IndraLab
Statements
UCHL3 is modified
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UCHL3 is phosphorylated.
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rlimsp
"Lastly, we provide evidence showing that DNA damage-induced UCHL3 phosphorylation (which is dependent on UCHL3 catalytic activity, ATM kinase and downstream NHEJ factors) promotes destabilization of UCHL3, suggesting that UCHL3 may dissociate from Ku80 to allow Ku ubiquitylation and subsequent removal from DNA."
rlimsp
"Altogether, these data suggest that phosphorylation of UCHL3 on S75, which is dependent on ATM, UCHL3′s catalytic activity and downstream NHEJ factors such as XRCC4 and LigaseIV, regulates Ku80 ubiquitylation by regulating UCHL3 stability rather than affecting its deubiquitylating activity after DSB induction."
rlimsp
"The ensuing results demonstrated that the S75A mutation abolished the signal from the anti-phospho-S/TQ antibody, thus confirming that Ser75 of UCHL3 is phosphorylated in response to DSBs (Supplementary Fig. S6C). We also sought to establish the function of this UCHL3 phosphorylation. In an in vitro deubiquitylating activity assay, purified UCHL3 harbouring either S75A (unphosphorylatable mutant) or S75E (phosphomimetic mutant) showed comparable levels of binding to HA-tagged ubiquitin vinyl sulfone (HA-Ub-VS), which covalently binds to DUB active sites, when compared with wild-type UCHL3, suggesting that Ser75 phosphorylation does not affect the intrinsic enzymatic activity of UCHL3 (Supplementary Fig."
sparser
"Altogether, these data suggest that phosphorylation of UCHL3 on S75, which is dependent on ATM, UCHL3′s catalytic activity and downstream NHEJ factors such as XRCC4 and LigaseIV, regulates Ku80 ubiquitylation by regulating UCHL3 stability rather than affecting its deubiquitylating activity after DSB induction."
rlimsp
"UCHL3 is phosphorylated on S75 in a manner dependent on its catalytic activity, ATM and XRCC4 (as well as LIG4). Although this phosphorylation neither affects the enzymatic activity of UCHL3 in vitro nor its interaction with Ku80 in cells, it facilitates destabilization of UCHL3 after DSB induction."
UCHL3 is methylated.
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1
sparser
"Bag4 is a protein-coding gene that plays a role by interacting with various cell death and growth-related proteins, and regulates their activity by binding to hsp70/hsc70 family proteins ( xref ). syn2b is a member of the synaptotagmin gene family, encoding a neuronal phosphoprotein associated with synaptic vesicle cytoplasmic surfaces ( xref ). map3k4 is also a protein-coding gene, and studies have shown that high methylation of map3k4 kinase and low methylation of uchl3, observed in seawater-released marine sticklebacks, can potentially reduce protein ubiquitination levels and serve as an adaptation to osmotic stress ( xref )."
"<span class="match term0">UCHL3</span>, in turn, deubiquitinates <span class="match term1">RAD51</span> and promotes the binding between <span class="match term1">RAD51</span> and BRCA2."
reach
"Reconstituting wild-type UCHL3 but not catalytically inactive UCHL3 (CA) reversed the increase in RAD51 ubiquitination induced by UCHL3 deficiency (Fig. 2E), suggesting that UCHL3 regulates RAD51 ubiquitination through its Ub protease activity.To determine whether UCHL3 directly deubiquitinates RAD51, we performed an in vitro deubiquitination assay."
"Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. | UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3."
"Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. | UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3."
sparser
"We also performed co-IP experiments to examine the changes in the interaction between RAD51 and UCHL3 in HEK293 cells that were treated with farrerol, and we excluded the possibility that farrerol promoted the deubiquitination of RAD51 by enhancing the UCHL3-RAD51 interaction (Supplementary Fig. xref )."
"Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. | UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3."
"Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. | UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3."
"Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. | UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3."
sparser
"Building on our previous work for computational development of UCH selective UbV-ABPs, we applied a rational design approach to incorporate mutations to the Ub-UCHL3 protein-protein interaction (PPI) interface that would improve binding affinity and impart selectivity over UCHL1 and other DUBs."
sparser
"To do this a binding analysis of the interactions at the PPI interface of both the Ub-UCHL3 (PDB: 1XD3 [ xref ]) and Ub-UCHL1 (PDB: 3KW5 [ xref ]) crystal structure complexes was carried out using BioLuminate (Schrödinger, LLC, New York, NY, USA) in an effort to identify interactions Ub makes that are different between the two DUBs."
reach
"Regulating biological functions, UCHL3 promoted GSC proliferation, tumorigenesis, self-renewal, and radioresistance in a POLD4-dependent manner.The degradation of POLD4 by ubiquitin ligases in response to DNA damage and during cell cycle progression plays a less prominent role in normal cells [43], while with increasing insights into the complex mechanisms of DNA damage repair, POLD4 is projected to play an increasingly important role."
sparser
"Building on our previous work for computational development of UCH selective UbV-ABPs, we applied a rational design approach to incorporate mutations to the Ub-UCHL3 protein-protein interaction (PPI) interface that would improve binding affinity and impart selectivity over UCHL1 and other DUBs."
sparser
"To do this a binding analysis of the interactions at the PPI interface of both the Ub-UCHL3 (PDB: 1XD3 [ xref ]) and Ub-UCHL1 (PDB: 3KW5 [ xref ]) crystal structure complexes was carried out using BioLuminate (Schrödinger, LLC, New York, NY, USA) in an effort to identify interactions Ub makes that are different between the two DUBs."
reach
"In our study, we found that the ubiquitin–proteasome system (UPS) was modulated by the regulation of some ubiquitin enzyme and ligases genes (uchl3, trim 25, trim39, ubr7 and ube2i) and proteasome subunits (psma4, psma6, psmb10, psmc2 and rad23a), which act as protein binding signalling and protein degradation, respectively."
reach
"However, it is possible that β-catenin signaling activated by UCH-L3 is required to maintain the stem cell properties of GCSCs during autophagy-activating conditions, such as nutrient deprivation.In summary, we suppose that the suppression of UCH-L3 could effectively limit gastric cancer recurrence after surgery by preventing GCSC induction."
reach
"However, whether UCHL3 is involved in the deubiquitination of CTNNB1 and its role in bladder cancer remain unknown.The aim of this study is to elucidate the mechanisms underlying the impact of UCHL3 on the initiation and progression of bladder cancer and to identify potential targets for its treatment."
reach
"Therefore, UCHL3 might suppress the ubiquitin-driven degradation of CTNNB1 and thereby trigger the Wnt signaling pathway, resulting in tumorigenic promotion.Although the stabilization of UCHL3 depends on its deubiquitinating activity, UCHL3 directly deubiquitinates CTNNB1, and the sites of CTNNB1 that are deubiquitinated by UCHL3 need to be identified.In summary, we showed that UCHL3 expression is amplified in bladder cancer and functions as a tumor promoter that enhances the proliferation and migration of bladder cancer cells in vitro and to bladder tumorigenesis and tumor progression in vivo."
reach
"Therefore, UCHL3 might suppress the ubiquitin-driven degradation of CTNNB1 and thereby trigger the Wnt signaling pathway, resulting in tumorigenic promotion.Although the stabilization of UCHL3 depends on its deubiquitinating activity, UCHL3 directly deubiquitinates CTNNB1, and the sites of CTNNB1 that are deubiquitinated by UCHL3 need to be identified.In summary, we showed that UCHL3 expression is amplified in bladder cancer and functions as a tumor promoter that enhances the proliferation and migration of bladder cancer cells in vitro and to bladder tumorigenesis and tumor progression in vivo."
reach
"In summary, our experiments indicate that UCHL3 is a specific DUB for AhR and that UCHL3 elevates AhR protein stabilization through deubiquitination.We further detected mRNA levels in 35 paired ADC and SCC lung cancer and corresponding paracancerous normal tissues (Supplementary Fig. S4b, c) and noted no difference between histologic subtypes."
reach
"According to Western blot analysis results, protein levels of UCHL3, AhR and PD-L1 were all reduced in response to sh-UCHL3 treatment, while additional LV-AhR restored the protein levels of AhR and PD-L1 but showed on obvious effects on the UCHL3 protein level; consistently, LV-UCHL3 led to up-regulated protein levels of UCHL3, AhR and PD-L1, among which only the up-regulation of AhR and PD-L1 was reversed in response to additional sh-AhR treatment (Fig. 2M)."
sparser
"Here, we report multiple evidence showing a direct role of UCHL3 in controlling TDP1 proteostasis: (1) reduction of K48-ubiquitylated TDP1 in cancer cells overexpressing UCHL3, (2) reduction of K48-uibiquitylated TDP1 upon addition of recombinant UCHL3, (3) enrichment of K48-ubiquitylated TDP1 upon MG132 treatment, which is dependent on UCHL3 levels, (4) epistatic relationship showing that co-depletion of TDP1 and UCHL3 does not further sensitize cells to TOP1 poisons than depletion of either enzyme alone, (5) physical interaction between TDP1 and UCHL3, and (6) changes in the ubiquitylation status and TDP1 turnover upon changes in UCHL3 levels induced by its ectopic overexpression, siRNA depletion, CRISPR editing, and pharmacologic inhibition and, also, in two physiologically relevant clinical settings."
sparser
"We also performed co-IP experiments to examine the changes in the interaction between RAD51 and UCHL3 in HEK293 cells that were treated with farrerol, and we excluded the possibility that farrerol promoted the deubiquitination of RAD51 by enhancing the UCHL3-RAD51 interaction (Supplementary Fig. xref )."
reach
"Taken together, these data indicated that farrerol promoted DNA repair by HR in a UCHL3-dependent manner.Since the cocrystal structure of the UCHL3–farrerol complex revealed that farrerol directly binds to UCHL3 (Fig. 2a–c), a ubiquitin–AMC assay was then performed to determine whether farrerol activates UCHL3 enzymatic activity, and we found that farrerol affected both K and K , by slightly increasing K from 47.72 to 56.27 nM and significantly increasing K from 11.99 to 19.64 s (Fig. 3i), suggesting that farrerol activates UCHL3 deubiquitinase activity."
reach
"Since we demonstrated that farrerol binds to UCHL3 through two amino acid residues to activate its enzymatic activity, in order to treat HR-overactivated cancer or overcome radio/chemo-resistance, it is likely worthwhile to try generating farrerol derivatives that exhibit an inhibitory effect on UCHL3 while still retaining a high affinity to UCHL3.It was reported that genomic stability is critical in the dynamic process of somatic cells reprogramming into iPSCs and is essential for the pluripotency of ESCs and iPSCs, whereas chromosomal aneuploidy results in a sharp decrease in cell differentiation potentials in vivo ."
reach
"Further thorough studies on whether farrerol directly targets these proteins and the underlying mechanisms might open up new avenues for the application of farrerol when treating other types of diseases.Notably, several reports also indicated that UCHL3 is aberrantly overexpressed in different types of tumors, so caution should be taken when utilizing farrerol, as the farrerol-mediated activation of UCHL3 might be dangerous for cancer patients."
reach
"Taken together, these data indicated that farrerol promoted DNA repair by HR in a UCHL3-dependent manner.Since the cocrystal structure of the UCHL3–farrerol complex revealed that farrerol directly binds to UCHL3 (Fig. 2a–c), a ubiquitin–AMC assay was then performed to determine whether farrerol activates UCHL3 enzymatic activity, and we found that farrerol affected both K and K , by slightly increasing K from 47.72 to 56.27 nM and significantly increasing K from 11.99 to 19.64 s (Fig. 3i), suggesting that farrerol activates UCHL3 deubiquitinase activity."
reach
"Our data demonstrated the tumor-promoting function of UCHL3 in bladder cancer, suggesting that targeting UCHL3 might be a potential approach for preventing bladder tumorigenesis and progression.Previously, UCHL3 has been found to be robustly expressed in epithelial ovarian cancer and related to intra-abdominal metastases [29]."
reach
"RT-qPCR analysis demonstrated no significant differences in UCHL3, NEDD8 and LC3B expression levels between the NC and si-NC groups (P>0.05; Fig. 4A and B); however, UCHL3 knockdown significantly decreased the expression levels of UCHL3 and NEDD8, and significantly increased LC3B expression in the si-UCHL3 group compared with the NC group (all P<0.001; Fig. 4A and B)."
UCHL3 affects cell population proliferation
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UCHL3 activates cell population proliferation.
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UCHL3 activates cell population proliferation. 10 / 13
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"Regulating biological functions, UCHL3 promoted GSC proliferation, tumorigenesis, self-renewal, and radioresistance in a POLD4-dependent manner.The degradation of POLD4 by ubiquitin ligases in response to DNA damage and during cell cycle progression plays a less prominent role in normal cells [43], while with increasing insights into the complex mechanisms of DNA damage repair, POLD4 is projected to play an increasingly important role."
reach
"Furthermore, autophagy was significantly enhanced along with the decrease in NEDD8 ubiquitination.In conclusion, the results of the present study demonstrated that UCHL3 knockdown decreased melanoma cell proliferation by increasing cell autophagy through regulating NEDD8 expression and autophagosome numbers in vitro."
UCHL3 inhibits cell population proliferation.
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UCHL3 inhibits cell population proliferation. 2 / 2
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sparser
"Here, we report multiple evidence showing a direct role of UCHL3 in controlling TDP1 proteostasis: (1) reduction of K48-ubiquitylated TDP1 in cancer cells overexpressing UCHL3, (2) reduction of K48-uibiquitylated TDP1 upon addition of recombinant UCHL3, (3) enrichment of K48-ubiquitylated TDP1 upon MG132 treatment, which is dependent on UCHL3 levels, (4) epistatic relationship showing that co-depletion of TDP1 and UCHL3 does not further sensitize cells to TOP1 poisons than depletion of either enzyme alone, (5) physical interaction between TDP1 and UCHL3, and (6) changes in the ubiquitylation status and TDP1 turnover upon changes in UCHL3 levels induced by its ectopic overexpression, siRNA depletion, CRISPR editing, and pharmacologic inhibition and, also, in two physiologically relevant clinical settings."
UCHL3 affects Neoplasm Metastasis
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UCHL3 activates Neoplasm Metastasis.
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UCHL3 inhibits Neoplasm Metastasis.
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UCHL3 inhibits Neoplasm Metastasis. 1 / 2
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UCHL3 inhibits epithelial to mesenchymal transition.
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UCHL3 activates epithelial to mesenchymal transition.
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UCHL3 activates epithelial to mesenchymal transition. 2 / 2
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"Ubiquitin C-terminal hydrolase L3 (UCHL3) as a deubiquitinating enzyme is able to inhibit FOXM1 ubiquitination and degradation 270, while Human leukocyte antigen F-associated transcript 10 (FAT10) as a ubiquitin like protein is able to inhibit FOXM1 ubiquitination and stabilize FOXM1 expression by competing with ubiquitin for binding to FOXM1 271."
UCHL3 affects cell migration
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UCHL3 activates cell migration.
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UCHL3 inhibits cell migration.
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UCHL3 affects Neoplasm Invasiveness
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UCHL3 activates Neoplasm Invasiveness.
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UCHL3 inhibits Neoplasm Invasiveness.
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reach
"Taken together, these data indicated that farrerol promoted DNA repair by HR in a UCHL3-dependent manner.Since the cocrystal structure of the UCHL3–farrerol complex revealed that farrerol directly binds to UCHL3 (Fig. 2a–c), a ubiquitin–AMC assay was then performed to determine whether farrerol activates UCHL3 enzymatic activity, and we found that farrerol affected both K and K , by slightly increasing K from 47.72 to 56.27 nM and significantly increasing K from 11.99 to 19.64 s (Fig. 3i), suggesting that farrerol activates UCHL3 deubiquitinase activity."
reach
"Since we demonstrated that farrerol binds to UCHL3 through two amino acid residues to activate its enzymatic activity, in order to treat HR-overactivated cancer or overcome radio/chemo-resistance, it is likely worthwhile to try generating farrerol derivatives that exhibit an inhibitory effect on UCHL3 while still retaining a high affinity to UCHL3.It was reported that genomic stability is critical in the dynamic process of somatic cells reprogramming into iPSCs and is essential for the pluripotency of ESCs and iPSCs, whereas chromosomal aneuploidy results in a sharp decrease in cell differentiation potentials in vivo ."
reach
"UCHL1 and UCHL3 are 73% similar but display different patterns of tissue specific gene expression : an upstream neuron-restrictive silencing element (NRSE) drives neuron specific expression in the former and renders it a critical player in neuronal homeostasis (UCHL1 deficiency in neurodegeneration is not physiologically rescued by UCHL3)."
reach
"Functional rescue experiments indicated the dependence of UCHL3-mediated HCC cell migration on Vimentin regulation.Previous reports have indicated the deubiquitinating and protein-stabilizing effect of UCHL3 in several human cancer types (19, 20, 22) and demonstrated its contribution to carcinogenesis (14)."
Valproic acid affects UCHL3
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LINC00665 affects UCHL3
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LINC00665 increases the amount of UCHL3.
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5
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"Meanwhile, Western blot analysis unraveled that LINC00665 overexpression alone led to up-regulated protein levels of UCHL3, AhR and PD-L1 in tumor tissues from irradiation-treated tumor-bearing mice, and its combination with AhR silencing led to relatively decreased protein levels of AhR and PD-L1 and almost unchanged UCHL3 expression (Fig. 7D)."
LINC00665 activates UCHL3.
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UCHL3 affects IFN-I
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UCHL3 affects osteoblast differentiation
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UCHL3 affects ossification
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UCHL3 affects cell differentiation
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UCHL3 affects Radiation, Ionizing
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UCHL3 inhibits Radiation, Ionizing.
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UCHL3 inhibits Radiation, Ionizing. 3 / 3
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"To exclude the possibility that the increased IR sensitivity caused by UCHL3 depletion was due to decreased proliferation or cell cycle issues, cell proliferation and cell cycle profile of these cell lines were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based assay and bromodeoxyuridine (BrdU) incorporation assay, respectively (Supplementary Fig. S2A,B)."
UCHL3 activates Radiation, Ionizing.
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UCHL3 affects Carcinogenesis
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UCHL3 activates Carcinogenesis.
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UCHL3 activates Carcinogenesis. 5 / 5
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reach
"Regulating biological functions, UCHL3 promoted GSC proliferation, tumorigenesis, self-renewal, and radioresistance in a POLD4-dependent manner.The degradation of POLD4 by ubiquitin ligases in response to DNA damage and during cell cycle progression plays a less prominent role in normal cells [43], while with increasing insights into the complex mechanisms of DNA damage repair, POLD4 is projected to play an increasingly important role."
UCHL3 inhibits Carcinogenesis.
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UCHL3 inhibits Carcinogenesis. 1 / 1
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reach
"Of note, our experiments were performed in the presence of IL6/8. whether other deubiquitinases are preferential in other contexts need to be further investigated.To investigate if UCHL3 binds to BRD4, we performed reciprocal co-immunoprecipitation assays in cells transfected with BRD4, alone or with UCHL3 and JAK2-V617F."
UCHL3 affects homologous recombination
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UCHL3 inhibits homologous recombination.
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UCHL3 inhibits homologous recombination. 3 / 3
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reach
"Furthermore, UCHL3 was recently suggested to facilitate HR by deubiquitylating RAD51 in a DSB-dependent manner via phosphorylation on the same site that we identified (S75) , however, we did not observe any defects in HR caused by UCHL3 depletion, nor did we detect any interaction with RAD51 in our mass spectrometry analyses."
UCHL3 activates homologous recombination.
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UCHL3 activates homologous recombination. 2 / 2
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UCHL3 affects cell growth
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UCHL3 activates cell growth.
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UCHL3 inhibits cell growth.
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Mutated UCHL3 inhibits cell growth. 1 / 1
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UCHL3 affects Wnt signaling pathway
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UCHL3 activates Wnt signaling pathway.
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UCHL3 inhibits Wnt signaling pathway.
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UCHL3 inhibits Wnt signaling pathway. 1 / 1
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"Western blot analysis showed that the protein levels of Wnt/β-Catenin downstream gene-encoded products were reduced in UCHL3-deficient tumor tissues, including LEF1, Axin2, C-myc and Cyclin D1, confirming that the abolition of UCHL3 inhibited WNT signaling pathway activation, which is consistent with our aforementioned experiments."
UCHL3 increases the amount of UCHL3.
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3
reach
"RT-qPCR analysis demonstrated no significant differences in UCHL3, NEDD8 and LC3B expression levels between the NC and si-NC groups (P>0.05; Fig. 4A and B); however, UCHL3 knockdown significantly decreased the expression levels of UCHL3 and NEDD8, and significantly increased LC3B expression in the si-UCHL3 group compared with the NC group (all P<0.001; Fig. 4A and B)."
reach
"According to Western blot analysis results, protein levels of UCHL3, AhR and PD-L1 were all reduced in response to sh-UCHL3 treatment, while additional LV-AhR restored the protein levels of AhR and PD-L1 but showed on obvious effects on the UCHL3 protein level; consistently, LV-UCHL3 led to up-regulated protein levels of UCHL3, AhR and PD-L1, among which only the up-regulation of AhR and PD-L1 was reversed in response to additional sh-AhR treatment (Fig. 2M)."
UCHL3 activates UCHL3.
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"However, HOTAIR was also reported to reduce the ubiquitination degradation of AR by preventing its combination with MDM2, and GIAT4RA was recently reported to interfere the interaction between Uchl3 and LSH to repress ubiquitin-proteasome pathway [30], which indicate multiple roles of lncRNA in ubiquitination."
UCHL3 affects K27
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"To explore the cleavage preference of UCHL3 for different types of ubiquitin chains and whether phosphorylation modification gives UCHL3 the ability to cleave ubiquitin chains in vitro, different linkages (K6, K11, K27, K48, and K63) of di-Ub were synthesized and tested for their activity of UCHL3 and UCHL3 ."
K27 affects UCHL3
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UCHL3 affects response to xenobiotic stimulus
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UCHL3 activates response to xenobiotic stimulus. 4 / 4
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reach
"However, the effects of the UCHL3/EEF1A1 axis on HCC tumors as revealed by patient-derived xenograft (PDX) models remains to be explored.Therefore, UCHL3 and EEF1A1 jointly promote the migration, stemness, and drug resistance of HCC cells, as well as influencing the growth of mouse tumor models."
sparser
"In the present study, Sp-UCHL3 mRNA expression in T3 was significantly higher than in the T1 and T2 stages ( p < 0.05), while Sp-UCHL5 mRNA expressions in the three stages of testes development were not significantly different from each other ( p > 0.05), indicating that Sp- UCHL3 and Sp- UCHL5 have different aspects in regulating mechanism of testis development."
UCHL3 affects Proteasome
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UCHL3 increases the amount of Proteasome.
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UCHL3-C95S increases the amount of Proteasome. 1 / 1
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"To address whether UCHL3 C95S impedes Ub(G76V)‐GFP turnover at the level of p97 or the proteasome, we employed a variant Ub(G76V)‐GFP protein containing a C‐terminal 20‐amino acid extension (Ub(G76V)‐GFP‐20AA), which has been shown to override the requirement for p97‐mediated unfolding to enable its proteasomal degradation (Beskow et al, 2009; Godderz et al, 2015) (Fig 5E)."
UCHL3 increases the amount of Proteasome. 1 / 1
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UCHL3 inhibits Proteasome.
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UCHL3 inhibits Proteasome. 1 / 1
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UCHL3 activates Proteasome.
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UCHL3 activates Proteasome. 1 / 1
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"In our study, we found that the ubiquitin–proteasome system (UPS) was modulated by the regulation of some ubiquitin enzyme and ligases genes (uchl3, trim 25, trim39, ubr7 and ube2i) and proteasome subunits (psma4, psma6, psmb10, psmc2 and rad23a), which act as protein binding signalling and protein degradation, respectively."
UCHL3 affects Ku80 chromatin binding
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4
reach
"According to Western blot analysis results, protein levels of UCHL3, AhR and PD-L1 were all reduced in response to sh-UCHL3 treatment, while additional LV-AhR restored the protein levels of AhR and PD-L1 but showed on obvious effects on the UCHL3 protein level; consistently, LV-UCHL3 led to up-regulated protein levels of UCHL3, AhR and PD-L1, among which only the up-regulation of AhR and PD-L1 was reversed in response to additional sh-AhR treatment (Fig. 2M)."
sparser
"In the present study, Sp-UCHL3 mRNA expression in T3 was significantly higher than in the T1 and T2 stages ( p < 0.05), while Sp-UCHL5 mRNA expressions in the three stages of testes development were not significantly different from each other ( p > 0.05), indicating that Sp- UCHL3 and Sp- UCHL5 have different aspects in regulating mechanism of testis development."
RA-9 affects UCHL3
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4
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"Of note, our experiments were performed in the presence of IL6/8. whether other deubiquitinases are preferential in other contexts need to be further investigated.To investigate if UCHL3 binds to BRD4, we performed reciprocal co-immunoprecipitation assays in cells transfected with BRD4, alone or with UCHL3 and JAK2-V617F."
4,4'-sulfonyldiphenol affects UCHL3
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4,4'-sulfonyldiphenol increases the amount of UCHL3.
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4,4'-sulfonyldiphenol decreases the amount of UCHL3.
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Trichostatin A affects UCHL3
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Sodium arsenite affects UCHL3
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Cobalt dichloride affects UCHL3
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UCHL3 binds.
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UCHL3 is active.
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UCHL3 affects glioblastoma multiforme cancer stem cell
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"Regulating biological functions, UCHL3 promoted GSC proliferation, tumorigenesis, self-renewal, and radioresistance in a POLD4-dependent manner.The degradation of POLD4 by ubiquitin ligases in response to DNA damage and during cell cycle progression plays a less prominent role in normal cells [43], while with increasing insights into the complex mechanisms of DNA damage repair, POLD4 is projected to play an increasingly important role."
UCHL3 affects apoptotic process
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3
reach
"Overexpression of UCH-L1, but not of UCH-L3 (the other human homolog of UBH1) or of the catalytic mutant UCH L1C90A, enhanced TGF-beta and SMAD-induced transcriptional activity, indicating that the deubiquitination activity of UCH-L1 is indispensable for enhancing TGF-beta and SMAD signaling."
reach
"Overexpression of UCH-L1, but not of UCH-L3 (the other human homolog of UBH1) or of the catalytic mutant UCH-L1 C90A, enhanced TGF-beta and SMAD-induced transcriptional activity, indicating that the deubiquitination activity of UCH-L1 is indispensable for enhancing TGF-beta and SMAD signaling."
UCHL3 affects OTULIN ABP
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"Lastly, we provide evidence showing that DNA damage-induced UCHL3 phosphorylation (which is dependent on UCHL3 catalytic activity, ATM kinase and downstream NHEJ factors) promotes destabilization of UCHL3, suggesting that UCHL3 may dissociate from Ku80 to allow Ku ubiquitylation and subsequent removal from DNA."
OTULIN ABP affects UCHL3
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Delta12-PGJ2 affects UCHL3
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Δ affects UCHL3
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Titanium dioxide affects UCHL3
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Titanium dioxide increases the amount of UCHL3.
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Titanium dioxide demethylates UCHL3.
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Sodium citrate dihydrate affects UCHL3
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Pirinixic acid affects UCHL3
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Phenylmercury acetate affects UCHL3
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reach
"The largest stabilization was seen upon the addition of peptide 60297, which increased the melting temperature of PfUCHL3 by 5.1 °C, followed by peptide 60296 which increased the melting temperature by 3.1 °C at 25 μM. Peptides 58474 and 58474(2) were the only other two peptides to cause a significant increase in the melting temperature (1.2 °C and 1.3 °C, respectively)."
Paracetamol affects UCHL3
2
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Lysozyme activity affects UCHL3
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2
Lysine affects UCHL3
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2
Lsh affects UCHL3
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2
sparser
"However, HOTAIR was also reported to reduce the ubiquitination degradation of AR by preventing its combination with MDM2, and GIAT4RA was recently reported to interfere the interaction between Uchl3 and LSH to repress ubiquitin-proteasome pathway [ xref ], which indicate multiple roles of lncRNA in ubiquitination."
Hsa-mir-3941 affects UCHL3
2
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Hsa-miR-875-5p affects UCHL3
2
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Hsa-miR-8485 affects UCHL3
2
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Hsa-miR-5580-3p affects UCHL3
2
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Hsa-miR-5011-5p affects UCHL3
2
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Hsa-miR-4789-3p affects UCHL3
2
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Hsa-miR-362-3p affects UCHL3
2
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Hsa-miR-329-3p affects UCHL3
2
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Hsa-miR-3144-3p affects UCHL3
2
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Hsa-miR-190a-3p affects UCHL3
2
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Cyclosporin A affects UCHL3
2
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Cyclic peptide affects UCHL3
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2
Cyclic peptide inhibits UCHL3. 1 / 1
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1
reach
"These points highlight the ubiquitin pathway as a promising target for the development of novel antimalarials.In this study, we used the RaPID selection technique to identify cyclic peptide inhibitors of PfUCHL3, a dual activity DUB/deneddylating enzyme of P. falciparum, the deadliest malaria parasite."
Cyclic peptide inhibits UCHL3. 1 / 1
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1
Bisphenol A affects UCHL3
2
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UCHL3 affects regulation of cell cycle
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2
UCHL3 activates regulation of cell cycle. 2 / 2
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2
UCHL3 affects lysozyme activity
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2
UCHL3 affects lysine
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2
UCHL3 affects lsh
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2
sparser
"However, HOTAIR was also reported to reduce the ubiquitination degradation of AR by preventing its combination with MDM2, and GIAT4RA was recently reported to interfere the interaction between Uchl3 and LSH to repress ubiquitin-proteasome pathway [ xref ], which indicate multiple roles of lncRNA in ubiquitination."
UCHL3 affects inflammatory response
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1
1
UCHL3 affects glycolytic process
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2
UCHL3 activates glycolytic process. 2 / 2
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2
UCHL3 affects ferroptosis
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2
UCHL3 inhibits ferroptosis. 2 / 2
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2
UCHL3 affects fat cell differentiation
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2
UCHL3 affects cell death
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2
reach
"Furthermore, autophagy was significantly enhanced along with the decrease in NEDD8 ubiquitination.In conclusion, the results of the present study demonstrated that UCHL3 knockdown decreased melanoma cell proliferation by increasing cell autophagy through regulating NEDD8 expression and autophagosome numbers in vitro."
UCHL3 affects Thyroid Carcinoma, Anaplastic
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2
UCHL3 affects Recurrence
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2
UCHL3 affects Neoplastic Stem Cells
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2
reach
"Furthermore, autophagy was significantly enhanced along with the decrease in NEDD8 ubiquitination.In conclusion, the results of the present study demonstrated that UCHL3 knockdown decreased melanoma cell proliferation by increasing cell autophagy through regulating NEDD8 expression and autophagosome numbers in vitro."
UCHL3 affects DNA repair
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2
UCHL3 activates DNA repair. 2 / 2
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2
UCHL3 affects DNA Damage
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2
UCHL3 activates DNA Damage. 2 / 2
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2
reach
"Regulating biological functions, UCHL3 promoted GSC proliferation, tumorigenesis, self-renewal, and radioresistance in a POLD4-dependent manner.The degradation of POLD4 by ubiquitin ligases in response to DNA damage and during cell cycle progression plays a less prominent role in normal cells [43], while with increasing insights into the complex mechanisms of DNA damage repair, POLD4 is projected to play an increasingly important role."
UCHL3 affects Cell Survival
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1
1
UCHL3 activates Cell Survival. 2 / 2
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1
1
eidos
"UCHL3 promotes cell survival after DSB induction and is epistatic with XRCC4 To further explore whether UCHL3 plays a role in cellular responses to DSBs , clonogenic survival assays were performed upon treating cells with various short interfering RNAs ( siRNAs ) targeting UCHL3 ."
UCHL3 affects Carcinoma, Hepatocellular
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2
UCHL3 affects CRY2 methylation
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2
TCID affects UCHL3
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2
reach
"However, HOTAIR was also reported to reduce the ubiquitination degradation of AR by preventing its combination with MDM2, and GIAT4RA was recently reported to interfere the interaction between Uchl3 and LSH to repress ubiquitin-proteasome pathway [30], which indicate multiple roles of lncRNA in ubiquitination."
Gentamicins affects UCHL3
2
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Gentamicins increases the amount of UCHL3.
1
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Gentamicins decreases the amount of UCHL3.
1
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EEF1A1 affects lysine
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2
AM146 affects UCHL3
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2
Trimellitic anhydride affects UCHL3
1
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Trifluoperazine affects UCHL3
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1
Trifluoperazine inhibits UCHL3. 1 / 1
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1
Trichloroethene affects UCHL3
1
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Sodium chloride affects UCHL3
1
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Silicon dioxide affects UCHL3
1
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Reported Akt affects UCHL3
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1
Polyubiquitin affects UCHL3
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1
Phosphorylation affects UCHL3
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1
Phosphorylation inhibits UCHL3. 1 / 1
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1
Phorbol 13-acetate 12-myristate affects UCHL3
1
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Perifosine affects UCHL3
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1
Perifosine inhibits UCHL3. 1 / 1
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1
Perfluorooctane-1-sulfonic acid affects UCHL3
1
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MiR-582-5p affects UCHL3
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1
Methylmercury chloride affects UCHL3
1
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Methapyrilene affects UCHL3
1
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Lead(II) chloride affects UCHL3
1
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Ivermectin affects UCHL3
1
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Hsa-mir-4534 affects UCHL3
1
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Hsa-mir-3134 affects UCHL3
1
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Hsa-miR-8082 affects UCHL3
1
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Hsa-miR-7156-5p affects UCHL3
1
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Hsa-miR-532-5p affects UCHL3
1
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Hsa-miR-514b-5p affects UCHL3
1
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Hsa-miR-5093 affects UCHL3
1
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Hsa-miR-4633-5p affects UCHL3
1
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Hsa-miR-372-5p affects UCHL3
1
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Hsa-miR-3688-3p affects UCHL3
1
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Hsa-miR-3124-3p affects UCHL3
1
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Hsa-miR-130b-5p affects UCHL3
1
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Hexabromocyclododecane affects UCHL3
1
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reach
"These results demonstrate that extended gefitinib exposure induces sustained UCHL3 downregulation and USP54 upregulation in gefitinib-resistant sublines, suggesting a potential interplay between these genes in NSCLC cells under prolonged drug exposure.Total RNA was extracted from PC9 cells treated with 1 μM gefitinib for 1, 6, and 24 h and analyzed by QuantSeq 3’ mRNA sequencing."
Folic acid affects UCHL3
1
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Electrophilic reagent affects UCHL3
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1
Electrophilic reagent inhibits UCHL3. 1 / 1
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sparser
"These endogenous electrophiles (1) inhibit ubiquitin isopeptidase activity [ xref ] as well as ubiquitin hydrolases UCH-L1 and UCH-L3 [ xref ], (2) induce the formation of cysteine-targeted thyolation of UCH-L1 [ xref ] and of PGJ2/proteasome conjugates [ xref ], (3) trigger the oxidation of the S6 ATPase subunit of the 26S proteasome [ xref ], and disrupt 26S proteasome assembly [ xref ]."
1
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Dibutyl phthalate affects UCHL3
1
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Dibenzothiophene affects UCHL3
1
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Deltamethrin affects UCHL3
1
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Cyanoginosin LR affects UCHL3
1
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Cannabidiol affects UCHL3
1
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Bisphenol F affects UCHL3
1
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Bisphenol B affects UCHL3
1
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Bis(2-ethylhexyl) phthalate affects UCHL3
1
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Beta-lapachone affects UCHL3
1
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Beta-D-glucose affects UCHL3
1
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Benzatropine affects UCHL3
1
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Arsenite(3-) affects UCHL3
1
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sparser
"We found complex viscosity dependencies and interpreted these in the context of a model in which association and acylation are viscosity-dependent but deacylation is viscosity-independent. (2) The kinetics of inhibition of UCH-L3 by ubiquitin C-terminal aldehyde (Ub-H) were determined and reveal a Ki that is less than 10(-14) M. Several mechanisms are considered to account for the extreme inhibition. (3) The IPaseT-catalyzed hydrolysis of Ub-AMC is modulated by Ub with activation at low [Ub] and inhibition at high [Ub]. (4) Finally, we compare kc/Km values for deubiquitinating enzyme-catalyzed hydrolysis of Ub-AMC and Z-Leu-Arg-Gly-Gly-AMC."
Acetaldehyde affects UCHL3
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1
Acetaldehyde binds UCHL3. 1 / 1
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1
VEA-260 affects UCHL3
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1
UbVME affects UCHL3
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1
Ub dimers affects UCHL3
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1
USP2cd affects UCHL3
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1
UCHL3 affects ubiquitination TDP1 leading TDP1
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1
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1
UCHL3 inhibits ubiquitin carboxyl-terminal hydrolase. 1 / 1
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1
UCHL3 affects subsequent removal DNA
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1
eidos
"Lastly , we provide evidence showing that DNA damage-induced UCHL3 phosphorylation ( which is dependent on UCHL3 catalytic activity , ATM kinase and downstream NHEJ factors ) promotes destabilization of UCHL3 , suggesting that UCHL3 may dissociate from Ku80 to allow Ku ubiquitylation and subsequent removal from DNA ."
UCHL3 affects repair
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1
UCHL3 affects radiosensitivity NSCLC cells
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1
UCHL3 affects proteolysis
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1
UCHL3 activates proteolysis. 1 / 1
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1
UCHL3 affects protein ubiquitination
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1
UCHL3 inhibits protein ubiquitination. 1 / 1
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1
reach
"map3k4 is also a protein-coding gene, and studies have shown that high methylation of map3k4 kinase and low methylation of uchl3, observed in seawater-released marine sticklebacks, can potentially reduce protein ubiquitination levels and serve as an adaptation to osmotic stress (Artemov et al., 2017)."
UCHL3 affects polyubiquitin
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1
UCHL3 affects polyubiquitin chains
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1
UCHL3 affects polyubiquitin chain
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1
UCHL3 affects pY701-STAT1
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1
UCHL3 affects monoubiquitin
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1
reach
"Recent evidence suggests that monoubiquitin release from its precursors is mediated predominantly by five main DUBs : ubiquitin thioesterase otulin, UCHL3, USP5, USP7 and USP9X [XREF_BIBR], although each has multiple substrates that can be targeted for deubiquitination to maintain the free ubiquitin pool."
UCHL3 affects mono-Ub
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1
UCHL3 affects mineralization
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1
UCHL3 inhibits mineralization. 1 / 1
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1
UCHL3 affects migration
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1
UCHL3 affects localization
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1
UCHL3 activates localization. 1 / 1
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1
UCHL3 affects localization Aurora B kinetochores
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1
UCHL3 affects embryo development
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1
UCHL3 inhibits embryo development. 1 / 1
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1
UCHL3 affects differentiation osteoblast C2C12 cells
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1
UCHL3 affects cleave
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1
UCHL3 affects chromosome alignment defects
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1
UCHL3 affects chromatin retention
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1
UCHL3 affects cell division
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1
UCHL3 inhibits cell division. 1 / 1
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1
UCHL3 affects acetaldehyde
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1
Acetaldehyde binds UCHL3. 1 / 1
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1
UCHL3 affects VSV-G
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1
UCHL3 affects UbVME
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1
UCHL3 affects UCHL3 KO
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1
UCHL3 affects UCH Yuh1
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1
"Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors."
UCHL3 affects Smad1.To
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1
UCHL3 affects Rho-Ub-PA
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1
reach
"The activity of UCHL3 was also monitored using the fluorescent Ub-propargylamide (PA) DUB ABP Rho-Ub-PA.3 d Fluorescent bands corresponding to UCHL3 bound to Rho-Ub-PA were observed for both unlabeled UCHL3 and DTT treated Ub SS -UCHL3 complexes, but not for untreated Ub SS -UCHL3 complexes."
UCHL3 affects LC3II
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1
UCHL3 affects LC3B
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1
reach
"RT-qPCR analysis demonstrated no significant differences in UCHL3, NEDD8 and LC3B expression levels between the NC and si-NC groups (P>0.05; Fig. 4A and B); however, UCHL3 knockdown significantly decreased the expression levels of UCHL3 and NEDD8, and significantly increased LC3B expression in the si-UCHL3 group compared with the NC group (all P<0.001; Fig. 4A and B)."
UCHL3 affects Ku ubiquitylation
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1
eidos
"Lastly , we provide evidence showing that DNA damage-induced UCHL3 phosphorylation ( which is dependent on UCHL3 catalytic activity , ATM kinase and downstream NHEJ factors ) promotes destabilization of UCHL3 , suggesting that UCHL3 may dissociate from Ku80 to allow Ku ubiquitylation and subsequent removal from DNA ."
UCHL3 affects K469
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1
UCHL3 affects Interferon
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1
UCHL3 activates Interferon. 1 / 1
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1
UCHL3 affects IFN-I receptors
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1
UCHL3 affects GFP-β-catenin
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1
UCHL3 affects G0/G1
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1
UCHL3 affects Fig. 3F-I
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1
UCHL3 affects Deubiquitinase
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1
UCHL3 activates Deubiquitinase. 1 / 1
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1
UCHL3 inhibitors affects UCHL3
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1
UCH Yuh1 affects UCHL3
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1
Senkirkine affects UCHL3
1
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Rho-Ub-PA affects UCHL3
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1
reach
"The activity of UCHL3 was also monitored using the fluorescent Ub-propargylamide (PA) DUB ABP Rho-Ub-PA.3 d Fluorescent bands corresponding to UCHL3 bound to Rho-Ub-PA were observed for both unlabeled UCHL3 and DTT treated Ub SS -UCHL3 complexes, but not for untreated Ub SS -UCHL3 complexes."
Radiation, Ionizing affects UCHL3
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1
Radiation, Ionizing leads to the phosphorylation of UCHL3. 1 / 1
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1
Proteasome affects UCHL3
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1
Proteasome activates UCHL3. 1 / 1
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1
reach
"In addition, several ubiquitin-proteasome-related proteins (ubiquitin-activating enzyme E1, ubiquitin C-terminal hydrolase UCHL3 and proteasome 26S regulatory subunit) were crotonylated and 2-hydroxyisobutyrylated in the phenotypically different T. gondii parasites (supplemental Data S21)."
PR-619 affects UCHL3
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1
MMV676603 affects UCHL3
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1
LDN57444 affects UCHL3
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1
LDN-57444 affects UCHL3
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1
LDN affects UCHL3
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1
K469 affects UCHL3
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1
Infections affects UCHL3
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1
Infections activates UCHL3. 1 / 1
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1
GFP-β-catenin affects UCHL3
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1
Environmental Pollutants affects UCHL3
1
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DNA UCHL3 phosphorylation affects UCHL3
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1
eidos
"Lastly , we provide evidence showing that DNA damage-induced UCHL3 phosphorylation ( which is dependent on UCHL3 catalytic activity , ATM kinase and downstream NHEJ factors ) promotes destabilization of UCHL3 , suggesting that UCHL3 may dissociate from Ku80 to allow Ku ubiquitylation and subsequent removal from DNA ."
2-hydroxypropanoic acid affects UCHL3
1
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2,6-dimethoxyphenol affects UCHL3
1
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1
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1H-pyrazole affects UCHL3
1
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15Delta-PGJ2 affects UCHL3
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1
1,2-dichloroethane affects UCHL3
1
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