"The results showed that circ-CCDC66, circ-ABCC1, circ-STIL and circ-USP3 could effectively be transcribed by random 6-mer but not oligo (dT) primers ( Fig. 1 D), which indicated that these circRNAs ha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Taken together, these results suggest that circ-CCDC66, circ-ABCC1, circ-STIL and circ-USP3 are stable in the plasma of CRC patients."

sparser
"We excluded circ-USP3 from further consideration because no significant difference was found for plasma levels of this marker in the CRC patients vs . the healthy controls."

sparser
"We selected circ-CCDC66 (chr3:56626997-56628056) [22] , circ-ABCC1 (chr16:16101672-16162159) [23] , circ-STIL (chr1:47745912-47748131) [24] and circ-USP3 (chr15:63824845-63855207) [11] for further inv[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The results showed that circ-CCDC66, circ-ABCC1, circ-STIL and circ-USP3 could be amplified by divergent primers and were resistant to RNase R digestion ( Fig. 1 A–B)."
4 |
Pirinixic acid increases the amount of USP3.
2 |
Pirinixic acid increases the amount of USP3. 2 / 2
2 |

No evidence text available

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

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

No evidence text available
| 4

reach
"USP3 promotes clear cell renal cell carcinoma progression by stabilizing MYC and enhancing glycolysis."

reach
"Glycolysis in GBC cells ws promoted by the USP3 overexpression and inhibited bye USP3 downregulation."

reach
"It promotes cell proliferation, invasion, migration, DNA damage repair, and glycolysis, potentially via the Wnt/β-catenin signaling pathway.14 Similarly, USP3 promotes cholangiocarcinoma proliferation and invasion through the Wnt/MYC pathway, enhancing tumor cell glycolysis, energy production, and upregulating metabolic target genes such as GLUT1, HK2, PDM2, and LDHA.87 Egfr/Stat3."

reach
"Among them, SIRT3 exerts anti-cancer effects by inhibiting the Warburg effect, while FGFR2 fusion, FEN1, and USP3 promote aerobic glycolysis through the activation of NF-κB and Wnt pathways."
USP3 affects PYCARD
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
| 4
| 4

reach
"Nagy et al. reported that USP3 promotes neuroblastoma cell viability, proliferation, and xenograft tumor growth by cleaving K48‐ and K63‐linked ubiquitin chains of MYCN (Figure 2C, right)."

reach
"In neuroblastoma patients, the m C reader ALYREF forms a nuclear coactivator complex with MYCN to stimulate USP3 transcription, which promotes the tumorigenesis of neuroblastoma (89)."

reach
"Furthermore, the activation of USP3 induces neuroblastoma [35]."

reach
"ALYREF and MYCN form a transcriptional activator complex, which upregulates USP3 expression, promoting the growth and tumorigenicity of MYCN-amplified neuroblastoma cells [24]."
USP3 affects MAVS
| 1 2 1
USP3 inhibits MAVS. 4 / 4
| 1 2 1

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

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

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

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

reach
"And study revealed that USP3 promotes the proliferation and metastasis of esophageal squamous cell carcinoma by stabilizing Aurora A [41]."

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

reach
"USP3 acts as a deubiquitinase of Aurora A to promote metastasis of esophageal squamous cell carcinoma [53]."

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."
USP3 affects DDR
| 4
USP3 activates DDR. 4 / 4
| 4

reach
"Overall, despite the non-specificity towards H2A ubiquitination [74], current data support the notion that USP3, at least in part, counteracts the RNF168-mediated pathway in regulating the DDR."

reach
"Knockdown of USP3 impairs the DDR through SMARCA5 and results in increased sensitivity to Docetaxel treatment in prostate cancer cells."

reach
"38 Conversely, Das et al. report that the upregulation of USP3 stimulates the DDR, evident from a substantial increase in γ‐H2AX following USP3 overexpression."

reach
"Isolation of USP3 interacting partners and potential additional substrates, as well as addressing if and how USP3 is regulated, is needed to gain a better understanding of the molecular mechanism of USP3 mediated DDR."
USP3 affects CDC25A
2 1 | 1
USP3 binds CDC25A.
2 |
2 |

No evidence text available

No evidence text available
USP3 deubiquitinates CDC25A.
1 |
USP3 deubiquitinates CDC25A. 1 / 1
1 |

"<span class="match term0">USP3</span> was identified as a deubiquitinase of <span class="match term1">Cdc25A</span>"
USP3 decreases the amount of CDC25A.
| 1
USP3 decreases the amount of CDC25A. 1 / 1
| 1

reach
"USP3 depletion has been reported to reduce the Cdc25A protein level, resulting in a significant delay in cell cycle progression[33]."
USP3 affects AR
| 4
USP3 deubiquitinates AR.
| 3
USP3 deubiquitinates AR. 3 / 3
| 3

reach
"USP3 is also recruited by a novel lncRNA, AC092894.1, to promote AR (androgen receptor) deubiquitination and, subsequently, chemosensitivity to oxaliplatin[87]."

reach
"USP3 promotes transcription of RASGRP3 by deubiquitinating and stabilizing the transcription factor AR, and up-regulation of RASGRP3 increases CRC sensitivity to oxaliplatin [69]."

reach
"AC092894.1 serves as a scaffold molecule, enabling the deubiquitination of the androgen receptor (AR) by USP3, fostering the transcription of RASGRP3, and subsequently activating the MAPK signaling pathway, which augments oxaliplatin-induced apoptosis [73]."
USP3 activates AR.
| 1
USP3 activates AR. 1 / 1
| 1

reach
"Experiments found that the knockdown of USP3 promoted the protein degradation of AR (Fig. 6J)."
SND1-IT1 affects USP3
| 4
SND1-IT1 increases the amount of USP3. 4 / 4
| 4

reach
"It was found that, the expression of USP3 was evidently increased by SND1-IT1 overexpression, and was then partially reversed by miR-1245b-5p overexpression (Fig. 4J)."

reach
"The results of rescue experiment showed that USP3 expression increased by SND1-IT1 overexpression was partially reversed by overexpressed miR-1245b-5p."

reach
"Literature indicated that lncRNA might regulate downstream mRNA by recruiting RBP [23], thus we speculated that SND1-IT1 might promote USP3 expression via recruiting a RBP."

reach
"It was verified that SND1-IT1 can promote USP3 mRNA expression through competitively adsorbing miR-1245b-5p."
SMARCA5 affects K63
| 4
USP3 binds SMARCA5 and K63. 4 / 4
| 4

reach
"USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5."

reach
"These data demonstrate that USP3 regulates cellular response to docetaxel in prostate cancer cells in a SMARCA5 dependent manner.Collectively, we reveal that USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance (Fig. 6K)."

reach
"USP3 directly binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."

reach
"Mechanistically, USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5, which enhancing its stability."
PYCARD affects USP3
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
K63 affects SMARCA5, and USP3
| 4
USP3 binds SMARCA5 and K63. 4 / 4
| 4

reach
"USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5."

reach
"These data demonstrate that USP3 regulates cellular response to docetaxel in prostate cancer cells in a SMARCA5 dependent manner.Collectively, we reveal that USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance (Fig. 6K)."

reach
"USP3 directly binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5 to maintain its stability, which promotes DNA damage repair and chemotherapy resistance."

reach
"Mechanistically, USP3 binds SMARCA5 and removed K63-linked polyubiquitination of SMARCA5, which enhancing its stability."
4 |
Air Pollutants increases the amount of USP3.
2 |
Air Pollutants increases the amount of USP3. 2 / 2
2 |

No evidence text available

No evidence text available
Air Pollutants decreases the amount of USP3.
2 |
Air Pollutants decreases the amount of USP3. 2 / 2
2 |

No evidence text available

No evidence text available
Polyubiquitin affects USP3
| 3
Polyubiquitin binds USP3. 1 / 1
| 1

sparser
"Mutation analysis reveals that binding of USP3 to polyubiquitin chains on RIG-I is a prerequisite step for its cleavage of polyubiquitin chains."
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
USP3 binds polyubiquitin and IFIH1. 1 / 1
| 1

sparser
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [ xref ]."
Polyubiquitin chains affects USP3
| 3
USP3 binds polyubiquitin chains. 2 / 2
| 2

reach
"We further show that there is no interaction between USP3 and RIG-I-like receptors (RLRs) in unstimulated or uninfected cells, but upon viral infection or ligand stimulation, USP3 binds to the caspase activation recruitment domain of RLRs and then cleaves polyubiquitin chains through cooperation of its zinc-finger Ub binding domain and USP catalytic domains."

reach
"Mutation analysis reveals that binding of USP3 to polyubiquitin chains on RIG-I is a prerequisite step for its cleavage of polyubiquitin chains."
USP3 binds polyubiquitin chains and CARD domain. 1 / 1
| 1

reach
"[164] Upon viral infection or ligand stimulation, USP3 binds to the CARD domain of RIG-I and then removes its polyubiquitin chains through both the zinc-finger Ub binding domain and USP catalytic domains."
3 |
Cyclosporin A increases the amount of USP3. 3 / 3
3 |

No evidence text available

No evidence text available

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

No evidence text available

No evidence text available

No evidence text available
USP3 affects polyubiquitin
| 3
Polyubiquitin binds USP3. 1 / 1
| 1

sparser
"Mutation analysis reveals that binding of USP3 to polyubiquitin chains on RIG-I is a prerequisite step for its cleavage of polyubiquitin chains."
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
USP3 binds polyubiquitin and IFIH1. 1 / 1
| 1

sparser
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [ xref ]."
USP3 affects polyubiquitin chains
| 3
USP3 binds polyubiquitin chains. 2 / 2
| 2

reach
"We further show that there is no interaction between USP3 and RIG-I-like receptors (RLRs) in unstimulated or uninfected cells, but upon viral infection or ligand stimulation, USP3 binds to the caspase activation recruitment domain of RLRs and then cleaves polyubiquitin chains through cooperation of its zinc-finger Ub binding domain and USP catalytic domains."

reach
"Mutation analysis reveals that binding of USP3 to polyubiquitin chains on RIG-I is a prerequisite step for its cleavage of polyubiquitin chains."
USP3 binds polyubiquitin chains and CARD domain. 1 / 1
| 1

reach
"[164] Upon viral infection or ligand stimulation, USP3 binds to the CARD domain of RIG-I and then removes its polyubiquitin chains through both the zinc-finger Ub binding domain and USP catalytic domains."
USP3 affects gammaH2AX
| 3
USP3 deubiquitinates gammaH2AX.
| 2
Modified USP3 leads to the deubiquitination of gammaH2AX. 2 / 2
| 2

reach
"In addition, while USP3 depletion resulted in delayed disappearance of ubiquitylaed H2A and FK2 staining (poly-ubiquitylation marker) after IR, over-expression of USP3 suppressed ubiquitylation of gam[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Here, we showed that ectopic expression of USP3 led to the deubiquitination of both H2A and gammaH2AX in response to UV induced DNA damage."
USP3 activates gammaH2AX.
| 1
USP3 activates gammaH2AX. 1 / 1
| 1

reach
"In addition, while USP3 depletion resulted in delayed disappearance of ubiquitylaed H2A and FK2 staining (poly-ubiquitylation marker) after IR, over-expression of USP3 suppressed ubiquitylation of gam[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 3

reach
"USP3 upregulation attenuated IL-1β-mediated apoptosis of chondrocytes and inactivation of NF-κB pathway (107)."

reach
"Our results show that overexpression of USP3 could inhibits IL-1β-induced apoptosis, indicating that USP3 may be a negative regulator of OA development."

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."
USP3 affects Vif
| 2 1
USP3 inhibits Vif.
| 1
USP3 inhibits Vif. 1 / 1
| 1

reach
"Compared with full-length USP3, the UCH enzyme activity domain of USP3 strongly inhibited Vif-mediated A3G degradation [Figure 2E lane 5]."
USP3 deubiquitinates Vif.
| 1
USP3 deubiquitinates Vif. 1 / 1
| 1

reach
"Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner."
USP3 binds Vif.
| 1
USP3 binds Vif. 1 / 1
| 1

sparser
"Interestingly, we observed that USP3 also interacted with Vif."
USP3 affects UIMC1
1 | 2
USP3 inhibits UIMC1.
| 2
USP3 inhibits UIMC1. 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
"53BP1 and RAP80 foci are also negatively regulated by USP3 catalytic activity [18,110,132,135,136]."
USP3 deubiquitinates UIMC1.
1 |
USP3 deubiquitinates UIMC1. 1 / 1
1 |

"K63-linked ubiquitin accumulates on <span class="match term1">Rap80</span> at the DSB foci with the concerted effect of RNF8, RNF168, and Ubc13, which are clipped off with the assistance of <span class="match term0">USP3</span> and BRCC36 to maintain the G2/M checkpoint."
USP3 affects TLR
| 3
USP3 inhibits TLR.
| 2
USP3 inhibits TLR. 2 / 2
| 2

reach
"USP3 participates in the establishment of innate immune “tolerance” memory through a non-transcriptional feedback mechanism and negatively regulates TLR/IL1β-induced inflammatory signaling activation by specifically removing the K63-linked polyubiquitin chain on MyD88."

reach
"The deficiency of USP3 enhances TLR-mediated proinflammatory responses."
USP3 decreases the amount of TLR.
| 1
USP3 decreases the amount of TLR. 1 / 1
| 1

reach
"USP3 deficiency dramatically enhances the release of TLR‐induced inflammatory cytokines, suggesting that these K63‐linked polyubiquitin chains might play a pivotal role in activating NF‐κB signaling."
USP3 affects TBK1
| 1 1 1
USP3 inhibits TBK1. 3 / 3
| 1 1 1

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

reach
"To determine the specificity of the USP38-mediated TBK1 degradation, we used other USP family members USP3 and USP13 as a control, and we found that USP38, but not USP3 or USP13, induced TBK1 degradat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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

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 ]."
USP3 binds STING1.
1 |
1 |

No evidence text available
USP3 affects SIRT3
| 1 2
USP3 deubiquitinates SIRT3.
| 1
USP3 deubiquitinates SIRT3. 1 / 1
| 1

reach
"On the other hand, deubiquitination may also exert a protective effect on OA in an acetylation-dependent manner, as overexpressed USP3 deubiquitinates SIRT3, which promotes SIRT3-dependent deacetylati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 deacetylates SIRT3.
| 1
USP3 leads to the deacetylation of SIRT3. 1 / 1
| 1

reach
"On the other hand, deubiquitination may also exert a protective effect on OA in an acetylation-dependent manner, as overexpressed USP3 deubiquitinates SIRT3, which promotes SIRT3-dependent deacetylati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 activates SIRT3.
| 1
USP3 activates SIRT3. 1 / 1
| 1

eidos
"USP3 upregulated SIRT3 to deacetylate FOXO3 and attenuated IL-1beta-induced chondrocyte senescence ."
USP3 affects PLK1
| 3
| 3

sparser
"Co-immunoprecipitation and Western blotting were used to validate the USP3-PLK1 interaction and to assess PLK1 ubiquitination."

sparser
"Mechanistically, USP3 bound to PLK1, reduced K48-linked ubiquitination of PLK1, and stabilized PLK1 protein levels."

sparser
"Targeting the USP3-PLK1 axis may represent a potential therapeutic strategy for glioma."
USP3 affects Osteosarcoma
| 3
USP3 activates Osteosarcoma.
| 2
| 2

reach
"Functional studies further demonstrated that USP3 promotes osteosarcoma cell proliferation and tumor growth both in vitro and in vivo."

reach
"USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway."
USP3 inhibits Osteosarcoma.
| 1
| 1

reach
"Through in vitro cell proliferation (Fig. 2C), colony formation (Fig. 2D), migration (Fig. 2E), wound healing (Supplemental Fig. 1C) and invasion (Fig. 2F) assay, we found that downregulation of USP3 inhibited the proliferation, migration and invasion of osteosarcoma cells."
USP3 affects Infections
| 3
| 3

reach
"To examine why the ZNF domain of USP3 lacking deubiquitination activity also stabilizes A3G and inhibits HIV-1 infection, we performed deubiquitination experiments in vivo and in vitro."

reach
"Further experiments found that USP3 indeed inhibited HIV-1 infection by stabilizing A3G in a dose-dependent manner, although it had no effect on HIV production in the absence of A3G."

reach
"The results showed that USP3 WT, ZNF domain, and UCH domain all stabilized the expression of A3G [Figure 2F] and inhibited HIV-1 infection [Figure 2G]."
USP3 affects ISLR
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP3 affects IL1B
| 3
USP3 inhibits IL1B. 3 / 3
| 3

reach
"Consistent with previous reports, this study showed that both IL-1β induction and knockdown of USP3 could increase MMP-1/MMP-13 expression, while overexpression of USP3 could block IL-1β effects on MM[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In contrast, USP3 overexpression could reverse the inhibitory effect of IL-1β on IKBα expression."

reach
"USP3 over expression could partly reverse these IL-1β effects ( Fig. 2 E)."
USP3 affects His2A
| 3
USP3 inhibits His2A.
| 2
USP3 inhibits His2A. 2 / 2
| 2

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."

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 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 affects Glioblastoma
| 2 1
| 2 1

eidos
"The dual-luciferase reporter assay also revealed that lncRNA HOXA-AS3 acts as a mir-455-5p sponge by up-regulating USP3 expression to promote GBM progression ."

reach
"However, USP3 has been demonstrated to promote EMT and tumourigenesis in glioblastoma in vitro and in vivo ( Fan et al. 2019 )."

eidos
"Previous studies have shown that USP3 raised GBM progression by regulating EMT ."
USP3 affects DNA Damage
| 3
USP3 inhibits DNA Damage.
| 2
| 2

reach
"Moreover, the loss of USP3 leads to a preference for hematopoietic stem cells (HSCs) to endure more DNA damage and accumulate spontaneous DNA damage."

reach
"USP3 regulates mitotic progression, and USP3 deficiency induces DNA damage leading to replication defects and S-phase delays as well as activation of the corresponding checkpoints [17]."
USP3 activates DNA Damage.
| 1
| 1

reach
"It promotes cell proliferation, invasion, migration, DNA damage repair, and glycolysis, potentially via the Wnt/β-catenin signaling pathway.14 Similarly, USP3 promotes cholangiocarcinoma proliferation and invasion through the Wnt/MYC pathway, enhancing tumor cell glycolysis, energy production, and upregulating metabolic target genes such as GLUT1, HK2, PDM2, and LDHA.87 Egfr/Stat3."
USP3 affects APOBEC3G
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP3 affects ACOT7
| 3
USP3 increases the amount of ACOT7. 3 / 3
| 3

reach
"Tao et al. found that ubiquitin-specific protease 3 (USP3) upregulated the expression of the ACOT7 protein through a deubiquitination mechanism, whereas downregulation of USP3 markedly elevated the expression of ACSL4 and promoted ferroptosis in NSCLC cells [71]."

reach
"Mechanistically, USP3 upregulated ACOT7 protein expression through deubiquitination."

reach
"To conclude, USP3 upregulated ACOT7 protein expression through deubiquitination, thereby repressing ferroptosis in NSCLC cells and enhancing DDP resistance."
PLK1 affects USP3
| 3
| 3

sparser
"Co-immunoprecipitation and Western blotting were used to validate the USP3-PLK1 interaction and to assess PLK1 ubiquitination."

sparser
"Mechanistically, USP3 bound to PLK1, reduced K48-linked ubiquitination of PLK1, and stabilized PLK1 protein levels."

sparser
"Targeting the USP3-PLK1 axis may represent a potential therapeutic strategy for glioma."
PKLR affects USP3
1 | 2
1 | 2

sparser
"These findings imply that USP3 is an essential positive regulator in GBC progression, and USP3-PKLR plays a vital role in the progression and metabolism of GBC."

No evidence text available

sparser
"These findings imply that USP3 is an essential positive regulator in GBC progression, and USP3-PKLR plays a vital role in the progression and metabolism of GBC."
PDS5B affects USP3
| 2 1
PDS5B decreases the amount of USP3.
| 1
PDS5B decreases the amount of USP3. 1 / 1
| 1

reach
"Western blot analysis showed that down‐regulation of lncRNA HOXA‐AS3 inhibits USP3 expression and EMT in vivo (Figure 6E).4 DISCUSSION."
PDS5B binds USP3.
| 1
USP3 binds PDS5B and hoxA. 1 / 1
| 1

sparser
"In conclusion, we found an associated lncRNA network that regulates the tumour cell development network, consisting of lncRNA HOXAAS3, miR‐455‐5p and USP3."
PDS5B activates USP3.
| 1
PDS5B activates USP3. 1 / 1
| 1

reach
"These results indicate that lncRNA HOXA‐AS3 can promote glioma progression by regulating the miR‐455‐5p/ USP3 axis.Epithelial‐mesenchymal transition is a process in which epithelial cells are transformed into mesenchymal cells and acquire motile and invasive characteristics."
ISLR affects USP3
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No evidence text available

No evidence text available
HNF1A affects USP3
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HNF1A decreases the amount of USP3. 3 / 3
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No evidence text available

No evidence text available

No evidence text available
APOBEC3G affects USP3
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No evidence text available

No evidence text available

No evidence text available
2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP3.
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No evidence text available

No evidence text available
2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP3.
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No evidence text available
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Valproic acid increases the amount of USP3.
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Valproic acid increases the amount of USP3. 1 / 1
1 |

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

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

No evidence text available
Titanium dioxide demethylates USP3.
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1 |

No evidence text available
Rep affects USP3
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No evidence text available
| DOI

No evidence text available
| DOI
Polyubiquitin affects IFIH1
| 2
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
USP3 binds polyubiquitin and IFIH1. 1 / 1
| 1

sparser
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [ xref ]."

sparser
"The inhibition of USP3 by PEITC in living cells was confirmed by observing the molecular shift upon probe labeling by immunoblotting (Figure xref )."

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

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

No evidence text available
MiR-224-5p affects USP3
| 2
MiR-224-5p decreases the amount of USP3. 2 / 2
| 2

reach
"MiR-224-5p overexpression decreased USP3 expression."

reach
"RT-qPCR also showed that miR-224-5p overexpression decreased USP3 expression, while overexpression of USP3 increased USP3 expression ( Fig. 5 C, D)."
LncRNA HOXA-AS3 affects USP3
| 2
LncRNA HOXA-AS3 activates USP3. 2 / 2
| 2

eidos
"We also found that lncRNA HOXA-AS3 could act as a miRNA sponge to reduce miR-455-5p concentration , up-regulate USP3 expression and drive the epithelial-mesenchymal transition ( EMT ) process of GBM cells ."

eidos
"Western blot analysis showed that down-regulation of lncRNA HOXA-AS3 inhibits USP3 expression and EMT in vivo ( Figure 6E ) ."
2 |
Hsa-miR-26b-5p decreases the amount of USP3. 2 / 2
2 |

No evidence text available

No evidence text available

No evidence text available
Bis(2-ethylhexyl) phthalate increases the amount of USP3.
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Bis(2-ethylhexyl) phthalate increases the amount of USP3. 1 / 1
1 |

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

No evidence text available
Aflatoxin B1 demethylates USP3.
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Aflatoxin B1 demethylates USP3. 1 / 1
1 |

No evidence text available
Ubiquitin affects USP3
| 2

sparser
"Compound 59 Binds the C-Terminal Ubiquitin Binding Site of USP3."

sparser
"Experiments confirmed that mutation of UBP ZnF significantly reduced the interaction of USP3 with ubiquitinated histone uH2A both in vivo and in vitro, suggesting that this is the major domain mediating the interaction between USP3 and ubiquitin [ xref ]."
USP3 affects rep
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2 |

No evidence text available
| DOI

No evidence text available
| DOI

reach
"According to literature review, USP3 can mediate protein deubiquitination by acting as a deubiquitinase to promote protein expression and regulate cancer progression [24]."

reach
"As USP3 can mediate protein deubiquitination, we used BioGrid to predict the proteins which can interact with USP3."

reach
"Mechanistically, USP3 activated PI3K/AKT signaling pathway through binding to EPHA2 and then reducing its protein degradation."

reach
"Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation."
| 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 cisplatin
| 2
| 2

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"The results showed that knockdown of USP3 markedly reduced the viability of cisplatin-treated cells, while overexpression of USP3 significantly induced DDP resistance (Supplemental Fig. 1D)."

reach
"USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis."
| 1

reach
"Silencing of USP3 reduces the self-renewal capacity of NB cells and promotes differentiation induced by retinoic acid."
| 1

reach
"Through the regulation of H2AK119ub, USP3 promotes leukemia cell differentiation, suggesting its potential therapeutic role in leukemia."
USP3 affects angiogenesis
| 2
| 2

reach
"Moreover, the tube formation assay illustrated that USP3 could inhibit angiogenesis (Fig. S3E)."

reach
"Subsequently, we found USP3 overexpression significantly suppressed cell malignant phenotypes and angiogenesis in RCC."
USP3 affects activity
| 2
USP3 inhibits activity. 2 / 2
| 2

sparser
"Ectopic expression of USP3 inhibited IFN-β promoter activity in cells treated with low molecular weight (LMW) poly(I:C), and in cells infected with VSV."

sparser
"Ectopic expression of USP3 inhibited IFN-β promoter activity in cells treated with high molecular weight (HMW) poly(I:C), whereas gene silencing of USP3 enhanced IFN-β protein expression under similar treatment."
| 2

reach
"Overall, our data suggest that USP3 protein expression levels in HIV-1-infected individuals can be used to indicate HIV viral load and may serve as a new biomarker for evaluating the prognosis of HIV-1-infected patients.In summary, we found that USP3 restricts HIV-1 viral infections by increasing the expression of antiviral factor A3G."

reach
"Conclusions:. USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G."
USP3 affects USP17L2
| 2
USP3 deubiquitinates USP17L2. 2 / 2
| 2

reach
"Extensive immunoreactivity of CD163, scavenger receptor class B, member 1 (SRBI) and deubiquitinating enzyme 3 (Dub3) was a prominent feature of DSCLs compared to both NAWM from lesional cases and control WM from non-lesional cases."

reach
"Similarly, ubiquitin-processing proteases, such as ubiquitin-specific-processing protease 11 (USP11) and deubiquitinating enzyme 3 (DUB3), catalyze the removal of ubiquitin from NRF2, thereby stabilizing NRF2 protein [34,35]."
USP3 affects STS
| 2
USP3 deubiquitinates STS.
| 1
USP3 deubiquitinates STS. 1 / 1
| 1

reach
"USP3 deubiquitinates and stabilizes the adapter protein ASC to regulate inflammasome activation."
USP3 activates STS.
| 1
USP3 activates STS. 1 / 1
| 1

reach
"73 Additionally, Zhuang et al. proposed that USP3 enhances ASC stability by eliminating the K‐48 linked ubiquitin chain."
USP3 affects RIG-I-like receptors
| 2
USP3 ubiquitinates RIG-I-like receptors.
| 1
USP3 leads to the ubiquitination of RIG-I-like receptors. 1 / 1
| 1

reach
"Ubiquitin-specific protease 3 (USP3) has been reported to inhibit type I interferon signaling via deubiquitination of RIG-I-like receptors and antiviral immunity (106)."
USP3 deubiquitinates RIG-I-like receptors.
| 1
USP3 leads to the deubiquitination of RIG-I-like receptors. 1 / 1
| 1

reach
"Ubiquitin-specific protease 3 (USP3) has been reported to inhibit type I interferon signaling via deubiquitination of RIG-I-like receptors and antiviral immunity (106)."
USP3 affects RBM4
| 2
USP3 activates RBM4. 2 / 2
| 2

reach
"USP3 was manifested to promote lung cancer growth through upregulating RBM4 via acting as a DUB [30], and USP5 contributed to cell proliferation via stabilizing cyclin D1 protein level in lung cancer [31]."

reach
"USP3 has recently been shown to promote cell proliferation by targeting RBM4 (RNA binding motif 4) [43] or KLF5 (Krüppel-like factor 5) [44] in non-small cell lung and breast cancer cells, respectivel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 affects Protease
| 2
USP3 activates Protease. 2 / 2
| 2

reach
"USP3 produces a protease that breaks down and modulates many intracellular proteins and eliminates damaged and misfolded proteins and regulates cellular processes as apoptosis."

reach
"52 Overall, USP3 primarily functions as a tumor promoter in GC, driving GC cell proliferation, invasion, migration, and the EMT process.Ubiquitin‐specific protease 3 has also been implicated in esophageal squamous cell carcinoma (ESCC)."
USP3 affects Phosphatase
| 2
USP3 increases the amount of Phosphatase.
| 1
USP3 increases the amount of Phosphatase. 1 / 1
| 1

reach
"Knockdown of USP3 decreases the level of CDC25A phosphatase, resulting in cell cycle delay [32]."
USP3 deubiquitinates Phosphatase.
| 1
USP3 deubiquitinates Phosphatase on A25. 1 / 1
| 1

reach
"USP3 deubiquitinates and stabilizes the cell division cycle 25A (Cdc25A), a bispecific phosphatase that regulates the cell cycle, and degradation of Cdc25A in the presence of DNA damage causes cells to arrest in G1 phase [24]."
USP3 affects PI3K
| 2
USP3 activates PI3K. 2 / 2
| 2

reach
"Mechanistically, USP3 activated PI3K/AKT signaling pathway through binding to EPHA2 and then reducing its protein degradation."

reach
"Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation."
USP3 affects PDZK1
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No evidence text available

No evidence text available
USP3 affects OXT
| 2

sparser
"Our data showed strong positive correlations between MALAT1 expression and the expression of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5 (Fig. xref ), highlighting a plausible reciprocal relationship between MALAT1 and the identified lncRNAs in TNBC."

sparser
"We suggest a possible reciprocal relationship between MALAT1 and each of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5."
USP3 affects NT5E
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2 |

No evidence text available

No evidence text available
USP3 affects NANOG
1 | 1
USP3 deubiquitinates NANOG. 2 / 2
1 | 1

reach
"For example, USP3 has recently been shown to deubiquitinate and stabilize OCT4 in hESCs (48), whereas USP21 has been previously identified to deubiquitinate NANOG in mESCs by screening a large number of DUBs including USP7 (19–21)."
USP3 affects MUC20
| 2

sparser
"Our data showed strong positive correlations between MALAT1 expression and the expression of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5 (Fig. xref ), highlighting a plausible reciprocal relationship between MALAT1 and the identified lncRNAs in TNBC."

sparser
"We suggest a possible reciprocal relationship between MALAT1 and each of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5."
USP3 affects KIFC1
| 2
USP3 increases the amount of KIFC1. 2 / 2
| 2

reach
"As initial validation, transfection with these siRNA pools was repeated once more, confirming that depletion of USP3, OTUD6B, JOSD2, or UCHL1 decreased KIFC1 protein levels (Fig. 1E)."

reach
"For example, all four USP10 or USP3 siRNAs effectively depleted their target DUB, but only one siRNA reduced KIFC1 levels (Appendix Fig. S2B,C)."
USP3 affects K63-polyubiquitin chains
| 2
USP3 activates K63-polyubiquitin chains. 2 / 2
| 2

reach
"For example, ubiquitin-specific peptidase 3 (USP3), USP21, and cylindromatosis lysine 63 deubiquitinase (CYLD) modulate RIG-I signaling by removing K63-polyubiquitin chains (Cui et al., 2014; Fan et al., 2014)."

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 IKKβ protein
| 2
USP3 increases the amount of IKKβ protein.
| 1
USP3 increases the amount of IKKβ protein. 1 / 1
| 1

reach
"Silencing USP3 significantly reduces IKKβ protein levels."
USP3 deubiquitinates IKKβ protein.
| 1
USP3 leads to the deubiquitination of IKKβ protein. 1 / 1
| 1

reach
"In turn, USP3 mediates IKKβ protein deubiquitylation and enhances protein stability, promoting NPC development by activating the nuclear factor‐κB (NF‐κB) pathway."
USP3 affects IFN-I
| 2
USP3 inhibits IFN-I. 2 / 2
| 2

reach
"USP3 diminishes IFN-I response through activation removal of Lys63-linked polyUb chains from RIG-1."

reach
"USP3 negatively regulates the activation of type 1 interferon (IFN-I) signaling by specifically targeting Retinoic acid-inducible gene I lysine 63(RIG-I K63)-linked polyubiquitin chains and removing them, resulting in IFN-I inhibition."
USP3 affects H2BC21
1 | 1
USP3 deubiquitinates H2BC21. 2 / 2
1 | 1

"<span class="match term0">USP3</span> dynamically associates with chromatin and deubiquitinates H2A/<span class="match term1">H2B</span> in vivo"

reach
"USP3 dynamically associates with chromatin and deubiquitylates uH2A/uH2B in vivo ."
USP3 affects GST
| 2
| 2

sparser
"In addition, GST pull-down assays were performed to validate the in vitro results showing that GST-USP3 effectively decreased COL9A3 and COL6A5 recombinant proteins in AGS cells."

sparser
"USP3-GST fusion protein were expressed in BL21 competent cells and purified with Glutathione sepharose 4B. Ubiquitinated p53 protein was incubated with recombinant USP3 in the deubiquitination buffer [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 affects GPC1
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No evidence text available

No evidence text available
USP3 affects Fan
| 2
USP3 activates Fan. 2 / 2
| 2

reach
"However, USP3 has been demonstrated to promote EMT and tumourigenesis in glioblastoma in vitro and in vivo ( Fan et al. 2019 )."

reach
"Previous studies found that USP3 expression promotes cancer progress ( Fan et al., 2019; Wu et al., 2019 )."
USP3 affects FLVCR1
| 2
USP3 activates FLVCR1. 2 / 2
| 2

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"Nevertheless, our results reveal that USP3 regulates the stability, ubiquitination and thus the function of SMARCA5, providing a mechanistic link between the deubiquitinase USP3 and the SMARCA5-mediated DDR.In summary, we demonstrate that deletion of USP3 inhibits PCa cell growth in vitro and in vivo."

reach
"To elucidate the molecular mechanism of USP3-mediated PCa progression, we performed immunoaffinity purification and mass spectrometry (MS) analysis of USP3 interactors (Fig. 3A)."

reach
"USP3 [57], USP16 [58], USP29 [59], USP44 [59], USP49 [60], USP51 [61], A20 [62], BRCC36 [63], and OTUB1 [64] have been suggested to inhibit DSB-induced histone H2A ubiquitination."

reach
"Knockdown of USP3 alone activates the DSB response, as determined by a number of factors including a delay in S-phase progression, an increased number of DNA breaks and structural abnormalities, ATM/ATR activation, and γH2AX staining [109,132,134]."
USP3 affects DDX54
| 1 1
| 1 1

sparser
"It was shown that the binding of DDX54 with USP3 3’UTR was enhanced after SND1-IT1 overexpression (Fig.  xref H)."

reach
"It was shown that the binding of DDX54 with USP3 3’UTR was enhanced after SND1-IT1 overexpression (Fig. 5H)."
USP3 affects ALYREF
| 2
USP3 inhibits ALYREF.
| 1
USP3 inhibits ALYREF. 1 / 1
| 1

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."
USP3 binds ALYREF.
| 1
ALYREF binds USP3 and MYCN. 1 / 1
| 1

reach
"The ALYREF-USP3-MYCN complex is a potential therapeutic target for NB by exploiting obligatory ALYREF dependence in MYCN-amplified cells [37]."
USP3 affects ACSL4
| 2
USP3 increases the amount of ACSL4. 2 / 2
| 2

reach
"Moreover, USP3 silencing suppressed GSH and GPX4 levels, upregulated iron ion contents, ROS, MDA, and ACSL4 levels, and facilitated ferroptosis."

reach
"Tao et al. found that ubiquitin-specific protease 3 (USP3) upregulated the expression of the ACOT7 protein through a deubiquitination mechanism, whereas downregulation of USP3 markedly elevated the expression of ACSL4 and promoted ferroptosis in NSCLC cells [71]."
TGFB1 affects USP3
| 2
TGFB1 increases the amount of USP3. 2 / 2
| 2

sparser
"Blocking TGF-β1 with a neutralizing antibody significantly suppressed endogenous USP3 expression and TGF-β1-induced USP3 expression in BGC-823 cells (Additional file xref : Figure S2C)."

sparser
"Moreover, TGF-β1 induced USP3 expression, and USP3 knockdown inhibited TGF-β1-induced EMT."
SMO affects USP3
| 2
SMO increases the amount of USP3.
| 1
SMO increases the amount of USP3. 1 / 1
| 1

reach
"SMO enhances the radiation resistance of GBM cells by promoting the transcription of USP3 and activating Claspin-dependent ATR-Chk1 signaling [48]."
SMO decreases the amount of USP3.
| 1
SMO decreases the amount of USP3. 1 / 1
| 1

reach
"Moreover, we found that Smo reduced Claspin polyubiquitination and proteasomal degradation by promoting USP3 transcription."
SMAD4 affects USP3
| 2
| 2

reach
"We utilized luciferase reporter constructs of PGL3-USP3 3 ' UTR and PGL3-SMAD4 3 ' UTR to evaluate whether the interaction between USP3 and SMAD4 was 3 ' UTR dependent."

reach
"This reversal was partially due to the ceRNA interaction between USP3 and SMAD4."
RT-qPCR affects USP3
| 2
RT-qPCR decreases the amount of USP3. 2 / 2
| 2

reach
"RT-qPCR showed that downregulation of hsa_circ_0017639 decreased USP3 expression."

reach
"RT-qPCR also showed that miR-224-5p overexpression decreased USP3 expression, while overexpression of USP3 increased USP3 expression ( Fig. 5 C, D)."
RIGI affects IFIH1
| 2
USP3 binds RIGI and IFIH1. 2 / 2
| 2

sparser
"The interaction of USP3 with RIG-I and MDA5 is strictly based upon ligand stimulation."

sparser
"Also co-IP demonstrated the interaction between USP3 and stimulated RIG-I or MDA5, but not the unstimulated ones, supporting that ligand stimulation is required for USP3 to interact with RIG-I or MDA5 [ xref ]."
PDZK1 affects USP3
2 |
2 |

No evidence text available

No evidence text available
OXT affects USP3
| 2

sparser
"Our data showed strong positive correlations between MALAT1 expression and the expression of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5 (Fig. xref ), highlighting a plausible reciprocal relationship between MALAT1 and the identified lncRNAs in TNBC."

sparser
"We suggest a possible reciprocal relationship between MALAT1 and each of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5."
USP3 is modified
| 1 1
USP3 is phosphorylated.
| 1
USP3 is phosphorylated. 1 / 1
| 1

sparser
"Importantly, we observed that the augmented phosphorylation of downstream protein kinases in  USP3 −/− or USP3 KD cells were markedly enhanced after LPS pretreatment (Figs  xref and xref ) compared with the non‐pretreatment results shown in Figs  xref and xref (Appendix Fig  xref )."
USP3 is produced.
| 1
USP3 is produced. 1 / 1
| 1

reach
"77 Jin et al. 52 found that the mRNA level of USP3 is significantly upregulated by lncRNA SND1‐IT1 overexpression and decreased by miR‐1245b‐5p overexpression."
NT5E affects USP3
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2 |

No evidence text available

No evidence text available
MicroRNA-146-5p affects USP3
| 2
MicroRNA-146-5p activates USP3. 2 / 2
| 2

reach
"MicroRNA-146-5p Promotes Pulmonary Artery Endothelial Cell Proliferation under Hypoxic Conditions through Regulating USP3."

reach
"MicroRNA-146-5p was able to enhance the proliferation ability of HPAEC cells under hypoxic conditions through targeting USP3, suggesting the microRNA-146-5p/USP3 axis may act as a target for PAH treatment."
MYCN affects USP3
| 1 1
| 1

sparser
"USP3 interacts directly with its protein targets, which prompted us to examine whether MYCN also bound USP3 directly."
ALYREF binds USP3 and MYCN. 1 / 1
| 1

reach
"The ALYREF-USP3-MYCN complex is a potential therapeutic target for NB by exploiting obligatory ALYREF dependence in MYCN-amplified cells [37]."
MUC20 affects USP3
| 2

sparser
"Our data showed strong positive correlations between MALAT1 expression and the expression of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5 (Fig. xref ), highlighting a plausible reciprocal relationship between MALAT1 and the identified lncRNAs in TNBC."

sparser
"We suggest a possible reciprocal relationship between MALAT1 and each of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5."
LEF1 affects USP3
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LEF1 decreases the amount of USP3. 2 / 2
2 |

No evidence text available

No evidence text available
IL1B affects USP3
| 2
IL1B decreases the amount of USP3. 2 / 2
| 2

reach
"Both Western blot and real-time PCR results showed that IL-1β could inhibit USP3 expression levels and the inhibition effects were dose-interdependent with IL-1β concentration ( Fig. 1 F and G)."

reach
"Further, through Western blot, we found that IL-1β induced chondrocytes significantly downregulated USP3 and IkBα expression levels, while caspase3, MMP1, MMP13 were upregulated."
IFIH1 affects polyubiquitin
| 2
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
USP3 binds polyubiquitin and IFIH1. 1 / 1
| 1

sparser
"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [ xref ]."
IFIH1 affects RIGI, and USP3
| 2
USP3 binds RIGI and IFIH1. 2 / 2
| 2

sparser
"The interaction of USP3 with RIG-I and MDA5 is strictly based upon ligand stimulation."

sparser
"Also co-IP demonstrated the interaction between USP3 and stimulated RIG-I or MDA5, but not the unstimulated ones, supporting that ligand stimulation is required for USP3 to interact with RIG-I or MDA5 [ xref ]."
Histone affects USP3
| 2
| 2

sparser
"USP3 does in fact interact with ubiquitinated H2A-type histones, and mouse embryonic fibroblasts isolated from USP3-null mice express increased levels of ubiquitinated H2A [ xref ]."

sparser
"Experiments confirmed that mutation of UBP ZnF significantly reduced the interaction of USP3 with ubiquitinated histone uH2A both in vivo and in vitro, suggesting that this is the major domain mediating the interaction between USP3 and ubiquitin [ xref ]."
HAUS3 affects USP3
| 2
HAUS3 increases the amount of USP3.
| 1
HAUS3 increases the amount of USP3. 1 / 1
| 1

reach
"77 Jin et al. 52 found that the mRNA level of USP3 is significantly upregulated by lncRNA SND1‐IT1 overexpression and decreased by miR‐1245b‐5p overexpression."
HAUS3 activates USP3.
| 1
HAUS3 activates USP3. 1 / 1
| 1

reach
"They further discovered that USP3 mRNA stability is promoted by SND1‐IT1 through recruitment of RNA binding protein DDX54."
H2AC20 affects USP3
| 2
| 1

sparser
"Based on its zinc-finger Ub-binding domain (ZnF-UBP) and a catalytic domain of the Ub-specific protease (USP) class, the ZnF-UBP domain of USP3 mediates monoubiquitinated H2A (uH2A)-USP3 interaction, which affected DNA damage response [ xref ]."
| 1

sparser
"Both USP3 and USP16 are also associated with H2A deubiquitination following DNA damage processing [ xref , xref ]."
GST affects USP3
| 2
| 2

sparser
"In addition, GST pull-down assays were performed to validate the in vitro results showing that GST-USP3 effectively decreased COL9A3 and COL6A5 recombinant proteins in AGS cells."

sparser
"USP3-GST fusion protein were expressed in BL21 competent cells and purified with Glutathione sepharose 4B. Ubiquitinated p53 protein was incubated with recombinant USP3 in the deubiquitination buffer [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
GPC1 affects USP3
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No evidence text available

No evidence text available
FOXO4 affects USP3
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FOXO4 decreases the amount of USP3. 2 / 2
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No evidence text available

No evidence text available
FBXL22 affects USP3
| 1 1
FBXL22 decreases the amount of USP3.
| 1
FBXL22 decreases the amount of USP3. 1 / 1
| 1

reach
"Among SNPs at the locus with P < 1 × 10 , many have been reported as cis-eQTLs in whole blood and other tissues with febrile seizures risk alleles corresponding to decreased expression of HERC1, USP3, DAPK2 and PLEKHO2, and increased expression of FBXL22, APH1B and RBPMS2 (Supplementary Table 5)."
FBXL22 binds USP3.
| 1
| 1

sparser
"The PRL and SOX4 protein-coding genes are associated with CASC15 , PPP1R26 is associated with PPP1R26-AS1 , and USP3 and FBXL22 are associated with USP3-AS1 ."
ETS2 affects USP3
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ETS2 decreases the amount of USP3. 2 / 2
2 |

No evidence text available

No evidence text available
Dronabinol affects USP3
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Dronabinol increases the amount of USP3. 2 / 2
2 |

No evidence text available

No evidence text available

sparser
"Our data showed strong positive correlations between MALAT1 expression and the expression of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5 (Fig. xref ), highlighting a plausible reciprocal relationship between MALAT1 and the identified lncRNAs in TNBC."

sparser
"We suggest a possible reciprocal relationship between MALAT1 and each of AC005154.1, NEAT1, AL139022.1, AC007622.2, USP3-AS1, MUC20-OT1, LINC-PINT, and AC103810.5."
DDX54 affects USP3
| 1 1
| 1 1

sparser
"It was shown that the binding of DDX54 with USP3 3’UTR was enhanced after SND1-IT1 overexpression (Fig.  xref H)."

reach
"It was shown that the binding of DDX54 with USP3 3’UTR was enhanced after SND1-IT1 overexpression (Fig. 5H)."
CDC25A affects USP3
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2 |

No evidence text available

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

reach
"MYCN, a stable oncogenic transcription factor, is tightly regulated by the ubiquitin-proteasome system and partially relies on ALYREF for promoting enhanced cancer cell viability and proliferation [49], while ALYREF inhibits MYCN degradation by directly transcribing USP3 at levels necessary to facilitate tumor growth."
ALYREF binds USP3.
| 1
ALYREF binds USP3 and MYCN. 1 / 1
| 1

reach
"The ALYREF-USP3-MYCN complex is a potential therapeutic target for NB by exploiting obligatory ALYREF dependence in MYCN-amplified cells [37]."

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

No evidence text available
Transcriptional activator increases the amount of USP3. 1 / 1
| 1

reach
"ALYREF and MYCN form a transcriptional activator complex, which upregulates USP3 expression, promoting the growth and tumorigenicity of MYCN-amplified neuroblastoma cells [24]."
Rotenone affects USP3
1 |
Rotenone increases the amount of USP3. 1 / 1
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No evidence text available
Polyubiquitin affects K63
| 1
Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
| 1

sparser
"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
Polyubiquitin chains affects CARD domain
| 1
USP3 binds polyubiquitin chains and CARD domain. 1 / 1
| 1

reach
"[164] Upon viral infection or ligand stimulation, USP3 binds to the CARD domain of RIG-I and then removes its polyubiquitin chains through both the zinc-finger Ub binding domain and USP catalytic domains."
1 |

No evidence text available
| 1

sparser
"The two proteins form a nuclear coactivator complex which stimulates transcription of the ubiquitin specific peptidase 3, USP3."
1 |
Pentachlorophenol decreases the amount of USP3. 1 / 1
1 |

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

No evidence text available
Nuclear coactivator increases the amount of USP3. 1 / 1
| 1

reach
"In neuroblastoma patients, the m C reader ALYREF forms a nuclear coactivator complex with MYCN to stimulate USP3 transcription, which promotes the tumorigenesis of neuroblastoma (89)."
Nefazodone affects USP3
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Nefazodone increases the amount of USP3. 1 / 1
1 |

No evidence text available
MicroRNA-146-5p affects USP3
| 1
MicroRNA-146-5p binds USP3. 1 / 1
| 1

reach
"In addition, the interaction between microRNA-146-5p and USP3 was examined by luciferase reporting assay."
MiR-33a affects USP3
| 1
MiR-33a decreases the amount of USP3. 1 / 1
| 1

reach
"For supportive host factors, miR-1-3p, miR-17-3p, miR-193b, miR-203, miR-221, miR-26a, miR-30, miR-324-5p, miR-33a, and miR-548an respectively inhibit the expression of ATP6V1A, GALNT3, β-catenin, DR1, GALNT3, USP3, NEDD4, CUEDC2, ARCN1, and NS1ABP to inhibit IAV replication ultimately, but miR-34c promotes PLK4 expression to promote IAV replication."
MiR-30 affects USP3
| 1
MiR-30 decreases the amount of USP3. 1 / 1
| 1

reach
"For supportive host factors, miR-1-3p, miR-17-3p, miR-193b, miR-203, miR-221, miR-26a, miR-30, miR-324-5p, miR-33a, and miR-548an respectively inhibit the expression of ATP6V1A, GALNT3, β-catenin, DR1, GALNT3, USP3, NEDD4, CUEDC2, ARCN1, and NS1ABP to inhibit IAV replication ultimately, but miR-34c promotes PLK4 expression to promote IAV replication."
MiR-203 affects USP3
| 1
MiR-203 decreases the amount of USP3. 1 / 1
| 1

reach
"For supportive host factors, miR-1-3p, miR-17-3p, miR-193b, miR-203, miR-221, miR-26a, miR-30, miR-324-5p, miR-33a, and miR-548an respectively inhibit the expression of ATP6V1A, GALNT3, β-catenin, DR1, GALNT3, USP3, NEDD4, CUEDC2, ARCN1, and NS1ABP to inhibit IAV replication ultimately, but miR-34c promotes PLK4 expression to promote IAV replication."
MiR-193b affects USP3
| 1
MiR-193b decreases the amount of USP3. 1 / 1
| 1

reach
"For supportive host factors, miR-1-3p, miR-17-3p, miR-193b, miR-203, miR-221, miR-26a, miR-30, miR-324-5p, miR-33a, and miR-548an respectively inhibit the expression of ATP6V1A, GALNT3, β-catenin, DR1, GALNT3, USP3, NEDD4, CUEDC2, ARCN1, and NS1ABP to inhibit IAV replication ultimately, but miR-34c promotes PLK4 expression to promote IAV replication."
MiR-17-3p affects USP3
| 1
MiR-17-3p decreases the amount of USP3. 1 / 1
| 1

reach
"For supportive host factors, miR-1-3p, miR-17-3p, miR-193b, miR-203, miR-221, miR-26a, miR-30, miR-324-5p, miR-33a, and miR-548an respectively inhibit the expression of ATP6V1A, GALNT3, β-catenin, DR1, GALNT3, USP3, NEDD4, CUEDC2, ARCN1, and NS1ABP to inhibit IAV replication ultimately, but miR-34c promotes PLK4 expression to promote IAV replication."
MiR-146b-5p.To affects USP3
| 1
MiR-146b-5p.To activates USP3. 1 / 1
| 1

reach
"Regarding the analysis of the results, under the normalization control of renilla luciferase, firefly luciferase was used as the reporter to monitor the regulation of miR-146b-5p.To overexpress Usp3 o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
MiR-146b-5p affects USP3
| 1
MiR-146b-5p decreases the amount of USP3. 1 / 1
| 1

reach
"However, the addition of miR-146b-5p by agomir-146b-5p diminished Usp3- or Sox5 expression ( Fig. 6 E and F)."
MiR-146b-5p inhibitor affects USP3
| 1
MiR-146b-5p inhibitor decreases the amount of USP3. 1 / 1
| 1

reach
"There was no difference in the mRNA levels, although the protein levels of Usp3 or Sox5 in chondrocytes were downregulated by miR-146b-5p mimics and upregulated by miR-146b-5p inhibitor ( Fig. 6 C, D [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
MiR-146-5p affects USP3
| 1
MiR-146-5p activates USP3. 1 / 1
| 1

reach
"Recently, miR-146-5p/USP3 axis was postulated as a possible target for PAH treatment based on the evidence that miR-146-5p promoted hPAECs proliferation under hypoxic conditions through targeting USP3 [30]."
MiR-1245b-5p affects USP3
| 1
USP3 binds miR-1245b-5p. 1 / 1
| 1

reach
"We found that USP3 was highly enriched in Bio-miR-1245b-5p-WT group, and the abundance of USP3 was enhanced after the overexpression of SND1-IT1, indicating the binding between USP3 and miR-1245b-5p is strengthened by SND1-IT1 overexpression (Fig. 4K)."
Methyl methanesulfonate decreases the amount of USP3. 1 / 1
1 |

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

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

No evidence text available
Leptomycin B affects USP3
| 1
| 1

reach
"We found that both LMB treatment and USP3 nucleus export mutation reduced the inhibitory function of USP3 in NF‐κB activation, while the USP3 mutant (the released USP3 in the cytoplasm) maintained a stronger inhibitory function than WT USP3 (Fig 5C and D)."
Ionomycin affects USP3
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Ionomycin decreases the amount of USP3. 1 / 1
1 |

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

No evidence text available
Hsa_circ_0017639 affects USP3
| 1
Hsa_circ_0017639 increases the amount of USP3. 1 / 1
| 1

reach
"56 Similarly, Li et al. show that hsa_circ_0017639 positively regulates USP3 expression by acting as a sponge against miR‐224‐5p, an upstream negative regulator of USP3."
1 |
Hsa-miR-98-5p decreases the amount of USP3. 1 / 1
1 |

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

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

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

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

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

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

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

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

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

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

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

No evidence text available
HoxA affects USP3
| 1
USP3 binds PDS5B and hoxA. 1 / 1
| 1

sparser
"In conclusion, we found an associated lncRNA network that regulates the tumour cell development network, consisting of lncRNA HOXAAS3, miR‐455‐5p and USP3."
Guanine affects USP3
| 1
| 1

reach
"In this study, we found that USP3 was bound with the dynamin-type guanine nucleotide-binding domain (G_DYNAMIN_2) of DNM1L."
Folic acid affects USP3
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Folic acid methylates USP3. 1 / 1
1 |

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

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

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

No evidence text available

reach
"Biochemical assays confirmed that Vitamin B12 effectively suppresses USP3 activity at a level comparable to PR619, a broad-spectrum deubiquitinase inhibitor."
Coumestrol affects USP3
1 |
Coumestrol decreases the amount of USP3. 1 / 1
1 |

No evidence text available
Choline affects USP3
1 |
Choline methylates USP3. 1 / 1
1 |

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

No evidence text available
CarD affects USP3
| 1
| 1

sparser
"Upon viral infection, USP3 directly interacts with the CARD of RIG-I and cleaves the K63-linked polyUb chains, but not the K48-linked polyUb chain, thus converting RIG-I to its inactive form [ xref ]."
1 |
Beta-lapachone increases the amount of USP3. 1 / 1
1 |

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

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

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

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

No evidence text available
| 1
Bafilomycin A1 increases the amount of USP3. 1 / 1
| 1

reach
"Interestingly, bafilomycin A1 treatment significantly enhanced the expression of USP3, both exogenously and endogenously (Fig 5I and J)."
1 |
Arsenous acid increases the amount of USP3. 1 / 1
1 |

No evidence text available
1 |
Antirheumatic drug decreases the amount of USP3. 1 / 1
1 |

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

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

No evidence text available
ZnF-UBP affects USP3
| 1
ZnF-UBP leads to the ubiquitination of USP3. 1 / 1
| 1

reach
"Interestingly, the substitution of a histidine residue within the ZnF-UBP that coordinates zinc abrogated USP3 deubiquitylation activity to the same extent as a substitution of the cysteine in the cat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
ZFAND6 affects USP3
1 |
1 |

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

No evidence text available
Vif affects USP3
| 1
USP3 binds Vif. 1 / 1
| 1

sparser
"Interestingly, we observed that USP3 also interacted with Vif."
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-AS1 affects USP3
| 1
USP3-AS1 activates USP3. 1 / 1
| 1

reach
"We demonstrated that USP3-AS1 increased the stability of USP3 mRNA, resulting in higher USP3 protein expression."
USP3 affects ‐1β
| 1
USP3 inhibits ‐1β. 1 / 1
| 1

reach
"Using USP3‐transfected cells treated with IL‐1β (a ligand for IL‐1R), TNFα (a ligand for TNFR), or 293T‐TLR4 cells treated with LPS (a ligand for TLR4), we showed that USP3 potently inhibited the NF‐κB activation induced by LPS and IL‐1β (Fig 1B)."
USP3 affects γ-H2AX
| 1
USP3 decreases the amount of γ-H2AX. 1 / 1
| 1

reach
"In 2007, Nicassio et al. demonstrated that USP3 deficiency significantly increases the levels of monoubiquitinated H2A (uH2A) and γ-H2AX, resulting in abnormalities in DNA replication and recombination, as well as the accumulation of DNA breaks [90]."
USP3 affects ubiquitination TRAF6
| 1
USP3 inhibits ubiquitination TRAF6. 1 / 1
| 1

eidos
"Moreover , USP3 can reverse the ubiquitination of TRAF6 ( tumor necrosis factor-receptor-associated factor 6 ) , which intermediates the signals from inflammatory cytokines to NF-kappaB activation , thus blocking IL-1beta-induced chondrocyte apoptosis [ 27 ] ."
USP3 affects uH2B protein
| 1
USP3 increases the amount of uH2B protein. 1 / 1
| 1

reach
"The downregulation of USP3 significantly elevates uH2A and uH2B protein levels, leading to functional consequences such as replication stress, abnormal DNA replication and/or recombination, delayed S‐phase progression, accumulation of DNA breaks, and hyperactivation of ATR/ATM‐regulated checkpoint responses."
USP3 affects snail
| 1
USP3 leads to the deubiquitination of snail. 1 / 1
| 1

reach
"USP3 mediates the deubiquitination of snail family transcriptional repressor 1 (SNAIL1)."
USP3 affects signaling
| 1
USP3 inhibits signaling. 1 / 1
| 1

sparser
"Notably, USP3 inhibited signaling by the constitutively active, truncated form of RIG-I (N-RIG-I), but did not inhibit MAVS signaling."
USP3 bound to TRAF6 inhibits signal transduction. 1 / 1
| 1

reach
"We provide the first evidence that USP3 binds directly to TRAF6 and inhibits TRAF6 induced NF-κB signaling pathway activation by ubiquitination in a DUB activity-dependent manner."
USP3 affects sensitized response
| 1
USP3 activates sensitized response. 1 / 1
| 1

eidos
"One possible explanation for this phenotype is that the absence of USP3 could lead to hyper-ubiquitination of H2A and H2B , resulting in a sensitized DNA damage response which eventually leads to genome instability ."

reach
"Since USPs can respond to various stresses and enable cell self-adjustment for survival [40], we speculated that USP3 and USP8 could redistribute metabolic fluxes and induce more energy consumption such as ATP and NADPH to cope with stresses, thereby affecting the secondary metabolism."
| 1
| 1

reach
"USP3 negatively regulates the activation of type 1 interferon (IFN-I) signaling by specifically targeting Retinoic acid-inducible gene I lysine 63(RIG-I K63)-linked polyubiquitin chains and removing them, resulting in IFN-I inhibition."

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."
| 1

sparser
"The two proteins form a nuclear coactivator complex which stimulates transcription of the ubiquitin specific peptidase 3, USP3."
USP3 affects pathogenesis
| 1
| 1

reach
"Furthermore, emerging evidence suggests that USP3 contributes to the pathogenesis of diverse diseases, including inflammation, neurodegeneration, and cancers."
USP3 affects migration
| 1
USP3 activates migration. 1 / 1
| 1

eidos
"Upregulation of USP3 restored MKN-28 and MGC-803 cell proliferation and migration after overexpression of miR-224-5p ."
USP3 affects microRNA-146-5p
| 1
MicroRNA-146-5p binds USP3. 1 / 1
| 1

reach
"In addition, the interaction between microRNA-146-5p and USP3 was examined by luciferase reporting assay."
USP3 affects miR-224-5p
| 1
USP3 activates miR-224-5p. 1 / 1
| 1

reach
"MiR-224-5p downregulation or USP3 overexpression significantly increased USP3 ( Fig. 4 E, F), confirming that USP3 was downstream of miR-224-5p."
USP3 affects miR-1245b-5p
| 1
USP3 binds miR-1245b-5p. 1 / 1
| 1

reach
"We found that USP3 was highly enriched in Bio-miR-1245b-5p-WT group, and the abundance of USP3 was enhanced after the overexpression of SND1-IT1, indicating the binding between USP3 and miR-1245b-5p is strengthened by SND1-IT1 overexpression (Fig. 4K)."
USP3 affects localization
| 1
| 1

reach
"Overexpression of USP3 and USP44 suppresses the localization of 53BP1 to the damage site."
USP3 affects hyper-ubiquitination H2A H2B
| 1
USP3 inhibits hyper-ubiquitination H2A H2B. 1 / 1
| 1

eidos
"One possible explanation for this phenotype is that the absence of USP3 could lead to hyper-ubiquitination of H2A and H2B , resulting in a sensitized DNA damage response which eventually leads to genome instability ."
USP3 affects hsa_circ_0017639
| 1
USP3 increases the amount of hsa_circ_0017639. 1 / 1
| 1

reach
"Upregulation of USP3 or silencing miR-224-5p did not restore or influence hsa_circ_0017639 levels ( Fig. 4 A, B)."
USP3 affects hoxA
| 1
USP3 binds PDS5B and hoxA. 1 / 1
| 1

sparser
"In conclusion, we found an associated lncRNA network that regulates the tumour cell development network, consisting of lncRNA HOXAAS3, miR‐455‐5p and USP3."
USP3 affects histones H2B
| 1
USP3 deubiquitinates histones H2B. 1 / 1
| 1

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 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."
USP3 affects have interaction RIG-I
| 1
USP3 activates have interaction RIG-I. 1 / 1
| 1

eidos
"More specifically , Poly ( I :C ) ( LMW ) stimulation leads USP3 to have a strong interaction with RIG-I , but a weak one with MDA5 , while Poly ( I :C ) ( HMW ) stimulation leads USP3 to have a strong interaction with MDA5 , but a weak one with RIG-I [ 25 ] ."
USP3 affects have interaction MDA5
| 1
USP3 activates have interaction MDA5. 1 / 1
| 1

eidos
"More specifically , Poly ( I :C ) ( LMW ) stimulation leads USP3 to have a strong interaction with RIG-I , but a weak one with MDA5 , while Poly ( I :C ) ( HMW ) stimulation leads USP3 to have a strong interaction with MDA5 , but a weak one with RIG-I [ 25 ] ."
USP3 affects guanine
| 1
| 1

reach
"In this study, we found that USP3 was bound with the dynamin-type guanine nucleotide-binding domain (G_DYNAMIN_2) of DNM1L."
USP3 affects glutathione
| 1
USP3 increases the amount of glutathione. 1 / 1
| 1

reach
"Moreover, USP3 silencing suppressed GSH and GPX4 levels, upregulated iron ion contents, ROS, MDA, and ACSL4 levels, and facilitated ferroptosis."
| 1

reach
"USP3 depletion also led to alterations in glycolysis-related gene expression, which could be partially reversed by MYC overexpression."
USP3 affects ferroptosis
| 1
| 1

reach
"USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis."
USP3 affects deubiquitination snail family transcriptional
| 1
USP3 inhibits deubiquitination snail family transcriptional. 1 / 1
| 1

eidos
"USP3 mediates the deubiquitination of snail family transcriptional repressor 1 ( SNAIL1 ) ."

reach
"Deubiquitinases, including ubiquitin-specific peptidase 3 (USP3), USP21, and CYLD lysine 63 deubiquitinase (CYLD), attenuate the antiviral response by removing the K63-linked polyubiquitin chain."
USP3 affects defects
| 1
USP3 inhibits defects. 1 / 1
| 1

eidos
"Together these observations suggest that knockdown of Usp3 causes defects in replication that cause activation of the ATM / ATR DNA damage response and delays progression though the S-phase ( 157 ) ."
USP3 affects chondrocyte apoptosis induced interleukin IL beta
| 1
USP3 inhibits chondrocyte apoptosis induced interleukin IL beta. 1 / 1
| 1

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

eidos
"Both CCK-8 and EdU assays consistently indicated that USP3 knockdown markedly reduced the proliferation of HCC cells ( P < 0.05 , Figures 2B , C ) ."
USP3 affects carD
| 1
| 1

sparser
"Upon viral infection, USP3 directly interacts with the CARD of RIG-I and cleaves the K63-linked polyUb chains, but not the K48-linked polyUb chain, thus converting RIG-I to its inactive form [ xref ]."
USP3 affects ZFAND6
1 |
1 |

No evidence text available
USP3 affects XRCC1
| 1
USP3 inhibits XRCC1. 1 / 1
| 1

reach
"In conclusion, we authenticated that USP3 suppressed RCC progression and was regulated by ELF5."
| 1

eidos
"Moreover , the loss of USP3 promoted the ubiquitination and weakened the stability of PKLR ."
USP3 affects USP16
| 1
| 1

sparser
"Both USP3 and USP16 are also associated with H2A deubiquitination following DNA damage processing [ xref , xref ]."
USP3 affects UMOD
| 1
USP3 activates UMOD. 1 / 1
| 1

reach
"Although we observed the existence of cytoplasmic USP3 even without LPS stimulation in USP3‐expressing THP‐1 cells, possibly due to the overexpression of USP3, LPS pretreatment still increased the amount of cytoplasmic USP3 in these cells (Fig EV5C), indicating that LPS‐pretreatment induces the cytoplasmic retention of both endogenous and exogenous USP3 in THP‐1 cells."
USP3 affects UCH
| 1
USP3 activates UCH. 1 / 1
| 1

reach
"We next examined the effect of USP3 on mRNA levels of A3G and found that USP3 upregulated mRNA levels of endogenous A3G in HepG2 cells, even in ZNF and UCH (with weaker ability to increase A3G mRNA) truncated mutants, explaining the reason why ZNF increased A3G expression."
USP3 affects TXLNG
1 |
1 |

No evidence text available
USP3 affects TRIM69
| 1
USP3 deubiquitinates TRIM69. 1 / 1
| 1

reach
"For example, TNFAIP3, CYLD, USP3, USP4, USP15, USP25, and OTUD5 deubiquitinate key components of the IFN production pathway, including RIG-I, TRAF2, TRAF3, TRAF6, RIP1, and TRIF (reviewed in [93,94])."
USP3 affects TRAF3
| 1
USP3 deubiquitinates TRAF3. 1 / 1
| 1

reach
"For example, TNFAIP3, CYLD, USP3, USP4, USP15, USP25, and OTUD5 deubiquitinate key components of the IFN production pathway, including RIG-I, TRAF2, TRAF3, TRAF6, RIP1, and TRIF (reviewed in [93,94])."
USP3 affects TOR1AIP2
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1 |

No evidence text available
USP3 affects TNMs to 31.1 ± 2.3 mg/L
| 1
USP3 activates TNMs to 31.1 ± 2.3 mg/L. 1 / 1
| 1

reach
"In contrast, the overexpression of usp3 significantly increased the titer of TNMs to 31.1 ± 2.3 mg/L (Fig. 2b)."
USP3 affects TIR
| 1
| 1

sparser
"To determine the interaction domain of MyD88 with USP3, we generated two deletion mutants containing MyD88 death domain (DD) or MyD88 Toll‐interleukin 1 receptor domain (TIR), respectively, and found that both the TIR and DD domains could interact with USP3."
USP3 affects TGFB
| 1
USP3 activates TGFB. 1 / 1
| 1

reach
"USP3, which is induced by transforming growth factor-beta 1 (TGF-β1), facilitates the migration and invasion of GC cells by enhancing the deubiquitination and stability of suppressor of Zeste 12 homolog (SUZ12)14."
USP3 affects TEAD4
1 |
1 |

No evidence text available
USP3 affects SRSF1
| 1
USP3 binds SRSF1 and RIGI. 1 / 1
| 1

sparser
"To examine which proteins directly interact with RIG-I, we transfected 293T cells with HA-tagged candidate genes together with Flag-tagged RIG-I. Coimmunoprecipitation and western blot analyses revealed that USP3 and SRSF1 specifically interact with RIG-I in vitro ( xref and xref )."
USP3 affects SND1-IT1
| 1
USP3 increases the amount of SND1-IT1. 1 / 1
| 1

reach
"Lastly, SND1-IT1 is significantly overexpressed in GC cell-secreted exosomes and promotes malignant transformation of GES-1 by increasing USP3 expression and mediating deubiquitination of SNAIL1 (Jin et al., 2022)."
USP3 affects SNAI2
| 1
USP3 increases the amount of SNAI2. 1 / 1
| 1

reach
"The deubiquitinases USP9X, USP21, and USP3 have been found to promote the MES transformation of GBM by stabilizing the expression of ALDH1A3, FOXD1, and Snail2, respectively, in the MES phenotype."
USP3 affects SH3BGRL3
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1 |

No evidence text available
USP3 affects SEC23
| 1
USP3 deubiquitinates SEC23. 1 / 1
| 1

reach
"Interestingly, other data show that Sec23 is ubiquitylated by Rsp5 and de-ubiquitylated by Usp3/Bre5, with the ubiquitylated form of Sec23 unable to interact with Sec24."
USP3 affects SACS
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1 |

No evidence text available
USP3 affects S phase
| 1
USP3 activates S phase. 1 / 1
| 1

reach
"RNAi-mediated ablation of USP3 leads to the accumulation of DNA breakage and thus replication stress by delaying progression of the S-phase during cell division [239]."
USP3 affects RNF4
1 |
1 |

No evidence text available
| 1

reach
"RNA binding motif 4 (RBM4), responsible for gene splicing, is negatively regulated by USP3 at both the protein and mRNA levels."
USP3 affects RLR
| 1
USP3 binds RLR and Caspase. 1 / 1
| 1

sparser
"We further show that there is no interaction between USP3 and RIG-I-like receptors (RLRs) in unstimulated or uninfected cells, but upon viral infection or ligand stimulation, USP3 binds to the caspase activation recruitment domain of RLRs and then cleaves polyubiquitin chains through cooperation of its zinc-finger Ub-binding domain and USP catalytic domains."
USP3 affects RIPK1
| 1
USP3 deubiquitinates RIPK1. 1 / 1
| 1

reach
"For example, TNFAIP3, CYLD, USP3, USP4, USP15, USP25, and OTUD5 deubiquitinate key components of the IFN production pathway, including RIG-I, TRAF2, TRAF3, TRAF6, RIP1, and TRIF (reviewed in [93,94])."
USP3 affects RIMBP2
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1 |

No evidence text available
USP3 affects RIG-I-MAVS
| 1
USP3 inhibits RIG-I-MAVS. 1 / 1
| 1

reach
"In contrast to those of TRIM25 and ZCCHC3, the ubiquitin carboxyl-terminal hydrolase CYLD, USP3 (ubiquitin-specific peptidase 3) and USP21 negatively regulate RIG-I-MAVS signaling by removing K63-linked polyubiquitin chains (71–73)."
USP3 affects RBPs
| 1
RBPs binds USP3. 1 / 1
| 1

reach
"The RBPs (TARDBP, DDX54 and HNRNPC) which can bind to both SND1-IT1 and USP3 were predicted by starBase under the condition of Pan-Cancer ≥ 15, ClusterNum ≥ 30 and ClipExpNum ≥ 5 (Fig. 5A)."
USP3 affects RASGRP3
| 1
USP3 increases the amount of RASGRP3. 1 / 1
| 1

reach
"USP3 promotes transcription of RASGRP3 by deubiquitinating and stabilizing the transcription factor AR, and up-regulation of RASGRP3 increases CRC sensitivity to oxaliplatin [69]."
USP3 affects PRRC2B
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1 |

No evidence text available
USP3 affects PDS5B
| 1
USP3 binds PDS5B and hoxA. 1 / 1
| 1

sparser
"In conclusion, we found an associated lncRNA network that regulates the tumour cell development network, consisting of lncRNA HOXAAS3, miR‐455‐5p and USP3."
USP3 affects PARP1
| 1
USP3 inhibits PARP1. 1 / 1
| 1

reach
"Importantly, inhibition and/or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1 -/- cells, highlighting PARP1 and USP3 as possible therapeutic targets in neurological disease."
USP3 affects OTULIN
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1 |

No evidence text available
USP3 affects MYCN protein stability
| 1
USP3 activates MYCN protein stability. 1 / 1
| 1

eidos
"We show that increased USP3 levels reduce K-48 - and K-63-linked ubiquitination of MYCN , thus driving up MYCN protein stability ."
USP3 affects MMP13
| 1
USP3 decreases the amount of MMP13. 1 / 1
| 1

reach
"Consistent with previous reports, this study showed that both IL-1β induction and knockdown of USP3 could increase MMP-1/MMP-13 expression, while overexpression of USP3 could block IL-1β effects on MM[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 affects MMP1
| 1
USP3 decreases the amount of MMP1. 1 / 1
| 1

reach
"Consistent with previous reports, this study showed that both IL-1β induction and knockdown of USP3 could increase MMP-1/MMP-13 expression, while overexpression of USP3 could block IL-1β effects on MM[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP3 affects MKN-28 MGC-803 cell
| 1
USP3 activates MKN-28 MGC-803 cell. 1 / 1
| 1

eidos
"Upregulation of USP3 restored MKN-28 and MGC-803 cell proliferation and migration after overexpression of miR-224-5p ."
USP3 affects MCL1
| 1
USP3 deubiquitinates MCL1. 1 / 1
| 1

reach
"Wu et al. found that the deubiquitinating enzyme 3 (DUB3) in the cytoplasm of OC cells interacts with and deubiquitinates MCL1, thereby protecting MCL1 from degradation."
USP3 affects MAPK
| 1
USP3 leads to the dephosphorylation of MAPK. 1 / 1
| 1

reach
"We next sought to determine whether the enhanced IKK, IκBα, and MAPK phosphorylation caused by USP3 deficiency promotes NF‐κB‐dependent gene expression."
| 1

reach
"These results demonstrate that Usp3 deficiency severely disrupts the establishment of normal endotoxin tolerance and dramatically increases proinflammatory cytokine release upon endo toxin challenge."
USP3 affects K882
| 1
USP3 binds EPHA2 and K882. 1 / 1
| 1

reach
"Moreover, R203 of USP3 was important during the interaction between USP3 and EPHA2, and K882 and K945 of EPHA2 were the key ubiquitination sites regulated by USP3."
USP3 affects K-63-linked ubiquitination MYCN
| 1
USP3 inhibits K-63-linked ubiquitination MYCN. 1 / 1
| 1

eidos
"We show that increased USP3 levels reduce K-48 - and K-63-linked ubiquitination of MYCN , thus driving up MYCN protein stability ."
USP3 affects K-48
| 1
USP3 inhibits K-48. 1 / 1
| 1

eidos
"We show that increased USP3 levels reduce K-48 - and K-63-linked ubiquitination of MYCN , thus driving up MYCN protein stability ."
USP3 affects IL6
| 1
USP3 decreases the amount of IL6. 1 / 1
| 1

reach
"The IL-6 levels in cell culture supernatant from primary chondrocytes were significantly increased due to miR-146b-5p mimics treatment but decreased by the overexpression of Usp3."
USP3 affects IL-1beta-mediated chondrocyte senescence
| 1
USP3 inhibits IL-1beta-mediated chondrocyte senescence. 1 / 1
| 1

eidos
"This study demonstrated that USP3 probably attenuated IL-1beta-mediated chondrocyte senescence by deacetylating FOXO3 via SIRT3 ."
USP3 affects IL-1beta-induced chondrocyte apoptosis
| 1
USP3 inhibits IL-1beta-induced chondrocyte apoptosis. 1 / 1
| 1

eidos
"Moreover , USP3 can reverse the ubiquitination of TRAF6 ( tumor necrosis factor-receptor-associated factor 6 ) , which intermediates the signals from inflammatory cytokines to NF-kappaB activation , thus blocking IL-1beta-induced chondrocyte apoptosis [ 27 ] ."
USP3 affects IKK_complex
| 1
USP3 leads to the dephosphorylation of IKK_complex. 1 / 1
| 1

reach
"We next sought to determine whether the enhanced IKK, IκBα, and MAPK phosphorylation caused by USP3 deficiency promotes NF‐κB‐dependent gene expression."
USP3 affects IKBKB
| 1
USP3 deubiquitinates IKBKB. 1 / 1
| 1

reach
"Furthermore, USP3 enhances Ikbkb protein levels by deubiquitinating Ikbkb."
USP3 affects Histone_H2A
| 1
USP3 deubiquitinates Histone_H2A on K13. 1 / 1
| 1

trips
"USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15."
USP3 affects HNRNPL
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1 |

No evidence text available
USP3 affects H4C16
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1 |

No evidence text available
USP3 affects H3C12
1 |
1 |

No evidence text available
USP3 affects H2BK120ub
| 1
USP3 deubiquitinates H2BK120ub. 1 / 1
| 1

reach
"Other major DUBs with specificity for histone H2AK119ub over H2BK120ub are BAP1 and USP16, while USP3, USP12, USP22, and USP44 deubiquitinate both H2AK119ub and H2BK120ub, as well as different non histone substrates [XREF_BIBR]."
USP3 affects H2BC3
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1 |

No evidence text available
USP3 affects H2BC10
1 |
USP3 deubiquitinates H2BC10. 1 / 1
1 |

"Here we identify the ubiquitin-specific protease 3 <span class="match term0">USP3</span> as a deubiquitinating enzyme for uH2A and u<span class="match term1">H2B</span>"
USP3 affects 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 H2AK13/15ub
| 1
USP3 deubiquitinates H2AK13/15ub. 1 / 1
| 1

reach
"USP3 deubiquitinates H2AK13/15ub as well as H2A119ub in response to DNA damage and affects recruitment of 53BP1 in cells [19,46]."
USP3 affects H2AK119ub
| 1
USP3 deubiquitinates H2AK119ub. 1 / 1
| 1

reach
"Other major DUBs with specificity for histone H2AK119ub over H2BK120ub are BAP1 and USP16, while USP3, USP12, USP22, and USP44 deubiquitinate both H2AK119ub and H2BK120ub, as well as different non histone substrates [XREF_BIBR]."
USP3 affects H2AC8
1 |
1 |

No evidence text available

reach
"Depletion of USP3 leads to prolonged CHK1 checkpoint activation, promoting cell resistance to cell death induced by hydroxyurea (HU), and enhancing genome stability."
USP3 affects GLI2
| 1
| 1

sparser
"Smoothened positively regulates USP3 gene transcription by facilitating Gli2 binding to the USP3 promoter region, specifically at positions −1355 to −1344."
USP3 affects GBM progress
| 1
USP3 activates GBM progress. 1 / 1
| 1

eidos
"27 , 28 Recent studies have proven that USP3 promotes GBM progress by regulating the EMT process ."
USP3 affects FUT1
| 1
| 1

sparser
"In agreement with the enhanced DNA breaks in MEFs, USP3 loss was further associated with spontaneous DNA damage in HSCs in vivo and in vitro."
USP3 affects FOXD1
| 1
USP3 increases the amount of FOXD1. 1 / 1
| 1

reach
"The deubiquitinases USP9X, USP21, and USP3 have been found to promote the MES transformation of GBM by stabilizing the expression of ALDH1A3, FOXD1, and Snail2, respectively, in the MES phenotype."
USP3 affects FBXL22
| 1
| 1

sparser
"The PRL and SOX4 protein-coding genes are associated with CASC15 , PPP1R26 is associated with PPP1R26-AS1 , and USP3 and FBXL22 are associated with USP3-AS1 ."
USP3 affects ESR2
1 |
1 |

No evidence text available
USP3 affects ELAVL1
1 |
1 |

No evidence text available
USP3 affects EIF4G1
1 |
1 |

No evidence text available
USP3 affects EIF3I
1 |
1 |

No evidence text available
USP3 affects EIF3G
1 |
1 |

No evidence text available
USP3 affects EIF3D
1 |
1 |

No evidence text available
USP3 affects EIF3C
1 |
1 |

No evidence text available
USP3 affects EIF3B
1 |
1 |

No evidence text available
USP3 affects EIF3A
1 |
1 |

No evidence text available

reach
"USP3 promotes DNA damage response and chemotherapy resistance through stabilizing and deubiquitinating SMARCA5 in prostate cancer."
USP3 affects DIRAS1
| 1
USP3 inhibits DIRAS1. 1 / 1
| 1

reach
"USP3, USP21 and CYLD inhibit RIG‐I K63‐linked ubiquitination and activation."
USP3 affects DHX15
1 |
1 |

No evidence text available
USP3 affects Cyclin
| 1
USP3 activates Cyclin. 1 / 1
| 1

reach
"49 Their findings indicate that USP3 overexpression accelerates GC cell proliferation by promoting G1–S transition and upregulating cyclins D and E."
USP3 affects Cui et al., 2014
| 1
USP3 activates Cui et al., 2014. 1 / 1
| 1

reach
"For example, ubiquitin-specific peptidase 3 (USP3), USP21, and cylindromatosis lysine 63 deubiquitinase (CYLD) modulate RIG-I signaling by removing K63-polyubiquitin chains (Cui et al., 2014; Fan et al., 2014)."
| 1
| 1

reach
"Nagy et al. reported that USP3 promotes neuroblastoma cell viability, proliferation, and xenograft tumor growth by cleaving K48‐ and K63‐linked ubiquitin chains of MYCN (Figure 2C, right)."
USP3 affects Cdc25A protein
| 1
USP3 activates Cdc25A protein. 1 / 1
| 1

eidos
"USP3 depletion reduces the Cdc25A protein level , resulting in a significant delay in cell-cycle progression , and reduces the growth of cervical tumor xenografts in nude mice ."
USP3 affects Caspase
| 1
USP3 binds RLR and Caspase. 1 / 1
| 1

sparser
"We further show that there is no interaction between USP3 and RIG-I-like receptors (RLRs) in unstimulated or uninfected cells, but upon viral infection or ligand stimulation, USP3 binds to the caspase activation recruitment domain of RLRs and then cleaves polyubiquitin chains through cooperation of its zinc-finger Ub-binding domain and USP catalytic domains."
USP3 affects CTNNB1
| 1
USP3 increases the amount of CTNNB1. 1 / 1
| 1

reach
"Pearson correlation coefficient analysis revealed a strong positive correlation between USP3 and CTNNB1, and consistently, USP3 knockdown reduced the levels and activities of β-catenin in HCC cells."
USP3 affects CDKN1A
| 1
USP3 decreases the amount of CDKN1A. 1 / 1
| 1

reach
"We found that overexpression of wildtype USP3 in the knockdown cells rescued the protein level of p53 in both cell lines, and accordingly increased p21 protein level."
USP3 affects CD58
| 1
USP3 inhibits CD58. 1 / 1
| 1

reach
"While it promotes infection through the inhibition of the type I interferon signaling pathway, 35 , 72 Zhao et al. presented contrasting evidence, indicating that USP3 inhibits HIV replication by enhancing the host defensive factor AG3."
USP3 affects CBR3
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1 |

No evidence text available
USP3 affects CARD
| 1
| 1

reach
"Upon viral infection, USP3 directly interacts with the CARD of RIG-I and cleaves the K63 linked polyUb chains, but not the K48 linked polyUb chain, thus converting RIG-I to its inactive form [XREF_BIBR]."
USP3 affects CARD domain
| 1
USP3 binds polyubiquitin chains and CARD domain. 1 / 1
| 1

reach
"[164] Upon viral infection or ligand stimulation, USP3 binds to the CARD domain of RIG-I and then removes its polyubiquitin chains through both the zinc-finger Ub binding domain and USP catalytic domains."
USP3 affects CALM1
| 1
| 1

sparser
"To determine which SVBV-encoded protein was a translation trans-activator, we cloned individual SVBV-US ORFs into the pCAM-2300 vector to produce pCAM-USP1, pCAM-USP2, pCAM-USP3, pCAM-USP4, pCAM-USP5, and pCAM-USP6."
USP3 affects BAP1
| 1
BAP1 binds USP3 and KLF5. 1 / 1
| 1

sparser
"Both BAP1 and USP3 bind to and stabilize KLF5 via deubiquitination [ xref , xref ], indicating the possible regulatory role of DUBs in cancer proliferation."
USP3 affects Aurora A
| 1
USP3 deubiquitinates Aurora A. 1 / 1
| 1

reach
"Elevated levels of USP3 and Aurora A, both of which are deubiquitinated by USP3, have been observed in ESCC and are associated with increased cell proliferation, invasion, and metastasis [62]."
USP3 affects ATR-CHK1
| 1
USP3 activates ATR-CHK1. 1 / 1
| 1

reach
"Additionally, the UCH domain of USP3 interacts with the N-terminus of Claspin, stabilizing it against ubiquitination and consequently activating ATR-CHK1 signaling, which contributes to the radioresistance in GBM cells [243]."
USP3 affects ATP6V1H
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1 |

No evidence text available
USP3 affects ALDH1A3
| 1
USP3 increases the amount of ALDH1A3. 1 / 1
| 1

reach
"The deubiquitinases USP9X, USP21, and USP3 have been found to promote the MES transformation of GBM by stabilizing the expression of ALDH1A3, FOXD1, and Snail2, respectively, in the MES phenotype."
USP3 affects AFF4
| 1
USP3 inhibits AFF4. 1 / 1
| 1

reach
"In contrast, no significant change in Pol II occupancy signals was detected upon AFF4 knockdown in Cluster 2 genes, such as RPL31 and USP3, which exhibited weak and sharp AFF4 binding (<3 kb) (Figure 2D and E)."
USP3 affects AC092894.1
| 1
AC092894.1 binds USP3. 1 / 1
| 1

reach
"This further demonstrated the binding of AC092894.1 to USP3 (Fig. 6G)."
USP3 affects PGL3-USP3 3'UTR
| 1
USP3 activates PGL3-USP3 3'UTR. 1 / 1
| 1

reach
"Similarly, overexpression of USP3 or SMAD4 3 ' UTR led to significantly increased activities on the PGL3-USP3 3 ' UTR and PGL3-SMAD4 3 ' UTR reporter constructs."
USP3 affects PGL3-SMAD4 3'UTR reporter constructs
| 1
USP3 activates PGL3-SMAD4 3'UTR reporter constructs. 1 / 1
| 1

reach
"Similarly, overexpression of USP3 or SMAD4 3 ' UTR led to significantly increased activities on the PGL3-USP3 3 ' UTR and PGL3-SMAD4 3 ' UTR reporter constructs."
USP16 affects USP3
| 1
| 1

sparser
"Both USP3 and USP16 are also associated with H2A deubiquitination following DNA damage processing [ xref , xref ]."
USP11 affects USP3
| 1
USP11 deubiquitinates USP3. 1 / 1
| 1

reach
"Similarly, ubiquitin-processing proteases, such as ubiquitin-specific-processing protease 11 (USP11) and deubiquitinating enzyme 3 (DUB3), catalyze the removal of ubiquitin from NRF2, thereby stabilizing NRF2 protein [34,35]."
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]"
UBC affects RIGI
| 1
UBC binds USP3 and RIGI. 1 / 1
| 1

sparser
"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63-linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [ xref ], we focused on SRSF1 for further experiments."
TXLNG affects USP3
1 |
1 |

No evidence text available
TP53BP1 affects USP3
1 |
1 |

No evidence text available
TOR1AIP2 affects USP3
1 |
1 |

No evidence text available
TIR affects USP3
| 1
| 1

sparser
"To determine the interaction domain of MyD88 with USP3, we generated two deletion mutants containing MyD88 death domain (DD) or MyD88 Toll‐interleukin 1 receptor domain (TIR), respectively, and found that both the TIR and DD domains could interact with USP3."
TGM1 affects USP3
| 1
TGM1 decreases the amount of USP3. 1 / 1
| 1

reach
"68 Li et al. 78 report that PM2.5 can inhibit USP3 expression in mRNA and protein levels, resulting in pulmonary inflammation.In summary, lncRNAs and circular RNAs predominantly act as positive regulators of USP3 expression, whereas miRNAs typically serve as negative regulators."
TEAD4 affects USP3
1 |
1 |

No evidence text available
STING1 affects USP3
1 |
1 |

No evidence text available
SRSF1 affects USP3
| 1
USP3 binds SRSF1 and RIGI. 1 / 1
| 1

sparser
"To examine which proteins directly interact with RIG-I, we transfected 293T cells with HA-tagged candidate genes together with Flag-tagged RIG-I. Coimmunoprecipitation and western blot analyses revealed that USP3 and SRSF1 specifically interact with RIG-I in vitro ( xref and xref )."
SP1 affects USP3
1 |
SP1 decreases the amount of USP3. 1 / 1
1 |

No evidence text available
SND1 affects USP3
| 1
SND1 increases the amount of USP3. 1 / 1
| 1

reach
"77 Jin et al. 52 found that the mRNA level of USP3 is significantly upregulated by lncRNA SND1‐IT1 overexpression and decreased by miR‐1245b‐5p overexpression."
SIRT3 affects USP3
| 1
SIRT3 activates USP3. 1 / 1
| 1

reach
"Consistently, suppression of SIRT3 attenuated the function of USP3 upregulation in cell senescence in rat chondrocytes (98)."
SH3BGRL3 affects USP3
1 |
1 |

No evidence text available
SACS affects USP3
1 |
1 |

No evidence text available
RNF4 affects USP3
1 |
1 |

No evidence text available
RNA helicase affects USP3
| 1
RNA helicase bound to miR-1245b-5p increases the amount of USP3. 1 / 1
| 1

reach
"In addition, Jin et al. demonstrated that exosomal lncRNA SND1-IT1 secreted from GC cells not only recruited DDX54, a DEAD-box RNA helicase that binds to specific RNAs, to enhance USP3 mRNA stability, but also bound to miR-1245b-5p to upregulate USP3 expression, thus leading to SNAIL1 stabilization and inducing the malignant transformation of gastric mucosa cells [24]."
RLR affects USP3
| 1
USP3 binds RLR and Caspase. 1 / 1
| 1

sparser
"We further show that there is no interaction between USP3 and RIG-I-like receptors (RLRs) in unstimulated or uninfected cells, but upon viral infection or ligand stimulation, USP3 binds to the caspase activation recruitment domain of RLRs and then cleaves polyubiquitin chains through cooperation of its zinc-finger Ub-binding domain and USP catalytic domains."
RIMBP2 affects USP3
1 |
1 |

No evidence text available
RIGI affects UBC, and USP3
| 1
UBC binds USP3 and RIGI. 1 / 1
| 1

sparser
"Because it was recently shown that USP3 interacts with RIG-I to deubiquitinate K63-linked poly-ubiquitin chains on RIG-I and inhibit type I IFN pathways [ xref ], we focused on SRSF1 for further experiments."
RIGI affects SRSF1, and USP3
| 1
USP3 binds SRSF1 and RIGI. 1 / 1
| 1

sparser
"To examine which proteins directly interact with RIG-I, we transfected 293T cells with HA-tagged candidate genes together with Flag-tagged RIG-I. Coimmunoprecipitation and western blot analyses revealed that USP3 and SRSF1 specifically interact with RIG-I in vitro ( xref and xref )."
RBPs affects USP3
| 1
RBPs binds USP3. 1 / 1
| 1

reach
"The RBPs (TARDBP, DDX54 and HNRNPC) which can bind to both SND1-IT1 and USP3 were predicted by starBase under the condition of Pan-Cancer ≥ 15, ClusterNum ≥ 30 and ClipExpNum ≥ 5 (Fig. 5A)."
RBPMS2 affects USP3
| 1
RBPMS2 decreases the amount of USP3. 1 / 1
| 1

reach
"Among SNPs at the locus with P < 1 × 10 , many have been reported as cis-eQTLs in whole blood and other tissues with febrile seizures risk alleles corresponding to decreased expression of HERC1, USP3, DAPK2 and PLEKHO2, and increased expression of FBXL22, APH1B and RBPMS2 (Supplementary Table 5)."

reach
"Recently, miR-146-5p/USP3 axis was postulated as a possible target for PAH treatment based on the evidence that miR-146-5p promoted hPAECs proliferation under hypoxic conditions through targeting USP3 [30]."
Protease affects USP3
| 1
Protease deubiquitinates USP3. 1 / 1
| 1

reach
"Very recently, ovarian tumor protease (OTU) deubiquitinating enzyme 3 (OTUD3), a deubiquitination enzyme, was reported to bind to MDA5 and RIG-I and ultimately remove their Lys-63-linked polyubiquitination to diminish the signal transduction of RLRs, thus inhibiting the antiviral immune response against RNA viruses (Figure 2) [108]."
Poly :C affects USP3
| 1
Poly :C activates USP3. 1 / 1
| 1

eidos
"More specifically , Poly ( I :C ) ( LMW ) stimulation leads USP3 to have a strong interaction with RIG-I , but a weak one with MDA5 , while Poly ( I :C ) ( HMW ) stimulation leads USP3 to have a strong interaction with MDA5 , but a weak one with RIG-I [ 25 ] ."
Poly :C HMW affects USP3
| 1
Poly :C HMW activates USP3. 1 / 1
| 1

eidos
"More specifically , Poly ( I :C ) ( LMW ) stimulation leads USP3 to have a strong interaction with RIG-I , but a weak one with MDA5 , while Poly ( I :C ) ( HMW ) stimulation leads USP3 to have a strong interaction with MDA5 , but a weak one with RIG-I [ 25 ] ."
1 |
Particulate Matter decreases the amount of USP3. 1 / 1
1 |

No evidence text available
PRRC2B affects USP3
1 |
1 |

No evidence text available
PM2.5 affects USP3
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PM2.5 decreases the amount of USP3. 1 / 1
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"68 Li et al. 78 report that PM2.5 can inhibit USP3 expression in mRNA and protein levels, resulting in pulmonary inflammation.In summary, lncRNAs and circular RNAs predominantly act as positive regulators of USP3 expression, whereas miRNAs typically serve as negative regulators."
PDS5B affects hoxA
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USP3 binds PDS5B and hoxA. 1 / 1
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"In conclusion, we found an associated lncRNA network that regulates the tumour cell development network, consisting of lncRNA HOXAAS3, miR‐455‐5p and USP3."
OTULIN affects USP3
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No evidence text available
OTU affects USP3
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OTU deubiquitinates USP3. 1 / 1
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"Very recently, ovarian tumor protease (OTU) deubiquitinating enzyme 3 (OTUD3), a deubiquitination enzyme, was reported to bind to MDA5 and RIG-I and ultimately remove their Lys-63-linked polyubiquitination to diminish the signal transduction of RLRs, thus inhibiting the antiviral immune response against RNA viruses (Figure 2) [108]."
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Neuroblastoma increases the amount of USP3. 1 / 1
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"In neuroblastoma patients, the m C reader ALYREF forms a nuclear coactivator complex with MYCN to stimulate USP3 transcription, which promotes the tumorigenesis of neuroblastoma (89)."
Neoplasms affects USP3
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Neoplasms increases the amount of USP3. 1 / 1
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"The results indicated that tumor volume and size significantly increased with USP3 overexpression, while they decreased with USP3 knockdown."
NR1H4 affects USP3
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NR1H4 decreases the amount of USP3. 1 / 1
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No evidence text available
NANOG affects USP10, USP16, USP3, USP37, USP44, and USP7
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"USP25, USP44, USP49, and USP7 bind to the Sox2 promoter, while USP10, USP16, USP3, USP37, USP44, and USP7 bind to the Nanog promoter."
MicroRNAs affects USP3
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MicroRNAs decreases the amount of USP3. 1 / 1
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"72 Zhang et al. revealed that miR‐146‐5p overexpression reduces the mRNA and protein levels of USP3 in a human pulmonary artery endothelial cell line under hypoxic conditions."
MYOD1 affects USP3
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MYOD1 decreases the amount of USP3. 1 / 1
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No evidence text available
MYCN affects ALYREF
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ALYREF binds USP3 and MYCN. 1 / 1
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"The ALYREF-USP3-MYCN complex is a potential therapeutic target for NB by exploiting obligatory ALYREF dependence in MYCN-amplified cells [37]."
L-methionine affects USP3
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No evidence text available
KLF5 affects BAP1
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BAP1 binds USP3 and KLF5. 1 / 1
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"Both BAP1 and USP3 bind to and stabilize KLF5 via deubiquitination [ xref , xref ], indicating the possible regulatory role of DUBs in cancer proliferation."
K882 affects USP3
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USP3 binds EPHA2 and K882. 1 / 1
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"Moreover, R203 of USP3 was important during the interaction between USP3 and EPHA2, and K882 and K945 of EPHA2 were the key ubiquitination sites regulated by USP3."
K63 affects polyubiquitin
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Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
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"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
IFIH1 affects USP3, and polyubiquitin
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USP3 binds polyubiquitin and IFIH1. 1 / 1
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"USP3 may bind to MDA5 via unanchored polyUb chains and then deubiquitinate it [ xref ]."
IFIH1 affects K63, USP3, and polyubiquitin
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Polyubiquitin binds K63, USP3, and IFIH1. 1 / 1
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"In addition to RIG-I, USP3 also binds MDA5 to remove K63-polyubiquitin chains on the N-terminal CARDs [ xref ]."
Hsa_circ_0017639 affects USP3
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Hsa_circ_0017639 increases the amount of USP3. 1 / 1
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"Hsa_circ_0017639, a circular RNA, is increased in GC cell lines and promotes proliferation and migration by increasing USP3 expression by sponging miR-224-5p [23]."
Histone_H2B affects USP3
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"In the DDR, USP3 dynamically interacts with chromatin and deubiquitinates H2A and H2B."
HOXA-AS3 affects USP3
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HOXA-AS3 increases the amount of USP3. 1 / 1
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"It has been reported that HOXA-AS3 increases USP3 expression via sponging of miR-455–5p to promote EMT [82] ."
HNRNPL affects USP3
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No evidence text available
HDX affects USP3
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HDX activates USP3. 1 / 1
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"In the USP5 structure, there is a close π-stacking interaction between the pyridine moieties of ZQ1 and Y259, which is analogous to the HDX-supported 59/USP3 Y94 interaction discussed above.Compound 59 binds USP3 with a K of around 14 μM, which would not be sufficient for a traditional occupancy-based competitor."
H4C16 affects USP3
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No evidence text available
H3C12 affects USP3
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No evidence text available
H2BC3 affects USP3
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No evidence text available
H2AC8 affects USP3
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No evidence text available
H2AC20 affects USP16, and USP3
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"Both USP3 and USP16 are also associated with H2A deubiquitination following DNA damage processing [ xref , xref ]."
Gentamicins affects USP3
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Gentamicins decreases the amount of USP3. 1 / 1
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No evidence text available
GLI2 affects USP3
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"Smoothened positively regulates USP3 gene transcription by facilitating Gli2 binding to the USP3 promoter region, specifically at positions −1355 to −1344."
FUT1 affects USP3
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"In agreement with the enhanced DNA breaks in MEFs, USP3 loss was further associated with spontaneous DNA damage in HSCs in vivo and in vitro."
FOXF2 affects USP3
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FOXF2 decreases the amount of USP3. 1 / 1
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No evidence text available
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Enterolactone decreases the amount of USP3. 1 / 1
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No evidence text available
ESRRA affects USP3
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ESRRA decreases the amount of USP3. 1 / 1
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No evidence text available
ESR2 affects USP3
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No evidence text available
EPHA2 affects K882, and USP3
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USP3 binds EPHA2 and K882. 1 / 1
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"Moreover, R203 of USP3 was important during the interaction between USP3 and EPHA2, and K882 and K945 of EPHA2 were the key ubiquitination sites regulated by USP3."
ELAVL1 affects USP3
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No evidence text available
EIF4G1 affects USP3
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No evidence text available
EIF3I affects USP3
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No evidence text available
EIF3G affects USP3
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No evidence text available
EIF3D affects USP3
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No evidence text available
EIF3C affects USP3
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No evidence text available
EIF3B affects USP3
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No evidence text available
EIF3A affects USP3
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No evidence text available
DHX15 affects USP3
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No evidence text available
Caspase affects USP3
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USP3 binds RLR and Caspase. 1 / 1
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"We further show that there is no interaction between USP3 and RIG-I-like receptors (RLRs) in unstimulated or uninfected cells, but upon viral infection or ligand stimulation, USP3 binds to the caspase activation recruitment domain of RLRs and then cleaves polyubiquitin chains through cooperation of its zinc-finger Ub-binding domain and USP catalytic domains."
CD163 affects USP3
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CD163 deubiquitinates USP3. 1 / 1
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"Extensive immunoreactivity of CD163, scavenger receptor class B, member 1 (SRBI) and deubiquitinating enzyme 3 (Dub3) was a prominent feature of DSCLs compared to both NAWM from lesional cases and control WM from non-lesional cases."
CBR3 affects USP3
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No evidence text available
CARD affects USP3
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"Upon viral infection, USP3 directly interacts with the CARD of RIG-I and cleaves the K63 linked polyUb chains, but not the K48 linked polyUb chain, thus converting RIG-I to its inactive form [XREF_BIBR]."
CARD domain affects polyubiquitin chains
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USP3 binds polyubiquitin chains and CARD domain. 1 / 1
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"[164] Upon viral infection or ligand stimulation, USP3 binds to the CARD domain of RIG-I and then removes its polyubiquitin chains through both the zinc-finger Ub binding domain and USP catalytic domains."
CALM1 affects USP3
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"To determine which SVBV-encoded protein was a translation trans-activator, we cloned individual SVBV-US ORFs into the pCAM-2300 vector to produce pCAM-USP1, pCAM-USP2, pCAM-USP3, pCAM-USP4, pCAM-USP5, and pCAM-USP6."
BAP1 affects USP3
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BAP1 binds USP3 and KLF5. 1 / 1
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"Both BAP1 and USP3 bind to and stabilize KLF5 via deubiquitination [ xref , xref ], indicating the possible regulatory role of DUBs in cancer proliferation."
BACH2 affects USP3
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BACH2 decreases the amount of USP3. 1 / 1
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No evidence text available
ATP6V1H affects USP3
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No evidence text available
APH1B affects USP3
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APH1B decreases the amount of USP3. 1 / 1
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"Among SNPs at the locus with P < 1 × 10 , many have been reported as cis-eQTLs in whole blood and other tissues with febrile seizures risk alleles corresponding to decreased expression of HERC1, USP3, DAPK2 and PLEKHO2, and increased expression of FBXL22, APH1B and RBPMS2 (Supplementary Table 5)."
ALYREF affects MYCN, and USP3
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ALYREF binds USP3 and MYCN. 1 / 1
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"The ALYREF-USP3-MYCN complex is a potential therapeutic target for NB by exploiting obligatory ALYREF dependence in MYCN-amplified cells [37]."
AC092894.1 affects USP3
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AC092894.1 binds USP3. 1 / 1
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"This further demonstrated the binding of AC092894.1 to USP3 (Fig. 6G)."
6-propyl-2-thiouracil decreases the amount of USP3. 1 / 1
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No evidence text available

No evidence text available
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17beta-estradiol decreases the amount of USP3. 1 / 1
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No evidence text available
17alpha-ethynylestradiol decreases the amount of USP3. 1 / 1
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No evidence text available
1,2-dimethylhydrazine decreases the amount of USP3. 1 / 1
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No evidence text available