IndraLab
Statements
UCHL1 is modified
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UCHL1 is methylated.
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139
UCHL1 is farnesylated.
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40
sparser
"It is tempting to speculate that UCH-L1 plays different roles in these two distinct processes of ECV formation and that, as a deubiquitinating enzyme, UCH-L1 is an active participant in the development of multivesicular bodies (MVBs), while farnesylation of UCH-L1 is required for the loading of exosomal cargo."
sparser
"Considering that the fractions of the exosomes reported in xref and those of the ectosomes reported in xref were taken from the same experiment, we concluded that UCH-L1 C-terminal farnesylation at cysteine 220 (as well as cellular farnesylation inhibited by FTI-277) regulates LMP1 targeting explicitly to exosomes."
UCHL1 is ubiquitinated.
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13
sparser
"Our TUBE analysis of endogenous UCH-L1 ubiquitination in mouse brain revealed the presence of multiple polyubiquitinated UCH-L1 forms as well as a ~40 kDa diubiquitinated UCH-L1 species (which could also represent UCH-L1 monoubiquitination at two sites), but no ~33 kDa monoubiquitinated UCH-L1 species."
sparser
"Tissue lysates were immunoprecipitated by ubiquitin, HSPA2, and UCHL1 antibodies and the control (immunoglobulin G [IgG]), the ubiquitinated proteins HSPA2 and UCHL1 were presented in the ubiquitin‐IP pulldown and the protein ubiquitin was presented in the UCHL1‐IP and HSPA2‐IP pulldown as well, compared with IgG control by Western blot analysis."
UCHL1 is phosphorylated.
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9
sparser
"Cell lysates prepared 72 h post transfection for western blotting studies revealed reduced levels of UCHL1 and AktS473 phosphorylation, quantified by densitometric analysis (*p < 0.05 control vs. UCHL1 siRNA). (D) UCHL1 protein expression was assessed in lung homogenates obtained from LPS/VILI-exposed Yucatan minipigs (n = 3) with and without treatment with the eNAMPT-neutralizing mAb. lung homogenates (n = 3) compared to control pig tissues."
UCHL1 is produced.
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sparser
"Initially, the most Figure 7 An overlay of X-ray structures of apo UCHL1 (2ETL, yellow (light grey in the print version)) and UCHL1 bound to ubiquitin VME (3KW5, enzyme is purple (dark grey in the print version) and ubiquitin VME is green (grey in the print version)).
commonly used substrate was ubiquitin coupled via its carboxy-terminus onto the amino group of the fluorescent tag 7-amino-4-methylcoumarin (Ub-AMC)."
sparser
"Analog 34 inhibited HA-Ub-VME complex formation with UCHL1 in a dose-dependent manner ( xref B, top panel) and demonstrated selectivity over other DUBs in SW1271 cells as the only band in the HA-blot to exhibit significant dose-dependent signal reduction was the Ub-UCHL1 band ( xref B, bottom panel)."
sparser
"In contrast, the impacts of ubiquitin binding to UCH-L1 and -L3 are mostly limited to the conformational rearrangements in the cross-over loops and flanking regions, and, in the case of UCH-L1, a cascade of side-chain movements to align catalytic residues into a productive configuration xref xref ."
reach
"The I93M mutation in the UCH-L1 gene, which was reported in a German family with autosomal dominant Parkinson 's Disease (PD), leads to a 50% reduction in catalytic of UCH-L1 activity in vitro, implying that loss of UCH-L1 activity may reduce the availability of free ubiquitin, and contribute to an impaired clearance of proteins by the UPS."
reach
"In addition, western blotting of proteins from primary cells derived from the spinal ligament tissues of wild-type mice treated with the ubiquitin ligase inhibitor (HLI 373), treated with recombinant UCHL1, or transfected with miR-340 showed that expression of CXCL7 was not completely suppressed by miR-340 transfection."
UCHL1 affects cell population proliferation
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3
UCHL1 activates cell population proliferation.
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UCHL1 inhibits cell population proliferation.
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UCHL1 inhibits cell population proliferation. 10 / 40
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"In the present study, there are several novel findings regarding UCH-L1 as a negative regulator of maladaptive cardiac remodeling and dysfunction as follows : (i) UCH-L1 expression is enhanced in cardiac myocytes and fibroblasts during the earlier stage of cardiac adaptive hypertrophy and declined in the process of maladaptive responses to the sustained hemodynamic stress; (ii) UCH-L1 inhibits cardiac fibroblast proliferation via suppressing PDGF and PDGFRbeta signaling; (iii) UCH-L1 preferentially enhances PDGF-BB-induced suppression autophagic clearance of p21 WAF1 and Cip1 proteins in cardiac fibroblasts."
reach
"Of interest, overexpression of UCH-L1 enhanced the PDGF-BB-induced posttranscriptional upregulation of p21 WAF1 and Cip1 protein in cardiac fibroblasts (XREF_FIG), suggesting that UCH-L1 inhibits cardiac fibroblast proliferation via posttranscriptional enhancing the expression of p21 WAF1 and Cip1 to suppress the transition of G1 to S phase."
reach
"These results suggest that UCH-L1 facilitates autophagic degradation of p21 WAF1 and Cip1 to suppress proliferation of cardiac fibroblasts in chronically pressure overloaded heart, potentially acting as a novel feedback mechanism in the regulation of maladaptive cardiac remodeling and dysfunction."
UCHL1 affects apoptotic process
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UCHL1 activates apoptotic process.
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48
UCHL1 inhibits apoptotic process.
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UCHL1 inhibits apoptotic process. 10 / 20
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"However, several E3 ligases such as HectH9, Mdm2, TNF receptor‐associated factor 6 (TRAF6; tumour necrosis factor receptor‐associated factor 6), cIAP1/2 (cellular inhibitor of apoptosis protein 1/2), CHIP, Parkin, UCHL1, TRAF2, ITCH and NEDD4‐2 specifically catalyse the K63‐linked ubiquitination.17, 18, 19 Interestingly, HectH9, Mdm2, RNF8 (ring finger protein 8) and cIAP1/2 catalyse both K63‐ and K48‐linked ubiquitination."
sparser
"Western blotting of cell death signalling components at 4 h following SE revealed that inhibition of UCHL1 (prior to SE) was associated with increased expression of nuclear p53 (Kruskal-Wallis test, P = 0.0004; Dunn’s multiple comparisons test, P < 0.01 compared to non-SE control, xref ) and cleaved MDM2 (Mann-Whitney U, P = 0.0303, compared to vehicle SE, xref )."
reach
"The results indicated that probably the extrinsic (Fas, Fas-L, Trail, DR4 and DR5) and intrinsic (cytochrome C) apoptotic pathways, the activation of p53 (phospho-Mdm-2 and phospho-p53) and the Bcl-2 family members (pro apoptotic member Bax, anti-apoptotic members Bcl-2 and Bcl-xL) combined with each other, participating in the process of apoptosis induced by UCH-L1 in MCF7 cells."
reach
"However, while exploring the relationship between UCH-L1 and p53 ubiquitination, it is important to keep in mind that, despite hypotheses to the contrary [XREF_BIBR, XREF_BIBR], it is unlikely that UCH-L1 directly deubiquitinates or ubiquitinates p53 based on what is known about UCH-L1 structure and function [XREF_BIBR, XREF_BIBR]."
reach
"Our previous work demonstrated that UCHL1 could activate the p14ARF-p53 signaling pathway by deubiquitinating p53 and p14ARF as well as ubiquitinating MDM2, which might be through its two opposing enzyme activities, hydrolase and ligase, further resulting in its tumor suppressive role in NPC tumorigenesis XREF_BIBR, XREF_BIBR."
reach
"As P53 protein is regulated through ubiquitin dependent degradation in tumorigenesis, UCHL1 promotes p53 signaling by deubiquitinating p53 and p14 ARF and ubiquitinating MDM2 for further MDM2 degradation and p53 stabilization, thus involved in NPC pathogenesis as a functional TSG XREF_BIBR."
reach
"On the contrary, UCH-L1 elevates p53 levels in MDA-MB-231 and HONE1 cells, which express DNA binding domain mutant p53 with little to no transcriptional activity [XREF_BIBR - XREF_BIBR] and LNCaP cells, which have also been reported to express DNA binding domain mutant p53 [XREF_BIBR], although this is controversial [XREF_BIBR]."
sparser
"However, while exploring the relationship between UCH-L1 and p53 ubiquitination, it is important to keep in mind that, despite hypotheses to the contrary [ xref , xref ], it is unlikely that UCH-L1 directly deubiquitinates or ubiquitinates p53 based on what is known about UCH-L1 structure and function [ xref , xref ]."
sparser
"Initially, the most Figure 7 An overlay of X-ray structures of apo UCHL1 (2ETL, yellow (light grey in the print version)) and UCHL1 bound to ubiquitin VME (3KW5, enzyme is purple (dark grey in the print version) and ubiquitin VME is green (grey in the print version)).
commonly used substrate was ubiquitin coupled via its carboxy-terminus onto the amino group of the fluorescent tag 7-amino-4-methylcoumarin (Ub-AMC)."
sparser
"Analog 34 inhibited HA-Ub-VME complex formation with UCHL1 in a dose-dependent manner ( xref B, top panel) and demonstrated selectivity over other DUBs in SW1271 cells as the only band in the HA-blot to exhibit significant dose-dependent signal reduction was the Ub-UCHL1 band ( xref B, bottom panel)."
sparser
"In contrast, the impacts of ubiquitin binding to UCH-L1 and -L3 are mostly limited to the conformational rearrangements in the cross-over loops and flanking regions, and, in the case of UCH-L1, a cascade of side-chain movements to align catalytic residues into a productive configuration xref xref ."
reach
"Indeed, the addition of 1.2 molar equivalent of ubiquitin slightly increased the thermal stability of UCH-L1 and -L3, raising the melting temperature by 2.2 +/-0.1 degreesC and 0.9 +/-0.2 degreesC, respectively, while no significant change in thermal stability was observed for UCH-L5 N240 (XREF_SUPPLEMENTARY)."
sparser
"Importantly, because we screened a human library with a mouse RNA, it was necessary to verify that human and murine ILF3 proteins share 92% identity and 95% homology and that the dsRBM2 is identical in the 2 species (unpublished results), suggesting our data are representative of AS Uchl1–ILF3 interaction in the mouse."
UCHL1 affects Neoplasm Metastasis
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UCHL1 activates Neoplasm Metastasis.
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UCHL1 inhibits Neoplasm Metastasis.
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UCHL1 affects Neoplasm Invasiveness
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UCHL1 activates Neoplasm Invasiveness.
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UCHL1 inhibits Neoplasm Invasiveness.
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5
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"Taken together, our studies show a causative link between the excessive mitochondrial turnover and the NH2htau induced in vitro neuronal death, suggesting that pathogenetic tau truncation may contribute to synaptic deterioration in AD by aberrant recruitment of Parkin and UCHL-1 to mitochondria making them more prone to detrimental autophagic clearance."
sparser
"Although the association of parkin and UCHL1 mutations with familial parkinsonism supports a link between the UPS and PD, it is apparent that the involvement of the UCHL1 I93M mutation in PD pathogenesis has become contentious in recent years as its occurrence to date is restricted to the pair of German siblings [ xref ]."
sparser
"We next performed in vitro ubiquitination analyses with recombinant proteins to test if UCH-L1 is ubiquitinated by parkin in the presence of various E2 ubiquitin-conjugating enzymes (UbcH7, UbcH8, or the Ubc13/Uev1a complex) which are known to facilitate parkin E3 ligase activity [ xref ]."
reach
"We next performed in vitro ubiquitination analyses with recombinant proteins to test if UCH-L1 is ubiquitinated by parkin in the presence of various E2 ubiquitin conjugating enzymes (UbcH7, UbcH8, or the Ubc13 and Uev1a complex) which are known to facilitate parkin E3 ligase activity [XREF_BIBR]."
reach
"As epidermal growth factor receptor (EGFR) is a known suppressor of ER transcription [42] and UCHL1 may modulate EGFR expression [43], Chen et al. chose to explore a possible role for EGFR in modulation of ER expression by UCHL1 using EGFR overexpression or silencing experiments in ER− and ER+ cell lines [41, 42]."
reach
"As expected, overexpression of UCHL1 significantly enhanced cardiomyocyte size, the mRNA level of ANF, and the protein levels of EGFR, and phosphorylated EGFR, AKT, and EKR1/2 compared with coinfection with Ad-GFP and siRNA-control after PE stimulation; moreover, this effect was markedly attenuated by coinfection with Ad-GFP or Ad-UCHL1 and siRNA-EGFR."
reach
"To further examine whether overexpression of UCHL1 in cardiomyocytes accelerates hypertrophy and dysfunction by influencing the stability of EGFR in vivo, we generated cardiomyocyte specific UCHL1 overexpressing and EGFR knockdown mice by injection with rAAV9-UCHL1 and rAAV9-siEGFR or their corresponding controls because EGFR full-knockout mice exhibit embryonic lethality."
reach
"Here, we demonstrated similar mechanisms in NB cells that UCHL1 inhibition dramatically inhibited the phosphorylation of AKT at Ser473 and ERK1/2 at Thr202/Tyr204 after RA administration, indicating that the effect of UCHL1 inhibition on RA-induced neuronal differentiation was associated with repression of AKT and ERK1/2 activities.UCHL1 has been reported positively or negatively regulating cell proliferation [34]."
reach
"Here, we demonstrated similar mechanisms in NB cells that UCHL1 inhibition dramatically inhibited the phosphorylation of AKT at Ser473 and ERK1/2 at Thr202/Tyr204 after RA administration, indicating that the effect of UCHL1 inhibition on RA-induced neuronal differentiation was associated with repression of AKT and ERK1/2 activities.UCHL1 has been reported positively or negatively regulating cell proliferation [34]."
reach
"Here, we demonstrated similar mechanisms in NB cells that UCHL1 inhibition dramatically inhibited the phosphorylation of AKT at Ser473 and ERK1/2 at Thr202/Tyr204 after RA administration, indicating that the effect of UCHL1 inhibition on RA-induced neuronal differentiation was associated with repression of AKT and ERK1/2 activities.UCHL1 has been reported positively or negatively regulating cell proliferation [34]."
reach
"While UCH-L1 has been shown to inhibit alpha 2 -adrenergic receptor (AR) agonist mediated activation of ERK via a direct association with alpha 2A -AR receptor implicating a role of UCH-L1 in neuro-protection XREF_BIBR, it has also been documented that UCH-L1 up-regulates oncogenic beta-catenin and TCF and Akt signaling to induce tumor cell proliferation and migration contributing to tumor progression XREF_BIBR, XREF_BIBR."
sparser
"To determine whether accumulation of SNO-Uch-L1 in human AD brain might be of pathophysiological significance, we calculated the ratio of SNO-Uch-L1 (by biotin-switch assay) to total Uch-L1 (as quantified from immunoblots), using methods previously described ( xref , xref , xref )."
sparser
"Indeed, S-nitrosylation of Uch-L1 occurred in a neuronal cell-based model upon exposure to Aβ oligomers -- incubation of primary rat cerebrocortical cultures in 500 nM Aβ 1–42 oligomers resulted in formation of SNO-Uch-L1 as determined by the biotin-switch assay ( xref and xref )."
UCHL1 increases the amount of UCHL1.
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13
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"The authors found that removal of a structural motif containing a short hairpin abolishes the ability of AS Uchl1 to upregulate UCHL1 protein levels, highlighting the importance of specific structural determinants of the SINE B2 sequence in the functionality of AS Uchl1 (Podbevšek et al., 2018)."
UCHL1 inhibits UCHL1.
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3
UCHL1 decreases the amount of UCHL1.
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4
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"XREF_BIBR Also, it has been demonstrated that ciRS-7 can repress Alzheimer 's disease (AD) development by suppressing NF-kappaB protein synthesis and inducing its cytoplasmic localization, promoting UCHL1 expression and UCHL1 induced amyloid precursor protein (APP) and BACE1 ubiquitination and degradation."
UCHL1 activates UCHL1.
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eidos
"In contrast , when CSMN are retrogradely transduced with AAV2-UCHL1-IRES-eGFP , which leads to the expression of both GFP and UCHL1 proteins , high level of UCHL1 expression is detected only in GFP + transduced CSMN ( Fig. 5d , g ) , confirming effective transduction and directed gene delivery only to CSMN ."
sparser
"Expression level: log2(FPKM+0.01). (C) Preventive images of ccRCC tissues and normal renal tissues incubated with UCHL1, CD36, HMGB3, IKBKE, PTLP and PTGES anti-body. (D) ROC curve analyses for evaluating the diagnostic potential of UCHL1, CD36 and HMGB3 for ccRCC. (E) ROC curve analyses for evaluating the diagnostic potential of UCHL1-CD36, UCHL1 -HMGB3, and HMGB3-CD36 for ccRCC. (F) ROC curve analyses for evaluating the diagnostic potential of UCHL1-CD36-HMGB3 for ccRCC."
reach
"Using an elegant screening approach to identify factors that would lead to HIF-1 transcriptional activity under normoxic conditions, Goto et al. recently identified the ubiquitin C-terminal hydrolase-L1 (UCHL1) as a HIF-1 deubiquitinating enzyme that promotes HIF-1 activity under normoxic and hypoxic conditions by preventing VHL mediated degradation of HIF-1 (XREF_FIG)."
sparser
"Since both LMP1 ( xref ) and UCH-L1 ( xref ) have been shown to be membrane-anchored cellular molecules, and since C-terminal farnesylation regulates UCH-L1 association with cellular membranes ( xref ), we asked whether the C-terminal farnesylation of UCH-L1 is involved in the formation of complexes between LMP1 and UCH-L1."
reach
"However, because LMP1 levels are low in dually infected PEL cells, and knockdown of LMP1 did not completely abrogate the increase in uch-l1 expression observed in BC-1 cells compared to BC-3 cells, these findings can not eliminate the possibility that EBNA1 or EBV encoded non polyadenylated RNAs (EBER1 and EBER2) contribute to the up-regulation of uch-l1."
reach
"The finding that KSHV LANA can itself induce the expression of EBV LMP1 suggests there is a second mechanism through which UCH-L1 levels are augmented in co-infected cells : LANA activates the expression of LMP1, which in turn activates the uch-l1 promoter, resulting in greater levels of UCH-L1."
UCHL1 affects Parkinson Disease
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UCHL1 activates Parkinson Disease.
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UCHL1 activates Parkinson Disease. 10 / 19
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Mutated UCHL1 activates Parkinson Disease. 2 / 2
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UCHL1 inhibits Parkinson Disease.
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UCHL1 binds Parkinson Disease.
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reach
"Taken together, our studies show a causative link between the excessive mitochondrial turnover and the NH2htau induced in vitro neuronal death, suggesting that pathogenetic tau truncation may contribute to synaptic deterioration in AD by aberrant recruitment of Parkin and UCHL-1 to mitochondria making them more prone to detrimental autophagic clearance."
sparser
"Although the association of parkin and UCHL1 mutations with familial parkinsonism supports a link between the UPS and PD, it is apparent that the involvement of the UCHL1 I93M mutation in PD pathogenesis has become contentious in recent years as its occurrence to date is restricted to the pair of German siblings [ xref ]."
sparser
"Western blotting of cell death signalling components at 4 h following SE revealed that inhibition of UCHL1 (prior to SE) was associated with increased expression of nuclear p53 (Kruskal-Wallis test, P = 0.0004; Dunn’s multiple comparisons test, P < 0.01 compared to non-SE control, xref ) and cleaved MDM2 (Mann-Whitney U, P = 0.0303, compared to vehicle SE, xref )."
UCHL1 affects cell migration
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UCHL1 activates cell migration.
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UCHL1 inhibits cell migration.
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UCHL1 affects translation
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UCHL1 activates translation.
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UCHL1 inhibits translation.
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sparser
"To fully elucidate the physiological and pathophysiological importance of deubiquitination, it is critical to more thoroughly analyse the meaning of our immunoprecipitation data in which UCHL1 bound to HIF-1α and prevented VHL from directly interacting with HIF-1α ( xref ) and the interaction between UCHL1 and HIF-1α was facilitated under hypoxic conditions ( xref )."
reach
"To fully elucidate the physiological and pathophysiological importance of deubiquitination, it is critical to more thoroughly analyse the meaning of our immunoprecipitation data in which UCHL1 bound to HIF-1alpha and prevented VHL from directly interacting with HIF-1alpha (XREF_FIG) and the interaction between UCHL1 and HIF-1alpha was facilitated under hypoxic conditions (XREF_FIG)."
sparser
"Expression level: log2(FPKM+0.01). (C) Preventive images of ccRCC tissues and normal renal tissues incubated with UCHL1, CD36, HMGB3, IKBKE, PTLP and PTGES anti-body. (D) ROC curve analyses for evaluating the diagnostic potential of UCHL1, CD36 and HMGB3 for ccRCC. (E) ROC curve analyses for evaluating the diagnostic potential of UCHL1-CD36, UCHL1 -HMGB3, and HMGB3-CD36 for ccRCC. (F) ROC curve analyses for evaluating the diagnostic potential of UCHL1-CD36-HMGB3 for ccRCC."
sparser
"When hSOD1 G93A mice—the golden standard for ALS drug discovery efforts for the past 15 years—are crossed with UCHL1-eGFP reporter mice to generate hSOD1 G93A -UeGFP ALS reporter mouse model, a significant reduction in the number CSMN was observed, but in the spinal cord, eGFP expression was restricted mostly to S and gamma SMN resistant to degeneration in ALS for unknown reasons [ xref ]."
sparser
"We recently generated a reporter line for UMNs, UCHL1‐eGFP mice, in which UMNs are genetically labeled with eGFP expression that is stable and long lasting, xref so that their cellular responses to compound treatment can be quantitatively assessed both in vitro and in vivo . xref , xref In an effort to visualize diseased UMNs and to assess their cellular response to compound treatment, hSOD1 G93A xref and the TDP‐43 A315T mice xref were crossed with UCHL1‐eGFP to generate UMN reporter disease models, hSOD1 G93A ‐UeGFP and prpTDP‐43 A315T ‐UeGFP mice, in which UMNs with mSOD1 toxicity and TDP‐43 pathology were labeled with eGFP expression. xref NU‐9 (Figure xref ) was delivered to both hSOD1 G93A ‐UeGFP and WT‐UeGFP mice (Figure xref , Table S2) at two different doses (20 and 100 mg/kg/day) daily via oral gavage starting at P60, when mice begin to show symptoms and UMNs display cellular defects. xref All mice were sacrificed at P120, which is considered end stage and about 60% of UMNs in the motor cortex are lost while the remaining UMNs have smaller soma size and vacuolated and disintegrated apical dendrites. xref "
sparser
"hSOD1 G93A -UeGFP mice were previously generated by crossing hSOD1 G93A with UCHL1-eGFP mice ( xref a) after CSMN identity of eGFP+ neurons in layer 5 of the motor cortex were confirmed and the numbers of GFP+ CSMN were significantly reduced with disease progression starting at P90 [ xref ]."
sparser
"To visualize diseased UMNs and to assess their cellular response to compound treatment, TDP‐43 A315T mice xref were crossed with UCHL1‐eGFP mice xref to generate an UMN reporter disease model prpTDP‐43 A315T ‐UeGFP mice. xref There is no misfolded SOD1 detected in the UMN of prpTDP‐43 A315T ‐UeGFP mice (Figure S3), and there is no TDP‐43 pathology reported in SOD1 mouse models or patients with SOD1 mutations, xref , xref , xref , xref , xref , xref in fact mSOD1 toxicity and TDP‐43 pathology are accepted to be distinct causes of motor neuron degeneration."
reach
"While UCH-L1 has been shown to inhibit alpha 2 -adrenergic receptor (AR) agonist mediated activation of ERK via a direct association with alpha 2A -AR receptor implicating a role of UCH-L1 in neuro-protection XREF_BIBR, it has also been documented that UCH-L1 up-regulates oncogenic beta-catenin and TCF and Akt signaling to induce tumor cell proliferation and migration contributing to tumor progression XREF_BIBR, XREF_BIBR."
UCHL1 affects cell cycle
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UCHL1 inhibits cell cycle.
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UCHL1 activates cell cycle.
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sparser
"Since both LMP1 ( xref ) and UCH-L1 ( xref ) have been shown to be membrane-anchored cellular molecules, and since C-terminal farnesylation regulates UCH-L1 association with cellular membranes ( xref ), we asked whether the C-terminal farnesylation of UCH-L1 is involved in the formation of complexes between LMP1 and UCH-L1."
reach
"The results showed that, Jab1 and p27 (kip1), in parallel to Uchl1, increased in spermatocytes of apoptotic appearances in response to heat-stress, but not in multinucleated giant cells; Jab1 bound to Uchl1 in testis protein extracts, and co-localized with Uchl1 and p27 (kip1) specifically in spermatocytes with apoptotic appearances."
reach
"The results showed that, Jab1 and p27 (kip1), in parallel to Uchl1, increased in spermatocytes of apoptotic appearances in response to heat-stress, but not in multinucleated giant cells; Jab1 bound to Uchl1 in testis protein extracts, and co-localized with Uchl1 and p27 (kip1) specifically in spermatocytes with apoptotic appearances."
UCHL1 affects cell growth
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UCHL1 inhibits cell growth.
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UCHL1 inhibits cell growth. 9 / 10
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"Ectopic UCHL1 expression in breast tumor cells suppresses cell growth, induces G0/G1 arrest and apoptosis through disrupting p53 signaling, depending on its deubiquitinase (DUB) activity, suggesting that UCHL1 is a functional tumor suppressor and potential tumor marker for this cancer."
UCHL1 activates cell growth.
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sparser
"To further validate the interaction between UCHL1 and CTTN, we performed endogenous immunoprecipitation experiments in NP69 cells which is of highly enriched of UCHL1 and found that two proteins at the endogenous levels bound to each other, which confirmed that UCHL1 and CTTN still have interaction ( xref F)."
reach
"In the present study, there are several novel findings regarding UCH-L1 as a negative regulator of maladaptive cardiac remodeling and dysfunction as follows : (i) UCH-L1 expression is enhanced in cardiac myocytes and fibroblasts during the earlier stage of cardiac adaptive hypertrophy and declined in the process of maladaptive responses to the sustained hemodynamic stress; (ii) UCH-L1 inhibits cardiac fibroblast proliferation via suppressing PDGF and PDGFRbeta signaling; (iii) UCH-L1 preferentially enhances PDGF-BB-induced suppression autophagic clearance of p21 WAF1 and Cip1 proteins in cardiac fibroblasts."
reach
"Of interest, overexpression of UCH-L1 enhanced the PDGF-BB-induced posttranscriptional upregulation of p21 WAF1 and Cip1 protein in cardiac fibroblasts (XREF_FIG), suggesting that UCH-L1 inhibits cardiac fibroblast proliferation via posttranscriptional enhancing the expression of p21 WAF1 and Cip1 to suppress the transition of G1 to S phase."
reach
"To explore the underlying mechanism by which UCH-L1 enhances PDGF-BB-induced posttranscriptional upregulation of p21 WAF1 and Cip1, we determined a potential role of UCH-L1 in regulating p21 clearance by UPS and autophagy, two major pathways in the posttranscriptional control of protein levels XREF_BIBR."
reach
"To explore the underlying mechanism by which UCH-L1 enhances PDGF-BB-induced posttranscriptional upregulation of p21 WAF1 and Cip1, we determined a potential role of UCH-L1 in regulating p21 clearance by UPS and autophagy, two major pathways in the posttranscriptional control of protein levels XREF_BIBR."
reach
"In the present study, there are several novel findings regarding UCH-L1 as a negative regulator of maladaptive cardiac remodeling and dysfunction as follows : (i) UCH-L1 expression is enhanced in cardiac myocytes and fibroblasts during the earlier stage of cardiac adaptive hypertrophy and declined in the process of maladaptive responses to the sustained hemodynamic stress; (ii) UCH-L1 inhibits cardiac fibroblast proliferation via suppressing PDGF and PDGFRbeta signaling; (iii) UCH-L1 preferentially enhances PDGF-BB-induced suppression autophagic clearance of p21 WAF1 and Cip1 proteins in cardiac fibroblasts."
reach
"Of interest, overexpression of UCH-L1 enhanced the PDGF-BB-induced posttranscriptional upregulation of p21 WAF1 and Cip1 protein in cardiac fibroblasts (XREF_FIG), suggesting that UCH-L1 inhibits cardiac fibroblast proliferation via posttranscriptional enhancing the expression of p21 WAF1 and Cip1 to suppress the transition of G1 to S phase."
reach
"However, in the presence of MG132, PDGF-BB was still able to upregulate p21 WAF1 and Cip1 protein levels while overexpression of UCH-L1 enhanced not only the PDGF-BB-induced upregulation of p21 WAF1 and Cip1 protein in presence of MG132 but also the basal increased p21 WAF1 and Cip1 protein level induced by MG132 per se (XREF_FIG, XREF_SUPPLEMENTARY)."
sparser
"To further validate the interaction between UCHL1 and CTTN, we performed endogenous immunoprecipitation experiments in NP69 cells which is of highly enriched of UCHL1 and found that two proteins at the endogenous levels bound to each other, which confirmed that UCHL1 and CTTN still have interaction ( xref F)."
UCHL1 affects cell death
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UCHL1 inhibits cell death.
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UCHL1 inhibits cell death. 7 / 7
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"UCHL1 mediated cell death can be attenuated by mitochondrial protein HTRA2 [XREF_BIBR], ATP13A2 regulates mitochondrial bioenergetics through macroautophagy [XREF_BIBR], VPS35 mediates vesicle transport between mitochondria and peroxisomes [XREF_BIBR], and EIF4G1 is involved in stress related protection of mitochondria [XREF_BIBR]."
reach
"In this study we demonstrated that Uch-L1 inhibition induces BACE1 up-regulation and increases neuronal and apoptotic cell death in control as well as in transgenic AD mouse model subjected to Bengal Rose, a light sensitive dye inducing that induces a cortical infarction through photo activation."
UCHL1 activates cell death.
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UCHL1 activates cell death. 6 / 6
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"To determine whether a decrease in UCH-L1 exacerbates h-IAPP-induced apoptosis, we transfected INS 832/13 cells with UCH-L1 siRNA or scramble (25 nmol/l, 36 h) and transduced these cells with h-IAPP or r-IAPP adenoviruses at 300 MOI for 30 h. Under these conditions, neither UCH-L1 siRNA nor h-IAPP alone induced cell death as illustrated by cleaved caspase-3 and cleaved PARP levels or caspase-3 activity (data not shown)."
reach
"The caspase mediated apoptosis in E-64-treated fibroblasts was reversed by transfection with a UCH-L1 plasmid, and increased after downregulation of UCH-L1 by siRNA, suggesting that UCH-L1 deficiency and impairment of the ubiquitin dependent protein degradation pathway can contribute to the increased cell death observed in many lysosomal storage disorders."
reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."
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
"In a contrasting analysis, Liu et al. proposed that UCHL1 promotes breast cancer metastasises by deubiquitinating and stabilising TGFβR1 and SMAD2 in TNBC by maintaining the TGF-β signalling pathway [54], with UCHL1 inhibition using a cyanpyrrolidine-based covalent inhibitor 6RK73 or genetic knockdown antagonising TGF-β signalling in TNBC models."
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."
reach
"Even though UCHL1 negatively regulates ER expression through the stabilisation of EGFR and subsequent hyperactivation of MAPK signalling, direct EGFR and/or MAPK silencing or inhibition were not explored by Chen et al. to elucidate their effects on ER expression and endocrine therapy in breast cancer cell lines with modulated UCHL1 expression [41]."
reach
"As epidermal growth factor receptor (EGFR) is a known suppressor of ER transcription [42] and UCHL1 may modulate EGFR expression [43], Chen et al. chose to explore a possible role for EGFR in modulation of ER expression by UCHL1 using EGFR overexpression or silencing experiments in ER− and ER+ cell lines [41, 42]."
reach
"It is not clear from these studies whether UCHL1 modulates ER expression and TGF-β signalling simultaneously or in a context-specific manner, as the ER expression study was conducted in ER− breast cancers, whereas the regulation of TGF-β signalling study was performed only in TNBC."
reach
"Growing evidence demonstrates that high UCHL1 activity in specific classes of breast cancers, including ER− breast cancer and TNBC, can be targeted to enhance the efficacy of endocrine therapy in ER− breast cancer cells, as well as to mitigate TNBC migration and metastasis [41, 54]."
eidos
"It is not clear from these studies whether UCHL1 modulates ER expression and TGF-beta signalling simultaneously or in a context-specific manner , as the ER expression study was conducted in ER - breast cancers , whereas the regulation of TGF-beta signalling study was performed only in TNBC ."
sparser
"In contrast, immunostaining for the cell cycle regulator p27 Kip1 , which has previously been associated with PGP9.5 in lung cancer cells, revealed transient downregulation of p27 Kip1 in naphthalene exposed airways compared to controls, indicating that the rise in PGP9.5 in the airway epithelium is related to downregulation of p27 Kip1 ."
UCHL1 affects Alzheimer Disease
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UCHL1 inhibits Alzheimer Disease.
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UCHL1 binds Alzheimer Disease.
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UCHL1 activates Alzheimer Disease.
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sparser
"In contrast, immunostaining for the cell cycle regulator p27 Kip1 , which has previously been associated with PGP9.5 in lung cancer cells, revealed transient downregulation of p27 Kip1 in naphthalene exposed airways compared to controls, indicating that the rise in PGP9.5 in the airway epithelium is related to downregulation of p27 Kip1 ."
UCHL1 affects reactive oxygen species
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UCHL1 increases the amount of reactive oxygen species.
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UCHL1 activates reactive oxygen species.
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UCHL1 binds reactive oxygen species.
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UCHL1 affects monoubiquitin
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6
reach
"The major findings of this study are (1) CyPGs such as 15dPGJ2 adduct the C152 of UCH-L1 and mutation of the C152 of UCH-L1 attenuates the loss of hydrolase activity after 15dPGJ2 treatment; (2) the UCH-L1 C152A mutation decreases 15dPGJ2 induced accumulation and aggregation of UCH-L1 and ubiquitinated proteins in primary neurons; and (3) primary neurons derived from UCH-L1-C152A mutant mice are resistant to cell death and neurite injury induced by treatment with 15dPGJ2."
LDN-57444 affects UCHL1
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sparser
"To fully elucidate the physiological and pathophysiological importance of deubiquitination, it is critical to more thoroughly analyse the meaning of our immunoprecipitation data in which UCHL1 bound to HIF-1α and prevented VHL from directly interacting with HIF-1α ( xref ) and the interaction between UCHL1 and HIF-1α was facilitated under hypoxic conditions ( xref )."
reach
"To fully elucidate the physiological and pathophysiological importance of deubiquitination, it is critical to more thoroughly analyse the meaning of our immunoprecipitation data in which UCHL1 bound to HIF-1alpha and prevented VHL from directly interacting with HIF-1alpha (XREF_FIG) and the interaction between UCHL1 and HIF-1alpha was facilitated under hypoxic conditions (XREF_FIG)."
CPKCgamma affects UCHL1
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11
reach
"Additionally, to evade host innate immunity, Hr-HPV can inhibit PRR signaling through the induction of ubiquitin C-terminal hydrolase L1 (UCHL1) expression; UCHL1 blocks the activation of NF-kappaB and IRF3, both of which are transcription factors that induce the production of proinflammatory cytokines and chemokines XREF_BIBR."
reach
"Overexpression of the UCHL1 gene significantly attenuated tumor necrosis factor (TNF)-alpha-induced NF-kappaB activity in vascular cells and increased inhibitor of kappa B-alpha (IkappaB-alpha), possibly through the attenuation of IkappaB-alpha ubiquitination, leading to decreased neointima in the balloon injured artery."
reach
"These data together suggest that UCHL1 also negatively regulates the NF-kappaB and STAT1 pathway to inhibit the immunosuppressive capacity and IDO expression of human MSCs, indicating an essential role of UCHL1 to regulate the immunosuppressive capacity of both human and murine MSCs."
LDN affects UCHL1
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11
reach
"To provide the intrinsic mechanism of UCH-L1 upregulation in HG stimulated podocytes, podocyte cells were treated with HG for 24 or 48 h, after preincubated with or without recombinant Dickkopf-1 (DKK1) protein, a secreted Wnt antagonist that can specially block the canonical Wnt signaling [XREF_BIBR]."
UCHL1 affects proteolysis
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UCHL1 activates proteolysis.
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UCHL1 activates proteolysis. 8 / 8
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reach
"Our data suggest that UCHL1 upregulation in ACTN4 associated FSGS fuels the proteasome and that UCHL1 deletion may impair proteolysis and thereby preserve K256E and wt-alpha-actinin -4 heterodimers, maintaining podocyte cytoskeletal integrity and protecting the glomerular filtration barrier."
UCHL1 inhibits proteolysis.
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UCHL1 inhibits proteolysis. 2 / 2
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2
reach
"Our data also suggest that ciRS-7 modulates APP and BACE1 levels in a nuclear factor-kappaB (NF-kappaB)-dependent manner : ciRS-7 expression inhibits translation of NF-kappaB and induces its cytoplasmic localization, thus derepressing expression of UCHL1, which promotes APP and BACE1 degradation."
reach
"Specifically, UCH-L1 appears to increase lysosomal degradation of BACE1, as inhibition of UCH-L1 caused a significant increase in BACE1 protein levels in several cell types, and loss of UCH-L1 gene function in gad mice significantly increased levels of endogenous BACE1, C99, and Abeta peptides [XREF_BIBR, XREF_BIBR]."
reach
"In this study we demonstrated that Uch-L1 inhibition induces BACE1 up-regulation and increases neuronal and apoptotic cell death in control as well as in transgenic AD mouse model subjected to Bengal Rose, a light sensitive dye inducing that induces a cortical infarction through photo activation."
Valproic acid affects UCHL1
9
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sparser
"In a controlled cortical impact (CCI) injury model of post-traumatic brain injury, TAT-UCHL1 treatment improved function of the ubiquitin-proteasome pathway, decreased activation of autophagy after CCI, attenuated axonal injury and increased hippocampal neuronal survival after CCI [ xref ]."
reach
"Indeed, it is known that the NOS synthesis is regulated through the activation of the extracellular signal regulated protein kinase (ERK) and the UCHL1 protein has been shown to drastically decrease the activation of ERK XREF_BIBR, arguing for an inactivation of the NOS system in A. algerae infected HFF cells."
reach
"While UCH-L1 has been shown to inhibit alpha 2 -adrenergic receptor (AR) agonist mediated activation of ERK via a direct association with alpha 2A -AR receptor implicating a role of UCH-L1 in neuro-protection XREF_BIBR, it has also been documented that UCH-L1 up-regulates oncogenic beta-catenin and TCF and Akt signaling to induce tumor cell proliferation and migration contributing to tumor progression XREF_BIBR, XREF_BIBR."
UCHL1 affects Carcinogenesis
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UCHL1 activates Carcinogenesis. 9 / 9
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eidos
"The precise mechanism by which UCHL1 contributes to tumorigenesis remains unclear , although reports suggest that it contributes to cell survival signalling , cell cycle regulation , DNA repair and regulating pools of free ubiquitin in ways that affect protein degradation and function115 ."
reach
"The precise mechanism by which UCHL1 contributes to tumorigenesis remains unclear, although reports suggest that it contributes to cell survival signalling, cell cycle regulation, DNA repair and regulating pools of free ubiquitin in ways that affect protein degradation and function ."
sparser
"In a controlled cortical impact (CCI) injury model of post-traumatic brain injury, TAT-UCHL1 treatment improved function of the ubiquitin-proteasome pathway, decreased activation of autophagy after CCI, attenuated axonal injury and increased hippocampal neuronal survival after CCI [ xref ]."
Monoubiquitin affects UCHL1
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UCHL1 affects VER
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UCHL1 affects IR
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sparser
"Notably, while our previous work showed that early life VNC increases the density of LCs exhibiting PGP9.5-IR during adolescence, the density in adulthood was similar between the groups receiving VNC and vehicle as neonates (n = 6–8 in each group; U = 20.5; p = 0.686; Mann-Whitney test; xref ), further suggesting recovery from the neonatal VNC exposure."
sparser
"Although most of the studies on PGP 9.5 neuronal density use the experimental models, da Silveira et al. [ xref ] and Martins et al. [ xref ] showed that patients chronically infected with megacolon presented reduced density of IR-PGP 9.5 nerve fibers in both, internal muscle layer and intestinal external muscle, as compared to nonmegacolon CD patients and noninfected."
sparser
"Furthermore, an FDA-approved glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 (GFAP-UCH-L1) test to detect intracranial abnormalities [ xref ] is currently in use in Scandinavian countries, and it has recently been validated in the Finnish population [ xref ]."
| PMC
reach
"Moreover, and identical to podocyte death caused by UCH-L1 overexpression, the addition of zVAD-fmk did not prevent TNF induced cell death, demonstrating that TNF indeed elicits necroptosis in podocytes, and that UCH-L1 represents a downstream mediator of the necroptotic signaling cascade of TNF also in podocytes."
reach
"We and others have previously observed this effect of zVAD-fmk in necroptosis [XREF_BIBR, XREF_BIBR, XREF_BIBR], excluding that de novo expression and thus increased UCH-L1 activity causes death of podocytes by apoptosis but rather pointing to programmed necrosis and necroptosis as the responsible suicide program."
N-acetyl-beta-D-galactosaminyl-(1->4)-N-acetyl-D-glucosaminyl group affects UCHL1
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8
IR affects UCHL1
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sparser
"Notably, while our previous work showed that early life VNC increases the density of LCs exhibiting PGP9.5-IR during adolescence, the density in adulthood was similar between the groups receiving VNC and vehicle as neonates (n = 6–8 in each group; U = 20.5; p = 0.686; Mann-Whitney test; xref ), further suggesting recovery from the neonatal VNC exposure."
sparser
"Although most of the studies on PGP 9.5 neuronal density use the experimental models, da Silveira et al. [ xref ] and Martins et al. [ xref ] showed that patients chronically infected with megacolon presented reduced density of IR-PGP 9.5 nerve fibers in both, internal muscle layer and intestinal external muscle, as compared to nonmegacolon CD patients and noninfected."
sparser
"Furthermore, an FDA-approved glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 (GFAP-UCH-L1) test to detect intracranial abnormalities [ xref ] is currently in use in Scandinavian countries, and it has recently been validated in the Finnish population [ xref ]."
| PMC
UCHL1 affects cell differentiation
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UCHL1 activates cell differentiation. 7 / 7
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2
5
reach
"These results together suggest that UCHL1 promotes neuronal differentiation of NB cells.To explore the potential molecular mechanisms by which UCHL1 promoted neuronal differentiation, we performed immunoblotting analysis to determine the activities of signaling pathways including AKT and ERK1/2, in cells."
eidos
"For example , Gao H et al. demonstrated that UCHL1 played a role in myogenesis by inhibiting differentiation [ 36 ] , while Sakura et al found that UCHL1 could regulate the morphology of neural progenitor cells and modulate their differentiation thereby enhancing neurogenesis in the embryonic brain [ 25 ] ."
reach
"Overexpression of the UCHL1 gene significantly attenuated tumor necrosis factor (TNF)-alpha-induced NF-kappaB activity in vascular cells and increased inhibitor of kappa B-alpha (IkappaB-alpha), possibly through the attenuation of IkappaB-alpha ubiquitination, leading to decreased neointima in the balloon injured artery."
reach
"Together, our results suggest that the ubiquitination of TrkB is a mechanism that controls its downstream signaling pathways via the regulation of its endocytosis and postendocytic trafficking and that UCH-L1 mediates the deubiquitination of TrkB and could be a potential target for the modulation of hippocampus dependent memory."
"Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory via Its Deubiquitinating Effect on TrkB"
reach
"Our previous work demonstrated that UCHL1 could activate the p14ARF-p53 signaling pathway by deubiquitinating p53 and p14ARF as well as ubiquitinating MDM2, which might be through its two opposing enzyme activities, hydrolase and ligase, further resulting in its tumor suppressive role in NPC tumorigenesis XREF_BIBR, XREF_BIBR."
reach
"As P53 protein is regulated through ubiquitin dependent degradation in tumorigenesis, UCHL1 promotes p53 signaling by deubiquitinating p53 and p14 ARF and ubiquitinating MDM2 for further MDM2 degradation and p53 stabilization, thus involved in NPC pathogenesis as a functional TSG XREF_BIBR."
reach
"We have shown : (i) a reduction of soluble Uch-L1 protein levels in the hippocampus of APP and PS1 mice; (ii) that inhibition of Uch-L1 activity leads to the inhibition of hippocampal LTP; and (iii) that transduction of Uch-L1 protein restores LTP in APP and PS1 mice and also reestablishes normal Uch activity, basal neurotransmission and synaptic plasticity, and improves associative memory in mice."
reach
"Our previous work demonstrated that UCHL1 could activate the p14ARF-p53 signaling pathway by deubiquitinating p53 and p14ARF as well as ubiquitinating MDM2, which might be through its two opposing enzyme activities, hydrolase and ligase, further resulting in its tumor suppressive role in NPC tumorigenesis XREF_BIBR, XREF_BIBR."
reach
"As P53 protein is regulated through ubiquitin dependent degradation in tumorigenesis, UCHL1 promotes p53 signaling by deubiquitinating p53 and p14 ARF and ubiquitinating MDM2 for further MDM2 degradation and p53 stabilization, thus involved in NPC pathogenesis as a functional TSG XREF_BIBR."
MiR-922 affects UCHL1
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6
UCHL1 affects Neoplastic Stem Cells
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6
UCHL1 activates Neoplastic Stem Cells. 6 / 6
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6
reach
"Overall, UCH-L1 activates the CSC-like properties in DU145 cells through the PI3 K/Akt pathway, whereas UCH-L3 has opposite effects.As the relapse of CRPC is attributed to CSCs, we examined the relationship between the disease-free survival and the level of UCH-L1 and UCH-L3 in prostate cancer patients."
sparser
"Importantly, because we screened a human library with a mouse RNA, it was necessary to verify that human and murine ILF3 proteins share 92% identity and 95% homology and that the dsRBM2 is identical in the 2 species (unpublished results), suggesting our data are representative of AS Uchl1–ILF3 interaction in the mouse."
UCHL1 affects Cell Survival
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5
UCHL1 inhibits Cell Survival.
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UCHL1 activates Cell Survival.
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NMDA receptor affects UCHL1
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6
sparser
"Importantly, because we screened a human library with a mouse RNA, it was necessary to verify that human and murine ILF3 proteins share 92% identity and 95% homology and that the dsRBM2 is identical in the 2 species (unpublished results), suggesting our data are representative of AS Uchl1–ILF3 interaction in the mouse."
5-aza-2'-deoxycytidine affects UCHL1
2
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Reactive oxygen species affects UCHL1
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3
Reactive oxygen species inhibits UCHL1.
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2
1
Reactive oxygen species binds UCHL1.
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2
Prostaglandins affects UCHL1
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Prostaglandins inhibits UCHL1. 5 / 5
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5
reach
"In addition, some cyclopentenone prostaglandins, such as delta12-PGJ2 and 15d-PGJ2, inhibit the activities of UCH-L1 and induce ubiquitinated protein aggregation in neuronal cells, which may provide a molecular mechanism linking inflammation with neurodegeneration [XREF_BIBR, XREF_BIBR]."
Methylmercury chloride affects UCHL1
5
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WP1130 affects UCHL1
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2
3
eidos
"For example , 8-mercapto-N - ( ( tetrahydro-3-furanyl ) methyl ) -4 - quinoline carboxamide , LND-57444 , VLX1570 , ML323 , ( ADC-01 , ADC-03 , HBX41108 , HBX19818 , P5091 , P22077 ) , 9 - ( ethoxyimino ) -9 H-indeno ( 1,2 - b ) pyrazine-2 ,3 - dicarbonitrile , WP1130 , Mitoxantrone and GSK2643943A are able to inhibit PSMD14 , UCHL1 , UCHL5 and USP14 , USP1 , USP7 , USP8 , USP9X , USP11 and USP20 , respectively ."
VAEFMK affects UCHL1
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1
4
VAEFMK binds UCHL1.
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3
reach
"Thus, the co-crystal structure shows that VAEFMK binds to UCHL1 (the compound bound structure is hereafter referred to as UCHL1-VAE thioether or simply as UCHL1-VAE) via a similar mechanism of action as that known for other FMK inhibitors that inactivate cysteine proteases, including caspases."
VAEFMK inhibits UCHL1.
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1
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4
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5
reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."
reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."
UCH-L1 inhibitor affects UCHL1
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5
UCHL1 affects glutathione
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4
Modified UCHL1 increases the amount of glutathione. 2 / 2
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UCHL1 increases the amount of glutathione. 2 / 2
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2
UCHL1 affects cellular senescence
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4
UCHL1 affects cell adhesion
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2
UCHL1 inhibits cell adhesion. 2 / 4
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2
reach
"Expression of a catalytically active UCH-L1 promoted the proliferation of a UCH-L1-negative EBV transformed lymphoblastoid cell line (LCL) and inhibited cell adhesion, whereas a catalytic mutant had no effect, confirming the requirement of UCH-L1 enzymatic activity for the regulation of these phenotypes."
UCHL1 affects angiogenesis
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3
UCHL1 affects activity
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4
sparser
"For example, we have recently shown that CyPGs can form a covalent bond with specific cysteines within UCH-L1, an enzyme within the ubiquitin–proteasome pathway, and this binding causes a conformational change within UCH-L1 that inhibits its activity and leads to accumulation of ubiquitinated proteins [ xref ]."
reach
"While UCH-L1 has been shown to inhibit alpha 2 -adrenergic receptor (AR) agonist mediated activation of ERK via a direct association with alpha 2A -AR receptor implicating a role of UCH-L1 in neuro-protection XREF_BIBR, it has also been documented that UCH-L1 up-regulates oncogenic beta-catenin and TCF and Akt signaling to induce tumor cell proliferation and migration contributing to tumor progression XREF_BIBR, XREF_BIBR."
UCHL1 affects Proteasome
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3
UCHL1 inhibits Proteasome.
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1
UCHL1 inhibits Proteasome. 1 / 2
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UCHL1 activates Proteasome.
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UCHL1 activates Proteasome. 2 / 2
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reach
"The first study to show the effect of PDE inhibition on UPS mediated degradation of disease related proteins [XREF_BIBR, XREF_BIBR] demonstrated that administration of either rolipram (a selective PDE4 inhibitor) or purified cell-permeable Uch-L1 (ubiquitin C-terminal hydrolase L1) led to proteasome mediated degradation in a mouse model of Alzheimer 's-related amyloid deposition [XREF_BIBR]."
UCHL1 affects NCIT:C118795
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4
UCHL1 affects FFA
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4
sparser
"As expected, overexpression of UCHL1 significantly enhanced cardiomyocyte size, the mRNA level of ANF, and the protein levels of EGFR, and phosphorylated EGFR, AKT, and EKR1/2 compared with coinfection with Ad-GFP and siRNA-control after PE stimulation; moreover, this effect was markedly attenuated by coinfection with Ad-GFP or Ad-UCHL1 and siRNA-EGFR (fig."
S-nitrosoglutathione affects UCHL1
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4
NCIT:C118795 affects UCHL1
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4
sparser
"Importantly, because we screened a human library with a mouse RNA, it was necessary to verify that human and murine ILF3 proteins share 92% identity and 95% homology and that the dsRBM2 is identical in the 2 species (unpublished results), suggesting our data are representative of AS Uchl1–ILF3 interaction in the mouse."
sparser
"As expected, overexpression of UCHL1 significantly enhanced cardiomyocyte size, the mRNA level of ANF, and the protein levels of EGFR, and phosphorylated EGFR, AKT, and EKR1/2 compared with coinfection with Ad-GFP and siRNA-control after PE stimulation; moreover, this effect was markedly attenuated by coinfection with Ad-GFP or Ad-UCHL1 and siRNA-EGFR (fig."
sparser
"Importantly, because we screened a human library with a mouse RNA, it was necessary to verify that human and murine ILF3 proteins share 92% identity and 95% homology and that the dsRBM2 is identical in the 2 species (unpublished results), suggesting our data are representative of AS Uchl1–ILF3 interaction in the mouse."
6RK73 affects UCHL1
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2
Ubiquitin VME affects UCHL1
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3
Sodium arsenite affects UCHL1
3
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Nitric oxide affects UCHL1
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3
Nicotine affects UCHL1
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3
reach
"Our data showed that elevated serum levels of UCHL1 were significantly correlated with increased cBMECs in the animals treated with gp120 and nicotine, suggesting that this protein could be used as a new molecular biomarker for BBB injury caused by microbial and non microbial factors."
reach
"Our results showed that nicotine and gp120 were able to increase blood levels of both molecular (UCHL1 and S100B) and cellular (cBMECs and EPCs) markers (XREF_FIG), suggesting that UCHL1 is a potential new biomarker for BBB disorders caused by drugs of abuse and microbial factors."
Naphthalene affects UCHL1
2
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1
Mono-Ub affects UCHL1
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3
Benzo[a]pyrene affects UCHL1
3
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UCHL1 affects ubiquitin VME
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3
UCHL1 affects necroptotic process
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UCHL1 activates necroptotic process. 1 / 3
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UCHL1 affects ligase
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UCHL1 affects endoplasmic reticulum
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3
UCHL1 affects doxorubicin
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3
UCHL1 affects breast cancer metastasis
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3
UCHL1 affects VAEFMK
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3
reach
"Thus, the co-crystal structure shows that VAEFMK binds to UCHL1 (the compound bound structure is hereafter referred to as UCHL1-VAE thioether or simply as UCHL1-VAE) via a similar mechanism of action as that known for other FMK inhibitors that inactivate cysteine proteases, including caspases."
UCHL1 affects TβRI
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3
UCHL1 affects RA-induced neural differentiation NB tumor cells
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3
UCHL1 affects NCIT:C114489
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3
UCHL1 affects Histone_H2B
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3
UCHL1 affects DOX-resistance
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3
UCHL1 affects CyPG
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3
UCHL1 affects CD45RO
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3
sparser
"With “Parkinson’s disease” serving as the keyword, 14 PD-related lncRNAs were obtained from the LncRNADisease database, among which 4 lncRNAs (MALAT1, UCHL1-AS1, AK021630, and HOTAIR) were annotated to be implicated in the regulation of PD progression ( xref ); however, the murine sequences of UCHL1-AS1 and AK021630 were not available in the array."
TβRI affects UCHL1
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3
NCIT:C114489 affects UCHL1
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3
Histone_H2B affects UCHL1
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3
Delta12-PGJ2 affects UCHL1
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3
CyPG affects UCHL1
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CD45RO affects UCHL1
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3
Alzheimer Disease affects UCHL1
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sparser
"With “Parkinson’s disease” serving as the keyword, 14 PD-related lncRNAs were obtained from the LncRNADisease database, among which 4 lncRNAs (MALAT1, UCHL1-AS1, AK021630, and HOTAIR) were annotated to be implicated in the regulation of PD progression ( xref ); however, the murine sequences of UCHL1-AS1 and AK021630 were not available in the array."
3
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Tacrolimus (anhydrous) affects UCHL1
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2
Staurosporine affects UCHL1
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2
Shelterin complex affects UCHL1
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2
Prostaglandin affects UCHL1
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2
Prostaglandin J2 affects UCHL1
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2
Prostaglandin J2 inhibits UCHL1. 2 / 2
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2
Phenylmercury acetate affects UCHL1
2
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Phenylephrine affects UCHL1
1
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1
P53/MDM2/ARF affects UCHL1
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2
P-chloromercuribenzoic acid affects UCHL1
2
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Oxidopamine affects UCHL1
1
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1
MiR-1246 affects UCHL1
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2
reach
"We assumed that miR-1246 might target UBE2C, TNNT1, TRAIP, and UCHL1 during the regulation of ubiquitin mediated proteolysis, glycosaminoglycan binding, DNA metabolism, the PI3K-Akt-mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway."
Mercury dibromide affects UCHL1
2
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Lipopolysaccharide affects UCHL1
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2
Hydrolase activity affects UCHL1
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2
H-IAPP affects UCHL1
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2
EIF affects UCHL1
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2
Copper atom affects UCHL1
2
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sparser
"Whereas, its depletion contributes to aggresome and oligomer formation in the pathology of PD. xref Kabuta and associates found that ubiquitin C-terminal hydrolase L1 (UCHL1) () abnormally interacted with LAMP2, heat shock protein family A [Hsp70] member 8) (HSPA8) (heat shock protein 90 alpha family class B member 1 (HSP90AB1) (), and thereby, impaired CMA. xref Therefore aberrant interactions between UCHL1 and CMA components can contribute to PD pathogenesis."
Chloroquine affects UCHL1
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2
Cadmium dichloride affects UCHL1
2
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CPKCgamma gene knockout affects UCHL1
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2
Brefeldin A affects UCHL1
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2
Bisphenol A affects UCHL1
2
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UCHL1-AS1 affects UCHL1
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2
UCHL1 affects α-synuclein
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1
reach
"In Alzheimer’s disease (AD) transgenic mice, overexpression of UCHL1 has been shown to reduce Aβ production, inhibit neuritic plaque formation and improve memory deficits [15], while in PD, suppression of UCHL1 activity in vitro has been shown in non-transgenic neurons to increase accumulation of presynaptic α-synuclein [16]."
UCHL1 affects transcription, DNA-templated
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2
UCHL1 affects trans-aconitic acid
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2
UCHL1 affects shelterin complex
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2
UCHL1 affects protein ubiquitination
1
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1
UCHL1 affects phosphorylation
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2
UCHL1 affects phosphorylation AKT Ser473 Thr202
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2
eidos
"Here , we demonstrated similar mechanisms in NB cells that UCHL1 inhibition dramatically inhibited the phosphorylation of AKT at Ser473 and ERK1 / 2 at Thr202 / Tyr204 after RA administration , indicating that the effect of UCHL1 inhibition on RA-induced neuronal differentiation was associated with repression of AKT and ERK1 / 2 activities ."
UCHL1 affects p53/MDM2/ARF
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2
UCHL1 affects miR-922
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2
UCHL1 affects metabolic process
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2
UCHL1 affects lymph node metastatic carcinoma
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2
UCHL1 activates lymph node metastatic carcinoma. 2 / 2
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2
eidos
"Ubiquitin C-terminal hydrolase L1 promotes lymph node metastasis in small cell neuroendocrine carcinomas of the cervix Objective To screen for specific differentially expressed genes in small cell neuroendocrine carcinoma of the cervix ( SCNEC ) and to further explore their roles and mechanisms in tumor progression ."
UCHL1 affects hydrolase activity
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2
UCHL1 affects hydrogen peroxide
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1
1
UCHL1 affects growth
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2
UCHL1 affects extravasation
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2
eidos
"UCHL1 activity inhibitor antagonizes TGFbeta / SMAD signaling and inhibits breast cancer migration and extravasation In order to study the effect of UCHL1 activity inhibition on the TGFbeta pathway and breast cancer metastasis we turned to a recently reported panel of UCHL1 inhibitors and decided to synthesize and characterize one of the most potent ones ( 23 ) ."
UCHL1 affects eIF
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2
UCHL1 affects detection clinical lung adenocarcinoma
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2
sparser
"Whereas, its depletion contributes to aggresome and oligomer formation in the pathology of PD. xref Kabuta and associates found that ubiquitin C-terminal hydrolase L1 (UCHL1) () abnormally interacted with LAMP2, heat shock protein family A [Hsp70] member 8) (HSPA8) (heat shock protein 90 alpha family class B member 1 (HSP90AB1) (), and thereby, impaired CMA. xref Therefore aberrant interactions between UCHL1 and CMA components can contribute to PD pathogenesis."
UCHL1 affects breast cancer migration
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2
eidos
"UCHL1 activity inhibitor antagonizes TGFbeta / SMAD signaling and inhibits breast cancer migration and extravasation In order to study the effect of UCHL1 activity inhibition on the TGFbeta pathway and breast cancer metastasis we turned to a recently reported panel of UCHL1 inhibitors and decided to synthesize and characterize one of the most potent ones ( 23 ) ."
UCHL1 affects alpha-SMA
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2
UCHL1 affects activation
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2
UCHL1 affects Ub proteins
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2
UCHL1 affects UCHL1-HIF1 axis
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1
1
UCHL1 affects TNBC
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2
reach
"In a contrasting analysis, Liu et al. proposed that UCHL1 promotes breast cancer metastasises by deubiquitinating and stabilising TGFβR1 and SMAD2 in TNBC by maintaining the TGF-β signalling pathway [54], with UCHL1 inhibition using a cyanpyrrolidine-based covalent inhibitor 6RK73 or genetic knockdown antagonising TGF-β signalling in TNBC models."
UCHL1 affects Resistance
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2
UCHL1 affects PARK5
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2
reach
"In addition, overexpression of UCH-L1 enhanced PDGF-BB-induced phosphorylation of mTOR but not glycogen synthase kinase-3 beta (GSK-3beta) and attenuated rapamycin induced suppression of mTOR phosphorylation (XREF_FIG), indicating that a specific effect of UCH-L1 on mTOR activation is linked to the observed upregulation of p21 WAF1 and Cip1 protein expression."
reach
"Interestingly, when the terminal hairpin structure was disrupted by deleting nucleotides 68–77 of the invSINEB2 sequence from the full length AS Uchl1 (ΔSL1 mutant), SINEUP ability to up-regulate UchL1 protein levels was completely abolished proving a crucial role of SL1 in the activity."
reach
"Interestingly, when the terminal hairpin structure was disrupted by deleting nucleotides 68-77 of the invSINEB2 sequence from the full length AS Uchl1 ( SL1 mutant), SINEUP ability to up-regulate UchL1 protein levels was completely abolished proving a crucial role of SL1 in the activity."
UCHL1 affects MHC I
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2
UCHL1 affects LAMP-2A
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2
reach
"Additionally, to evade host innate immunity, Hr-HPV can inhibit PRR signaling through the induction of ubiquitin C-terminal hydrolase L1 (UCHL1) expression; UCHL1 blocks the activation of NF-kappaB and IRF3, both of which are transcription factors that induce the production of proinflammatory cytokines and chemokines XREF_BIBR."
reach
"The importance of K63 linked ubiquitination for TRAF3 dependent signaling was strengthened by the identification of several DUBs removing the K63 linked ubiquitination from TRAF3 : the deubiquitinating enzyme A (DUBA), OTUB1, as well as the ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) that is specifically subverted by high-risk human papillomaviruses to downregulate IRF3 activation and PRR responses [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
UCHL1 affects HA-Ub
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2
UCHL1 affects DNA repair
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2
UCHL1 affects Brain Injuries
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1
1
UCHL1 affects BAEC1
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1
1
UCHL1 affects Adenocarcinoma of Lung
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2
UCHL1 affects AD
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2
SINEUP affects UCHL1
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2
reach
"Interestingly, when the terminal hairpin structure was disrupted by deleting nucleotides 68–77 of the invSINEB2 sequence from the full length AS Uchl1 (ΔSL1 mutant), SINEUP ability to up-regulate UchL1 protein levels was completely abolished proving a crucial role of SL1 in the activity."
reach
"Interestingly, when the terminal hairpin structure was disrupted by deleting nucleotides 68-77 of the invSINEB2 sequence from the full length AS Uchl1 ( SL1 mutant), SINEUP ability to up-regulate UchL1 protein levels was completely abolished proving a crucial role of SL1 in the activity."
RA-9 affects UCHL1
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2
Parkinson Disease affects UCHL1
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2
PARK5 affects UCHL1
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2
LAMP-2A affects UCHL1
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2
KSHV LANA affects UCHL1
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2
IOP affects UCHL1
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2
IA LPS exposure affects UCHL1
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2
HA-Ub affects UCHL1
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2
AsUchl1 affects UCHL1
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2
Abeta 42 affects UCHL1
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2
reach
"We also found that monomers of Abeta 42, but not oligomers, inhibit the activity of Uch-L1, an abundant neuronal enzyme that mediates the proteosomal degradation; our data suggest that Uch-L1 inhibition interferes with the lysosomes as demonstrated by the decrease of cathepsin D, a marker of lysosomal activity [XREF_BIBR]."
AS Uchl RNA affects UCHL1
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2
AAV2 affects UCHL1
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2
15d-PGJ 2 affects UCHL1
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2
(E)-4-hydroxynon-2-enal affects UCHL1
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2
2
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Streptozocin affects UCHL1
1
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Resveratrol affects UCHL1
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1
Resveratrol inhibits UCHL1. 1 / 1
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1
Perfluorooctanoic acid affects UCHL1
1
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Neurotrophin affects UCHL1
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1
Doxycycline affects UCHL1
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1
Doxycycline activates UCHL1. 1 / 1
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1
Butane-2,3-dione affects UCHL1
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1
Butane-2,3-dione activates UCHL1. 1 / 1
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1
UCHL1 affects tumor cell
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1
UCHL1 affects proteasomal
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1
UCHL1 affects oxLDL uptake decrease
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1
UCHL1 affects motility metastatic HNSCC
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1
UCHL1 affects chemoresistance cancers
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1
UCHL1 affects cellular integrity CSMN
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1
eidos
"In an effort to bring a mechanistic insight for the CSMN degeneration in the absence of UCHL1 function , and to investigate whether introduction of UCHL1 would be sufficient to improve the cellular integrity of CSMN , we first knocked out UCHL1 protein selectively in the large subcerebral projection neurons ( SCPN ) in layer 5 or in SMN in the spinal cord by mating floxed UCHL1 ( UCHL1f / f ) mice with Rbp4cre or HB9cre mice respectively ."
UCHL1 affects Antigen
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1
UCHL1 affects Akt473
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1
UCHL1 affects (R)-noradrenaline
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1
UCHL1 inhibits (R)-noradrenaline. 1 / 1
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1
TAT-HA-Uch-L1 affects UCHL1
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1
Restraint Stress affects UCHL1
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1
N-methyl-D-aspartic acid affects UCHL1
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1
N-methyl-D-aspartic acid activates UCHL1. 1 / 1
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1
Dietary Fats affects UCHL1
1
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Antigen affects UCHL1
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1