IndraLab
Statements
USP14 affects Proteasome
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USP14 binds Proteasome.
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Proteasome binds USP14. 10 / 61
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"Moreover, the UBL domain is not strictly essential for binding to proteasomes as the USP domain maintains interactions with the OB ring of RPT subunits, in particular with Rpt1 [ xref , xref ], and indeed, truncated USP14 lacking its N-terminal UBL can associate with proteasomes [ xref , xref ]."
Proteasome binds USP14 and UCHL5. 4 / 4
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Proteasome binds USP14 and 26S. 3 / 3
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"As USP14 and Ubp6 has been shown to be activated 300-fold upon binding to the proteasome, participating in the stepwise removal of ubiquitin and sparing it from proteasomal degradation, and that a loss of USP14 activity results in reduced levels of free ubiquitin, we next analyzed free ubiquitin levels in CD4 + T cells during aging, to evaluate whether increased USP14 activity associated with the 26S proteasome, impacts levels of free cellular ubiquitin."
Proteasome binds USP14 and K63. 1 / 1
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USP14 inhibits Proteasome.
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USP14 inhibits Proteasome. 10 / 35
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"Given that several studies have confirmed that USP14 can inhibit the proteasome in vitro [XREF_BIBR, XREF_BIBR, XREF_BIBR] and can inhibit protein turnover in cells [XREF_BIBR] the investigation and development of novel anticancer therapy based on inhibition of proteasome deubiquitinating activity or regulation of protein turnover is indicated."
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"Because K48 linked ubiquitin chains are a robust biomarker of ubiquitin proteasome system function [XREF_BIBR], and we found no difference in the catalytic capacity of TgUsp14CA and wild type proteasomes in vitro, it is unlikely that USP14 inhibition in the nervous system causes global alterations in proteasome activity."
USP14 activates Proteasome.
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USP14 activates Proteasome. 10 / 19
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"Loss of Ubp6 function, for example, increases aneuploidy tolerance in yeast, presumably due to an elevated proteasome capacity for turning over higher protein levels, and pharmacological inhibition of Usp14 in human cells has been shown to stimulate proteasome activity XREF_BIBR - XREF_BIBR."
USP14 deubiquitinates Proteasome.
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USP14 deubiquitinates Proteasome. 2 / 2
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"Given that proteasome deubiquitination mediated by USP14 has fundamental roles in regulating proteasomal degradation of ubiquitinylated substrates XREF_BIBR XREF_BIBR, it is rational to speculate that perturbation of ubiquitin chain trimming functions of PfUSP14 may impact intraerythrocytic parasite development and cause difficulties for parasite egress from the host cell."
USP14 deubiquitinates Proteasome on S26. 2 / 2
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USP14 is modified
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USP14 is phosphorylated.
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"Interestingly, we found that USP14 was associated with RelA, a binding partner of I-κB, suggesting that RelA is the linker between USP14 and I-κB. Lipopolysaccharide (LPS) treatment induced serine phosphorylation of USP14 as well as further reducing I-κB levels in HA-USP14-overexpressed MLE12 cells as compared with empty vector transfected cells."
sparser
"1) We analyzed the distribution of phosphorylated and total USP14 by glycerol gradient centrifugation (Koulich et al., 2008) and found that phosphorylated USP14 was largely present in fractions without proteasome while unphosphorylated USP14 was found in the same fractions with proteasome ( xref )."
sparser
"Finally, USP14 S432 is dramatically more phosphorylated in PTEN knockout mouse embryonic fibroblasts (MEFs), which carry high levels of Akt activity, than that of WT MEFs as determined by western blotting using the phospho-USP14(S432) antibody and phos-tag electrophoresis ( xref ), and the phosphorylation of USP14 S432 was blocked by Akt inhibitors ( xref )."
rlimsp
"Thus, S432 phosphorylated and unphosphorylated USP14 might be distributed differently in the cells. We next determined whether phospho-mimetic mutant of USP14 could be further activated by interacting with proteasome. Interestingly, we found that the Ub-AMC hydrolytic activity of S432E mutant could be further activated when incubated with proteasome in vitro (Figure 3H). Taken together, these results suggest that S432 phosphorylation and interaction with proteasome may be two different regulatory mechanisms for USP14."
sparser
"Xu et al. reported that serine/threonine kinase could phosphorylate USP14 at Ser432, thus activating its deubiquitinating activity by transforming its catalytic site from the inactive conformation to the active form. xref Whether the activity of USP14 is regulated by serine/threonine kinase in ESCC is still questionable."
rlimsp
"The enrichment of phosphorylated peptides by TiO2 was performed with tryptic USP14 peptides. The enriched phosphorylated peptides were analyzed on Orbitrap Fusion mass spectrometer (Thermo Scientific). The activation type of HCD was performed for MS2. Protein identification was performed by Thermo Proteome discoverer (v1.4) with Sequest HT. The precursor mass tolerance was set at 10 ppm, and the fragment mass tolerance was set at 0.1 Da. The cysteine carboxyamido methylation was set as a static modification, and phosphorylated serine, threonine, and tyrosine residues were set as variable modifications."
USP14 is acetylated.
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USP14 is produced.
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Proteasome affects USP14
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Proteasome binds USP14.
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Proteasome binds USP14. 10 / 61
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"Moreover, the UBL domain is not strictly essential for binding to proteasomes as the USP domain maintains interactions with the OB ring of RPT subunits, in particular with Rpt1 [ xref , xref ], and indeed, truncated USP14 lacking its N-terminal UBL can associate with proteasomes [ xref , xref ]."
Proteasome binds USP14 and UCHL5. 4 / 4
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Proteasome binds USP14 and 26S. 3 / 3
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"As USP14 and Ubp6 has been shown to be activated 300-fold upon binding to the proteasome, participating in the stepwise removal of ubiquitin and sparing it from proteasomal degradation, and that a loss of USP14 activity results in reduced levels of free ubiquitin, we next analyzed free ubiquitin levels in CD4 + T cells during aging, to evaluate whether increased USP14 activity associated with the 26S proteasome, impacts levels of free cellular ubiquitin."
Proteasome binds USP14 and K63. 1 / 1
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Proteasome activates USP14.
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Proteasome activates USP14. 10 / 16
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"This is consistent with previous studies showing that PGJ2 lowers 26S proteasome levels and activity [XREF_BIBR, XREF_BIBR], and inhibits some of the thiol deubiquitinases including UCH-L1 and UCH-L3 [XREF_BIBR, XREF_BIBR], as well as Ub-isopeptidase activity [XREF_BIBR], but not USP14 as shown here in our current studies."
Proteasome deubiquitinates USP14.
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Proteasome deubiquitinates USP14. 10 / 15
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"Furthermore, since deubiquitinating enzymes associated with the proteasome are responsible for ubiquitin trimming from substrates targeted to the proteasome for degradation, and in light of growing evidence that the manner in which proteasome associated deubiquitinating enzymes, USP14 and UCH37, deubiquitinate substrates can in fact suppress and delay degradation and modulate proteasome function, we decided to next analyze the functional activity of the proteasome associated deubiquitinating enzyme USP14."
Proteasome inhibits USP14.
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"Comparison of the crystal structures for the free and Ub bound catalytic core domain of USP14 suggests that the enzyme is activated by conformational translocation of two enzyme surface loops, which block access of the Ub C-terminus to the active site in the free enzyme ( xref )."
sparser
"It is also a reversible non‐selective competitive inhibitor of USP14, targeting the formation of Ub‐USP14 or Ub‐UCHL5 conjugates. xref This is achieved by inhibiting the enzymatic activity of USP14 and UCHL5, and VLX1570 shows significant anti‐cancer impact in multiple myeloma and Waldenstrom's macroglobulinemia. xref Anchored in these findings, a phase 1/2 trial evaluating the efficacy and tolerability of VLX1570 in patients with relapsed or refractory multiple myeloma is currently under way (NCT02372240). xref "
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"In the USP14/ubiquitin-aldehyde complex, where the ubiquitin C terminus is covalently bound to the site cysteine and only one C-terminal oxygen is present, Asn108 (Asn218 in USP2) interacts with the hydroxyl of the thiohemiacetal, while Asn111 (Asn221 in USP2) makes no specific interactions and is rotated away from the active site."
Acetaldehyde binds Ubiquitin and USP14. 2 / 2
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"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
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"However, later work has shown that ubiquitin overexpression does not correct the ax J deficits in hippocampal short term plasticity, and that transgenic expression of a catalytically inactive form of USP14 in the nervous system mimics the neuromuscular phenotype observed in the ax J mice, but causes a only a modest reduction of free ubiquitin."
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"The degradation of Ub itself is closely related to the activities of DUBs associated with the proteasome since the loss of USP14 (or Ubp6 in yeast) or UCH37 has been shown to trigger degradation of Ub along with its target substrates, leading to depletion of the free Ub pool XREF_BIBR - XREF_BIBR."
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"By contrast, USP14 and UCHL5 are located further from the 20S core and antagonize degradation by removing Ub in a stepwise manner from the distal end, promoting substrate dissociation from the proteasome 17.The human genome encodes for approximately 90 DUBs, which fall into six classes 18, 19."
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"Toward the identification of small-molecule stimulators of the ubiquitin-proteasome system to enhance the clearance of deleterious proteins, the discovery that a proteasome associated deubiquitinating enzyme, USP14, inhibits proteasomal degradation of proteins by trimming off ubiquitin chains inspired a high-throughput screen to find inhibitors of USP14 activity [XREF_BIBR]."
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"Free Ub, but not Ub conjugate, levels were reduced in the brain of ax J mice, but neuron specific expression of the Usp14 transgene was sufficient to restore free Ub levels in the spinal cord and motor neuron axons and could rescue ataxia phenotypes with defective neuromuscular junctions in ax J mice XREF_BIBR, XREF_BIBR."
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"Analysis of spinal cord and sciatic nerve extracts from the ax J -Tg mice demonstrated that transgenic expression of Usp14 restored monomeric ubiquitin levels back to wt levels (XREF_FIG), indicating that Usp14 is required for the maintenance of monomeric ubiquitin in the spinal cord and motor neuron axons."
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"USP14 is a deubiquitinating enzyme which presents reversible association with proteasome, and can inhibit the proteasome activity via trimming K48 ubiquitin chains on the proteasome‐bound substrates.36, 37 Recent study revealed that USP14 could be phosphorylated and activated by AKT, and could negatively regulate autophagy in neurodegenerative diseases.32, 38 Herein, we validated that SPAG5‐AS1 regulated the de‐ubiquitination of SPAG5 relying on USP14, and therefore activated AKT/mTOR signalling."
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"By using overexpression model of chicken UCH-L5 and b-AP15 inhibitor of UCH-L5 and USP14 [XREF_BIBR], which inhibited UCH-L5 at low molar concentration, but it did not significantly inhibit other DUBs in HD11 cells (XREF_SUPPLEMENTARY), we observed the overexpression of UCH-L5 had a negative effect on cell viability, which depended on its catalytic activity as a DUB, since if UCH-L5 overexpressing cells were treated with b-AP15 inhibitor, the cell viability was partially restored (XREF_FIG)."
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"We also found that inhibition of USP-14 and UCHL5 activities by the ITCs caused increased levels of USP14 and UCHL5 proteins, but not the third 19S deubiquitinating enzyme (DUB), POH1 and RPN11, suggesting feedback loop activation and further supporting that ITCs are inhibitors of proteasomal cysteine DUBs."
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"We also found that inhibition of USP-14 and UCHL5 activities by the ITCs caused increased levels of USP14 and UCHL5 proteins, but not the third 19S deubiquitinating enzyme (DUB), POH1 and RPN11, suggesting feedback loop activation and further supporting that ITCs are inhibitors of proteasomal cysteine DUBs."
USP14 affects cell population proliferation
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USP14 activates cell population proliferation.
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USP14 activates cell population proliferation. 10 / 58
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"To explore the underlying mechanism by which USP14 promotes cell proliferation in LNcap cells, we monitored the cell cycle progression of each group exposed to various concentrations of IU1 (25, 50, 100muM) and found that inhibition of USP14 activity dramatically induced G0/G1 cell cycle arrest at different time points (0, 6, 12, 24, 48h) (XREF_FIG)."
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"We found that USP14 inhibition by shRNA significantly suppressed the proliferation of MDA-MB-231, MDA-MB-453, MDA-MB-468, HCC1937, and MCF7 breast cancer cell lines; however USP14 knockdown did not affect the proliferation of T47D cells, which could be related to the fact that these cells express very high levels of ER and very low levels of AR."
USP14 inhibits cell population proliferation.
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USP14 inhibits cell population proliferation. 10 / 11
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"We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells."
sparser
"We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells."
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"In addition, western blot analysis and immunofluorescent staining assay indicated that USP14 silencing significantly downregulated the abundance of AR in both the nucleus and cytoplasm under androgen stimulation, suggesting that cytosolic USP14 is not required for AR translocation and that USP14 silencing induced decrease of nuclear AR could be due to the decrease of total AR protein."
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"Treatment of control MDA-MB-453 (either scramble shRNA or parental) cells with CHX for up to 12h caused decreased levels of AR, suggesting a contribution of AR protein synthesis to endogenous AR protein levels; however, co-treatment of CHX and USP14 shRNA or IU1 resulted more rapid decrease in levels of endogenous AR protein, strongly suggest that deubiquitination of AR protein by USP14 is essential for its protein stability."
"Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G0/G1 to S phase transition and inducing apoptosis."
reach
"However, multi‐center‐based investigation is needed for further validation of its predictive value.It has been shown that silencing of USP14 could block the cell cycle progression and elicit caspase‐dependent apoptosis in MM cells.13 Also, inhibition of USP14 led to G0/G1 arrest by accelerating the ubiquitination and degradation of AR in prostate cancer cells."
reach
"We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells."
sparser
"Comparison of the crystal structures for the free and Ub bound catalytic core domain of USP14 suggests that the enzyme is activated by conformational translocation of two enzyme surface loops, which block access of the Ub C-terminus to the active site in the free enzyme ( xref )."
sparser
"It is also a reversible non‐selective competitive inhibitor of USP14, targeting the formation of Ub‐USP14 or Ub‐UCHL5 conjugates. xref This is achieved by inhibiting the enzymatic activity of USP14 and UCHL5, and VLX1570 shows significant anti‐cancer impact in multiple myeloma and Waldenstrom's macroglobulinemia. xref Anchored in these findings, a phase 1/2 trial evaluating the efficacy and tolerability of VLX1570 in patients with relapsed or refractory multiple myeloma is currently under way (NCT02372240). xref "
reach
"In the USP14/ubiquitin-aldehyde complex, where the ubiquitin C terminus is covalently bound to the site cysteine and only one C-terminal oxygen is present, Asn108 (Asn218 in USP2) interacts with the hydroxyl of the thiohemiacetal, while Asn111 (Asn221 in USP2) makes no specific interactions and is rotated away from the active site."
Acetaldehyde binds Ubiquitin and USP14. 2 / 2
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"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
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"On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate 8-10 , enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding."
sparser
"On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate 8-10 , enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding."
USP14 affects apoptotic process
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USP14 inhibits apoptotic process.
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USP14 inhibits apoptotic process. 10 / 26
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"b-AP15, a small molecule inhibitor of two 19S regulatory-particle-associated deubiquitinases, USP14 and ubiquitin C-terminal hydrolase 5, could efficiently induce cell apoptosis or cell death in colorectal cancer cell line HCT116.24 In addition, b-AP15 can suppress the growth of FaDu squamous cell carcinoma cells.25 Our stratified survival analysis indicated that high USP14 expression could distinguish poor outcomes of patients with either early (TNM stage I-II) or advanced clinical stage (TNM stage III-IV), suggesting that USP14 may play a significant role throughout the development of ESCC."
eidos
"19 In addition , small USP14 inhibitors , such as WP1130 , b-AP15 , AC17 , and pyrithione , could dramatically suppressed cell proliferation and promoted apoptosis in various malignancies.9 , 20 , 21 , 22 , 23 , 24 However , we did not observe any disturbed biological process , such as cell cycle progression , cell proliferation , and apoptosis , in USP14-deficient GC cells , although silencing of USP14 dramatically inhibited Akt and ERK signaling pathways ."
Modified USP14 inhibits apoptotic process. 1 / 1
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USP14 activates apoptotic process.
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USP14 activates apoptotic process. 10 / 16
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"Our recent study exemplifies the feasibility of such an approach : specifically, we showed that blockade of 19S associated DUBs USP14 and UCHL5 with a small-molecule inhibitor (bAP15 and VLX1570) induces apoptosis in MM cells and overcome bortezomib resistance, with a favorable toxicity profile."
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"Together, it was suggested that SPAG5‐AS1 stabilized SPAG5 protein through interacting with USP14 in HG‐treated HPCs, and that USP14 and AKT/mTOR formed a positive feedback loop.3.7
SPAG5-AS1 promoted apoptosis and attenuated autophagy in HG-treated HPCs through SPAG5/AKT/mTOR pathway."
IU1 affects USP14
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IU1 inhibits USP14.
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IU1 activates USP14.
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"To verify whether this shRNA effect is dependent on inhibition of the deubiquitinating activity of USP14, we used IU1, a potent pharmacological inhibitor that selectively inhibits USP14 by preventing its docking on the proteasome [XREF_BIBR], and tested the effect of USP14 inhibition by IU1 on the AR expression in breast cancer cells."
IU1 binds USP14.
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USP14 affects proteolysis
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USP14 inhibits proteolysis.
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USP14 inhibits proteolysis. 10 / 23
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"We also found enhanced expression of transcripts encoding two ubiquitin-specific proteases (Table 2), including USP14 that suppresses protein degradation through deubiquitination of proteasome substrates, non-catalytic inhibition of proteasome activity, and by regulating autophagy (de Poot et al. 2017; Xu et al. 2016)."
USP14 activates proteolysis.
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"In future studies, the investigation of alterations in the transduction pathway of USP14 and FASN using transcriptomic analysis is warranted to understand not only the interaction between the two proteins but also the correlation of the interactomes.Taken together, the results reveal that USP14 negatively regulates FASN levels unexpectedly in the cancer cells, and as a result, inhibition of USP14 was not conducive to cancer cell death through inhibition of FASN."
| PMC
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"Based on a previous finding that Usp14 is a novel DUB for FASN and enhances FASN stability by blocking proteasomal degradation in MPHs, we expected that a USP14 inhibitor IU1 could further reduce the activity of FASN by interfering with FASN stability when used together with a FASN inhibitor."
| PMC
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"USP14 is a regulator of de‐ubiquitination and has been reported to be activated through AKT/mTOR pathway and negatively regulate autophagy by K48 de‐ubiquitination in neurodegenerative diseases.32 Hence, we speculated that SPAG5‐AS1 might regulate SPAG5 through USP14.RNA immunoprecipitation analysis confirmed that SPAG5‐AS1 was abundant in USP14‐binding complexes (Figure 6B)."
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"Together, it was suggested that SPAG5‐AS1 stabilized SPAG5 protein through interacting with USP14 in HG‐treated HPCs, and that USP14 and AKT/mTOR formed a positive feedback loop.3.7
SPAG5-AS1 promoted apoptosis and attenuated autophagy in HG-treated HPCs through SPAG5/AKT/mTOR pathway."
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"On the other hand, it is also possible that the IU1 induced neuroprotection in the post-ischemic mouse brains is a synergistic effect of multiple pathways activated by suppression of USP14 through IU1, since recent results suggest that inhibition of USP14 by IU1 in vitro elevates autophagy activity."
sparser
"Furthermore, by multiple methods, S5 was revealed to directly bind with ubiquitin-specific proteases 14 (USP14) at Ser404, Phe405, and Cys414 by hydrogen bond to inhibit its deubiquitinating activity, and block USP14–TRAF6 (TNF receptor associated factor 6) interaction, subsequently promoting ubiquitination of Beclin1, interrupting Beclin1–Bcl2 interaction, and accumulating the autophagosome in macrophages, which finally resulted in the blockade of M1-like macrophage polarization."
sparser
"Furthermore, by multiple methods, S5 was revealed to directly bind with ubiquitin-specific proteases 14 (USP14) at Ser404, Phe405, and Cys414 by hydrogen bond to inhibit its deubiquitinating activity, and block USP14–TRAF6 (TNF receptor associated factor 6) interaction, subsequently promoting ubiquitination of Beclin1, interrupting Beclin1–Bcl2 interaction, and accumulating the autophagosome in macrophages, which finally resulted in the blockade of M1-like macrophage polarization."
B-AP15 affects USP14
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sparser
"We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells."
WP1130 affects USP14
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USP14 affects cell cycle
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USP14 activates cell cycle.
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USP14 activates cell cycle. 10 / 14
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"We confirmed that AR was highly expressed in the androgen responsive prostate cancer cells (LNcap cells) but was hardly detectable in the androgen-irresponsive prostate cancer cells (DU145 and PC3 cells) tested here (XREF_FIG), implying that the induction of cell cycle arrest by USP14 inhibition is AR dependent."
reach
"However, multi‐center‐based investigation is needed for further validation of its predictive value.It has been shown that silencing of USP14 could block the cell cycle progression and elicit caspase‐dependent apoptosis in MM cells.13 Also, inhibition of USP14 led to G0/G1 arrest by accelerating the ubiquitination and degradation of AR in prostate cancer cells."
USP14 inhibits cell cycle.
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USP14 inhibits cell cycle. 5 / 5
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"To explore the underlying mechanism by which USP14 promotes cell proliferation in LNcap cells, we monitored the cell cycle progression of each group exposed to various concentrations of IU1 (25, 50, 100muM) and found that inhibition of USP14 activity dramatically induced G0/G1 cell cycle arrest at different time points (0, 6, 12, 24, 48h) (XREF_FIG)."
reach
"In an effort to elucidate the mechanisms underlying this regulation, the Cui group showed that TLR4 stimulation activates the TRAF2/6 complex, which ubiquitinates NLRC5 on Lys1178 residue, presumably leading to its degradation and release of IKKalpha and IKKbeta to complex with IKKgamma [XREF_BIBR, XREF_BIBR] (XREF_FIG) This study also showed that the ubiquitin specific protease 14 (USP14) deubiquitinates NLRC5 to sustain the NLRC5 mediated inhibition of NF-kappaB activation."
"The researchers propose that, after the ubiquitination of NLRC5 at lysine 1178 is catalyzed by TRAF2/6, USP14 specifically removes the polyubiquitin chains from NLRC5 to enhance NLRC5-mediated inhibition of IKK–NF-κB signaling, thus forming a coherent feedforward loop to regulate IKK–NF-κB activation"
sparser
"Our previous data have also shown that TRIM14 recruits USP14 to accelerate the stabilization of cGAS in response to virus infection, xref as a pair of mutual binding partners, TRIM14‐USP14 in this context has been convinced to regulate noncanonical NF‐κB signaling through the control of selective autophagy."
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"Thus, the TRIM14‐USP14 complex promotes the activation of noncanonical NF‐κB pathway through the crosstalk with autophagy.Autophagy is an essential homeostatic process for clearance of intracellular protein aggregates, injured organelles, and invading cytoplasmic microbes.36 Recently, increasing evidence suggests the important regulatory roles of the crosstalk between autophagy and a variety of cellular responses, including immune responses and inflammation.37 For example, selective autophagy plays a pivotal role in regulating type I interferon signaling21, 38 and canonical NF‐κB signaling39 as described by our previous studies."
sparser
"In this study, we further verified the high expression levels of USP14 in GC cell lines and tissues and found that USP14 interacts with vimentin, de-ubiquitinates it, and increases its expression level in GC cells, which promotes cell aggressiveness, including the growth, migration and invasion of gastric cancer cells."
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"In this study, we further verified the high expression levels of USP14 in GC cell lines and tissues and found that USP14 interacts with vimentin, de-ubiquitinates it, and increases its expression level in GC cells, which promotes cell aggressiveness, including the growth, migration and invasion of gastric cancer cells."
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"Previous studies have shown that downregulation of USP14 leads to increased expression of E-cadherin and decreased expression of N-cadherin and vimentin in esophageal squamous cell carcinoma (ESCC) cells, as well as suppresses the migration and invasion of ESCC cells through the Wnt and beta-catenin signaling pathway."
sparser
"Our previous data have also shown that TRIM14 recruits USP14 to accelerate the stabilization of cGAS in response to virus infection, xref as a pair of mutual binding partners, TRIM14‐USP14 in this context has been convinced to regulate noncanonical NF‐κB signaling through the control of selective autophagy."
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"Thus, the TRIM14‐USP14 complex promotes the activation of noncanonical NF‐κB pathway through the crosstalk with autophagy.Autophagy is an essential homeostatic process for clearance of intracellular protein aggregates, injured organelles, and invading cytoplasmic microbes.36 Recently, increasing evidence suggests the important regulatory roles of the crosstalk between autophagy and a variety of cellular responses, including immune responses and inflammation.37 For example, selective autophagy plays a pivotal role in regulating type I interferon signaling21, 38 and canonical NF‐κB signaling39 as described by our previous studies."
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"Previous in vitro studies indicated that either loss of USP14 or inhibition of USP14’s catalytic activity increased the degradation of both model proteasome substrates and over-expressed TARDBP, PRNP, and MAPT proteins in cultured cells (Hanna et al., 2006; Homma et al., 2015; Lee et al., 2010; Lee et al., 2011)."
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"Although pharmacological inhibitors of USP14's ubiquitin-hydrolase activity reduced microtubule associate protein tau, tar DNA binding protein, and prion protein in culture, the effect was similar in wild type and USP14-deficient neurons, thus impacting their use for specifically evaluating USP14 in a therapeutic manner."
eidos
"13 IU1 , an inhibitor of USP14 , can increase UPS activities , promote Tau degradation , and enhance mitochondrial elimination in neuronal cells.14 , 15 , 16 Similarly , dysregulation of USP14 has been reported in several tumors , including breast cancer , lung adenocarcinoma , and epithelial ovarian cancer.17 , 18 , 19 However , whether USP14 is involved in preeclampsia remains elusive ."
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"However, similar to what we observed in the hippocampi (Figure 2), this genetic reduction of USP14 was not sufficient to decrease the levels of the TARDBP, PRNP, or MAPT proteins, as the steady-state levels of these proteins were similar in the cortical neurons cultured from the USP14-deficient mice and the wild type controls (Figure S3)."
VLX1570 affects USP14
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VLX1570 inhibits USP14.
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"The small molecule VLX1570 and an analog b-AP15 specifically block the activity of DUBs USP14 and UCHL5 in the 19S regulatory subunit, which results in the rapid accumulation of high molecular weight ubiquitin conjugates, proteasome shutdown, and robust anti-tumor activity in well established orthotopic and xenograft models of MM, lymphoma, Ewing 's sarcoma, and other malignancies [XREF_BIBR - XREF_BIBR]."
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"Notwithstanding this success, the potency of pimozide (IC 50 ~ 2muM) is lower than those of clinically approved UPS inhibitor 26S proteasome inhibitor Bortezomib (IC 50 ~ 100nM) (XREF_FIG and XREF_TABLE), and another UPS inhibitor VLX1570, which inhibited the DUBs UCHL5 and USP14 (IC 50 ~ 100nM) and was previously studied in clinical trials but terminated due to limiting toxicities (study identifier NCT02372240)."
VLX1570 binds USP14.
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VLX1570 activates USP14.
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"Notwithstanding this success, the potency of pimozide (IC50 ~2 μM) is lower than those of clinically approved UPS inhibitor 26S proteasome inhibitor Bortezomib (IC50 ~100 nM) (Fig. 1 and Table 2), and another UPS inhibitor VLX1570, which inhibited the DUBs UCHL5 and USP14 (IC50 ~100 nM) and was previously studied in clinical trials but terminated due to limiting toxicities (study identifier NCT02372240) (ClinicalTrials.gov, 2018; Wang et al., 2016)."
USP14 inhibits USP14.
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3
1
reach
"H/R treatment substantially enhanced the expression levels of USP14 mRNA and protein expression (Figure 3A–C), and p‐p65 protein expression (Figures 3B and 3D) in HTR8/Svneo and B6Tert‐1 cell lines.3.4
Depletion of USP14 abrogated H/R-induced upregulation of USP14, p-p65, and proinflammatory cytokines."
reach
"We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells."
USP14 activates USP14.
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2
reach
"H/R treatment substantially enhanced the expression levels of USP14 mRNA and protein expression (Figure 3A–C), and p‐p65 protein expression (Figures 3B and 3D) in HTR8/Svneo and B6Tert‐1 cell lines.3.4
Depletion of USP14 abrogated H/R-induced upregulation of USP14, p-p65, and proinflammatory cytokines."
reach
"Furthermore, we found that NCOA4 was upregulated by ubiquitin specific peptidase 14 (USP14) via a deubiquitination process in damaged neurons, and we found evidence of pharmacological inhibition of USP14 effectively reducing NCOA4 levels to protect neurons from ferritinophagy-mediated ferroptosis."
USP14 decreases the amount of USP14.
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2
USP14 increases the amount of USP14.
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1
sparser
"Consistently, silencing TRIM28 using two independent shRNAs (Supplementary Fig. xref ) failed to alter the levels of insoluble K48 polyUb conjugates (Supplementary Fig. xref ) or the USP14-PSMD2 interaction (Supplementary Fig. xref ), underscoring the specific effect of TRIM11 on the proteasome."
reach
"In this study, we aimed to clarify the role of the USP14-NLRC5 pathway in wear particle induced osteolysis in vitro and in vivo We found that NLRC5 or USP14 overexpression inhibits titanium particle induced proinflammatory tumor necrosis factor alpha (TNF-alpha) production and NF-kappaB pathway activation, and also decreases M1 macrophage polarization and PI3K and AKT pathway activation."
reach
"Importantly, we found that depletion of USP14 resulted in downregulation of TNF‐α, IL‐6, and IL‐1β mRNA expression in HTR8/Svneo and B6Tert‐1 (Figure 4B–D), suggesting that USP14 regulates TNF‐α, IL‐6, and IL‐1β expression through activation of NF‐κB activity.3.5
Inhibition of USP14 suppressed H/R-induced NF-kappaB and MAPK activation."
sparser
"Consistently, silencing TRIM28 using two independent shRNAs (Supplementary Fig. xref ) failed to alter the levels of insoluble K48 polyUb conjugates (Supplementary Fig. xref ) or the USP14-PSMD2 interaction (Supplementary Fig. xref ), underscoring the specific effect of TRIM11 on the proteasome."
sparser
"In this study, we further verified the high expression levels of USP14 in GC cell lines and tissues and found that USP14 interacts with vimentin, de-ubiquitinates it, and increases its expression level in GC cells, which promotes cell aggressiveness, including the growth, migration and invasion of gastric cancer cells."
reach
"In this study, we further verified the high expression levels of USP14 in GC cell lines and tissues and found that USP14 interacts with vimentin, de-ubiquitinates it, and increases its expression level in GC cells, which promotes cell aggressiveness, including the growth, migration and invasion of gastric cancer cells."
USP14 affects endoplasmic reticulum
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10
USP14 inhibits endoplasmic reticulum.
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4
USP14 activates endoplasmic reticulum.
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3
USP14 increases the amount of endoplasmic reticulum.
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2
USP14 ubiquitinates endoplasmic reticulum.
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1
USP14 leads to the ubiquitination of endoplasmic reticulum. 1 / 1
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1
USP14 affects cell growth
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1
8
1
USP14 activates cell growth.
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1
7
USP14 activates cell growth. 8 / 8
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1
7
reach
"As shown in XREF_FIG, USP14 inhibition or silence failed to induce apoptosis or PARP cleavage but instead induced moderate decreases of p53 and Bax, suggesting that cell growth suppression mediated by USP14 inhibition or silence is through promoting cell proliferation, independent of cell death."
reach
"Since we have observed that inhibition or knockdown of USP14 inhibited cell growth in LNcap cells, we further investigated whether USP14 inhibition or silence induces cell death of LNcap cells by measuring Annexin V-FITC and PI-positive cells with flow cytometry and by measuring PARP cleavage and p53 and Bax protein expression with western blot analyses."
USP14 inhibits cell growth.
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1
1
USP14 inhibits cell growth. 2 / 2
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1
1
sparser
"Since we have observed that inhibition or knockdown of USP14 inhibited cell growth in LNcap cells, we further investigated whether USP14 inhibition or silence induces cell death of LNcap cells by measuring Annexin V-FITC/PI-positive cells with flow cytometry and by measuring PARP cleavage and p53 and Bax protein expression with western blot analyses."
sparser
"The random RNA library contained random 40-nt sequences, flanked by a 3' region (23 bp) and a sequence containing the T7 promoter (46 bp, underlined). (C) Scheme for the SELEX strategy. (1) Purified RNAs were incubated with GST-USP14. (2) USP14-RNA complexes were captured by glutathione agarose beads. (3) Unbound RNA molecules were removed by centrifugation."
sparser
"Purified GST (data not shown), GST-USP14, GST-USP14(C114A), USP14, and USP14(C114A) were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and gels were stained with Coomassie Brilliant Blue R-250 (CBB) to determine the size and purity of proteins (Fig. 1A)."
sparser
"The random RNA library contained random 40-nt sequences, flanked by a 3’ region (23 bp) and a sequence containing the T7 promoter (46 bp, underlined). (C) Scheme for the SELEX strategy. (1) Purified RNAs were incubated with GST-USP14. (2) USP14-RNA complexes were captured by glutathione agarose beads. (3) Unbound RNA molecules were removed by centrifugation. (4) USP14-RNA complexes were dissociated with elution buffer containing excess imidazole. (5) RNAs bound to USP14 were prepared by phenol:chloroform extraction and ethanol precipitation."
sparser
"Purification of USP14 and human proteasomes, preparation of vme-proteasomes, and SELEX for USP14 aptamers. (A) Approximately 1 μ g of purified recombinant USP14, USP14(C114A), GST-USP14, and GST-USP14(C114A) was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Coomassie Brilliant Blue (CBB) staining."
reach
"Although pharmacological inhibitors of USP14's ubiquitin-hydrolase activity reduced microtubule associate protein tau, tar DNA binding protein, and prion protein in culture, the effect was similar in wild type and USP14-deficient neurons, thus impacting their use for specifically evaluating USP14 in a therapeutic manner."
reach
"However, similar to what we observed in the hippocampi (Figure 2), this genetic reduction of USP14 was not sufficient to decrease the levels of the TARDBP, PRNP, or MAPT proteins, as the steady-state levels of these proteins were similar in the cortical neurons cultured from the USP14-deficient mice and the wild type controls (Figure S3)."
reach
"Previous in vitro studies indicated that either loss of USP14 or inhibition of USP14’s catalytic activity increased the degradation of both model proteasome substrates and over-expressed TARDBP, PRNP, and MAPT proteins in cultured cells (Hanna et al., 2006; Homma et al., 2015; Lee et al., 2010; Lee et al., 2011)."
USP14 affects Neoplasm Invasiveness
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1
8
USP14 activates Neoplasm Invasiveness.
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1
5
USP14 inhibits Neoplasm Invasiveness.
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3
reach
"Our current study showed that IU1, a pharmacological deubiquitinating enzyme USP14 selective inhibitor, dramatically decreased MDM2 level, blocked G0/G1 to S phase transition, decreased cell growth and triggered cell apoptosis in cervical cancer cells, suggesting that targeting USP14 and MDM2 axis could be a potential strategy for cervical cancer therapy."
USP14 affects Cell Survival
|
1
8
USP14 inhibits Cell Survival.
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1
4
USP14 activates Cell Survival.
|
4
CD36 binds USP14.
|
7
Lipopolysaccharide affects USP14
|
7
Lipopolysaccharide activates USP14.
|
4
Lipopolysaccharide phosphorylates USP14.
|
3
USP14 affects tumor growth
|
5
reach
"Treatment with b-AP15, a UCHL5 and USP14 deubiquitinating activity inhibitor in 19S regulatory subunit, induces tumor regression and prolong the survival period of tumor-loaded mice through down-regulation of COPS5 and its downstream AP-1 and E2F1, and up-regulation of the cell cycle-related proteins p27 and Cyclin E1."
USP14 affects Neoplasm Metastasis
|
6
USP14 activates Neoplasm Metastasis.
|
4
USP14 inhibits Neoplasm Metastasis.
|
2
reach
"Collectively, these data demonstrated that USP14 promoted HCC proliferation and tumor growth.To further verify whether ablation of USP14 or/and a selective deubiquitination activity inhibitor of USP14 (IU1) could restrain HCC growth in animals, we implanted subcutaneously USP14-depleted HCCLM3 cells stably expressing USP14-specific shRNA (shUSP14) or control shRNA (shCtrl) and monitored tumor growth as they were treated with IU1 or vehicle (Figure S4A, B)."
USP14 affects CD36
|
7
reach
"19 In addition, small USP14 inhibitors, such as WP1130, b‐AP15, AC17, and pyrithione, could dramatically suppressed cell proliferation and promoted apoptosis in various malignancies.9, 20, 21, 22, 23, 24 However, we did not observe any disturbed biological process, such as cell cycle progression, cell proliferation, and apoptosis, in USP14‐deficient GC cells, although silencing of USP14 dramatically inhibited Akt and ERK signaling pathways."
reach
"Co‐IP assay demonstrated that in HG‐treated HPCs, SPAG5 was enriched in the precipitated products of anti‐USP14, and silencing SPAG5‐AS1 reduced such enrichment, with the input level of SPAG5 reduced and input level of USP14 unchanged (Figure 6D), indicating that SPAG5‐AS1 mediated the binding of USP14 to SPAG5."
sparser
"Co‐IP assay demonstrated that in HG‐treated HPCs, SPAG5 was enriched in the precipitated products of anti‐USP14, and silencing SPAG5‐AS1 reduced such enrichment, with the input level of SPAG5 reduced and input level of USP14 unchanged (Figure xref D), indicating that SPAG5‐AS1 mediated the binding of USP14 to SPAG5."
reach
"We found that the remaining active forms of both UCHL5 and USP14 (i.e., those can be covalently bound by HA-UbVS) were clearly reduced in the 26S proteasomes pre-treated with Aur at 2 muM and became completely undetectable in those pre-treated with 40 muM Aur, indicating that Aur inhibits both UCHL5 and USP14."
reach
"Here we report that (i) Aur shows proteasome-inhibitory effect that is comparable to that of bortezomib and Velcade (Vel); (ii) different from bortezomib, Aur inhibits proteasome associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; (iii) inhibition of the proteasome associated DUBs is required for Aur induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia patients."
sparser
"We found that the remaining active forms of both UCHL5 and USP14
(i.e., those can be covalently bound by HA-UbVS) were clearly reduced in the 26S
proteasomes pre-treated with Aur at 2 μM and became completely undetectable in
those pre-treated with 40 μM Aur (Fig. xref ), indicating that Aur inhibits both UCHL5 and USP14."
sparser
"Here we report that
(i) Aur shows proteasome-inhibitory effect that is comparable to that of
bortezomib/Velcade (Vel); (ii) different from bortezomib, Aur inhibits
proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S
proteasome; (iii) inhibition of the proteasome-associated DUBs is required for
Aur-induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in
vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia
patients."
USP14 affects degradation
|
6
sparser
"We further detected the change of MDM2-AR interaction using co-immunoprecipitation (co-IP), and found that USP14 inhibition or silence increased the binding of MDM2 to AR ( xref ), suggesting that USP14 inhibits the degradation of AR by decreasing the expression and phosphorylation of MDM2."
USP14 affects RP
|
6
reach
"However, similar to what we observed in the hippocampi (Figure 2), this genetic reduction of USP14 was not sufficient to decrease the levels of the TARDBP, PRNP, or MAPT proteins, as the steady-state levels of these proteins were similar in the cortical neurons cultured from the USP14-deficient mice and the wild type controls (Figure S3)."
USP14 affects HIF1-α
|
6
reach
"In line with our result, genetic or pharmacological inhibition of USP14 led to reduced phosphorylation of Akt and/or Erk1/2 in hepatocellular carcinoma cells and monocytic leukemia cells.25, 26 Moreover, inhibition of PI3K/AKT and ERK1/2 signaling pathways could enhance cisplatin sensitivity in urothelial bladder cancer cells and ovarian cancer cells, respectively.27, 28
As one of three proteasome‐associated DUBs, USP14 plays a key regulatory role in protein proteasomal degradation.29 Inhibition of USP14 activity would lead to a dysfunctional proteasome, eliciting a broad accumulation of ubiquitinated proteins."
reach
"Inhibition or knockdown of USP14 significantly augmented the ubiquitination of cyclin B1 and arrested the cell cycle at the G2/M phase, thereby inhibiting the proliferation and migration of breast cancer cells, and offering the theoretical basis for the development of USP14-targeted anticancer drugs (Table 2) (Liu et al., 2019)."
USP14 affects AR-V7
|
6
USP14 inhibits AR-V7.
|
2
USP14 decreases the amount of AR-V7.
|
2
USP14 binds AR-V7.
|
2
reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."
USP14 affects 2,5-diphenylfuran
|
6
USP14 activates 2,5-diphenylfuran.
|
4
USP14 inhibits 2,5-diphenylfuran.
|
2
UCHL5 affects RP
|
6
RP affects USP14
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6
Foci affects USP14
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5
reach
"Auranofin (Aur) inhibits proteasome associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; inhibition of the proteasome associated DUBs is required for Aur induced cytotoxicity; and Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from patients with acute myeloid leukemia [XREF_BIBR]."
Acetaldehyde affects USP14
|
5
USP14 affects ubiquitination
|
3
reach
"Superimposition of the queuine bound Tgt (Cys158Val) structure with the structure of Tgt in complex with RNA XREF_BIBR reveals that in the present conformation the dihydroxy-cyclopentenyl moiety of queuine sterically interferes with the ribose of the uracil 33 nucleotide and the phosphate at position 34."
reach
"Accordingly, this unexpected restriction did not allow us to figure out whether " wild type " Tgt, Tgt (Cys158Val) and Tgt (Val233Gly) were indeed able to accept queuine as a substrate nor did it allow us to determine Michaelis-Menten parameters as an indicator for affinity and catalytic activity."
USP14 affects prion protein
|
5
USP14 activates prion protein. 5 / 5
|
5
reach
"Although pharmacological inhibitors of USP14's ubiquitin-hydrolase activity reduced microtubule associate protein tau, tar DNA binding protein, and prion protein in culture, the effect was similar in wild type and USP14-deficient neurons, thus impacting their use for specifically evaluating USP14 in a therapeutic manner."
USP14 affects foci
|
5
USP14 affects cell migration
|
4
USP14 activates cell migration.
|
2
USP14 inhibits cell migration.
|
2
USP14 affects b-AP15
|
5
USP14 affects acetaldehyde
|
5
USP14 affects IU1
|
4
1
reach
"Superimposition of the queuine bound Tgt (Cys158Val) structure with the structure of Tgt in complex with RNA XREF_BIBR reveals that in the present conformation the dihydroxy-cyclopentenyl moiety of queuine sterically interferes with the ribose of the uracil 33 nucleotide and the phosphate at position 34."
USP14 affects mono(2-ethylhexyl) phthalate
|
4
USP14 inhibits mono(2-ethylhexyl) phthalate.
|
2
USP14 activates mono(2-ethylhexyl) phthalate.
|
2
USP14 activates mono(2-ethylhexyl) phthalate. 2 / 2
|
2
USP14 affects cell death
|
1
3
USP14 inhibits cell death. 4 / 4
|
1
3
reach
"b-AP15, a small molecule inhibitor of two 19S regulatory-particle-associated deubiquitinases, USP14 and ubiquitin C-terminal hydrolase 5, could efficiently induce cell apoptosis or cell death in colorectal cancer cell line HCT116.24 In addition, b-AP15 can suppress the growth of FaDu squamous cell carcinoma cells.25 Our stratified survival analysis indicated that high USP14 expression could distinguish poor outcomes of patients with either early (TNM stage I-II) or advanced clinical stage (TNM stage III-IV), suggesting that USP14 may play a significant role throughout the development of ESCC."
reach
"As shown in XREF_FIG, USP14 inhibition or silence failed to induce apoptosis or PARP cleavage but instead induced moderate decreases of p53 and Bax, suggesting that cell growth suppression mediated by USP14 inhibition or silence is through promoting cell proliferation, independent of cell death."
USP14 affects GC
|
4
USP14 affects ER
|
4
reach
"To further investigate whether the ESIs previously reported effect on protein translocation contributed to its inhibitory effect on IL-1 release or whether it was due to an inhibition of DUBs, we investigated the effects of a selective DUB inhibitor b-AP15 and of the protein translocation inhibitor cpd A. b-AP15 is a small molecule DUB inhibitor of the proteasome associated DUBs UCH37 and USP14, whereas cpd A is a selective inhibitor of the ER translocon with no effect on DUB activity."
UCHL5 affects Proteasome
|
4
SERPB12 affects USP14
|
4
Proteasome affects UCHL5, and USP14
|
4
Pyrithione affects USP14
|
2
1
Pyrithione activates USP14.
|
2
Pyrithione inhibits USP14.
|
1
Pyrithione inhibits USP14. 1 / 1
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1
sparser
"And only recently we have definitely confirmed that nickel pyrithione (NiPT) inhibits the 19S proteasome-associated deubiquitinases (DUBs) USP14 and UCHL5, but not the 20S proteasome peptidases, and the inhibition of proteasome-associated DUBs induces NiPT-mediated cytotoxicity, revealing a novel mechanism for the anti-cancer effects of nickel-containing compounds [ xref ]."
Pirinixic acid affects USP14
3
|
Hsa-miR-6774-5p affects USP14
3
|
Hsa-miR-6741-5p affects USP14
3
|
Hsa-miR-6736-5p affects USP14
3
|
Hsa-miR-635 affects USP14
3
|
Hsa-miR-548an affects USP14
3
|
Hsa-miR-4701-3p affects USP14
3
|
Hsa-miR-451b affects USP14
3
|
Hsa-miR-3662 affects USP14
3
|
Hsa-miR-140-3p affects USP14
3
|
Hsa-miR-1262 affects USP14
3
|
Endoplasmic reticulum affects USP14
|
3
Endoplasmic reticulum activates USP14. 3 / 3
|
3
reach
"Mechanistically, sustained ER stress up-regulated the deubiquitinating enzyme ubiquitin specific peptidase 14 (USP14), which increased the stability and levels of 3 ',5 '-cyclic monophosphate responsive element binding (CREB) protein (CBP) to enhance glucagon action and hepatic gluconeogenesis."
Cobalt dichloride affects USP14
3
|
sparser
"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
sparser
"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."
reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."
reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
sparser
"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
USP14 affects transcription, DNA-templated
|
3
USP14 affects migration
|
3
USP14 affects gamma-aminobutyric acid
|
3
USP14 increases the amount of gamma-aminobutyric acid.
|
2
USP14 increases the amount of gamma-aminobutyric acid. 2 / 2
|
2
reach
"Colocalization experiments and in vitro binding studies further indicated that USP14 and GABA A receptors are found together at synapses, that the C-terminus of USP14 can interact with the alpha1 loop of the GABA A receptor, and that expression of a GABA receptor peptide that binds USP14 can promote expression of surface GABA A receptors in HEK cells [XREF_BIBR]."
reach
"Intriguingly, Usp14 binds the alpha1 GABA A receptor subunit, and ax J mice lacking Usp14 exhibit increased GABA A receptor levels at Purkinje cell-surface membranes and increased inhibitory postsynaptic currents (IPSCs), which suggest that ubiquitin dependent GABA A receptor turnover at cerebellar synapses contributes to behavioral impairment."
USP14 inhibits gamma-aminobutyric acid.
|
1
USP14 inhibits gamma-aminobutyric acid. 1 / 1
|
1
reach
"Together, these data demonstrate physical interaction of GABA A R alpha1 and the ubiquitin specific protease Usp14, and suggest that the observed GABA A R redistribution in ataxia mice (XREF_FIG and XREF_FIG) is directly caused by the loss of Usp14, thereby indicating that GABA A R turnover is ubiquitin dependent."
USP14 affects cytokine production
|
3
USP14 affects autophagy macrophages
|
3
sparser
"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."
reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."
reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
sparser
"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
sparser
"Then multiple changes occur: this basal inhibition is reversed, more cytosolic Usp14 and Ube3c associate with the 26S particle, and the interaction of the Ub chain with Usp14 (or Uch37) activates the particle's ATPase and proteolytic capacity, all of which favor the selective and efficient degradation of ubiquitylated proteins ( xref )."
sparser
"For instance, ubiquitinated but not non-ubiquitinated proteins were shown to stimulate association of 26S proteasomes with Usp14 and Ube3c, which in the presence of attached ubiquitin-conjugates induce conformational changes of the proteasome, increase its activity and processivity ( xref ; xref ; xref ; xref )."
USP14 affects NCIT:C17764
|
3
USP14 affects Interferon
|
3
eidos
"13 IU1 , an inhibitor of USP14 , can increase UPS activities , promote Tau degradation , and enhance mitochondrial elimination in neuronal cells.14 , 15 , 16 Similarly , dysregulation of USP14 has been reported in several tumors , including breast cancer , lung adenocarcinoma , and epithelial ovarian cancer.17 , 18 , 19 However , whether USP14 is involved in preeclampsia remains elusive ."
USP14 affects ERAD
|
3
reach
"Hence, the USP14-induced enhancement in PC development through the stabilization of AR validated its potential role in PC therapy.Furthermore, USP14 was found to upregulate the abundance and transcriptional activity of activating transcription factor 2 (ATF2), which function as both a transcription factor and oncogene in PC, via its deubiquitination (Ma et al., 2018), thus enhancing the proliferation of PC cells."
USP14 affects 26S
|
3
Proteasome binds USP14 and 26S. 3 / 3
|
3
reach
"As USP14 and Ubp6 has been shown to be activated 300-fold upon binding to the proteasome, participating in the stepwise removal of ubiquitin and sparing it from proteasomal degradation, and that a loss of USP14 activity results in reduced levels of free ubiquitin, we next analyzed free ubiquitin levels in CD4 + T cells during aging, to evaluate whether increased USP14 activity associated with the 26S proteasome, impacts levels of free cellular ubiquitin."
sparser
"Then multiple changes occur: this basal inhibition is reversed, more cytosolic Usp14 and Ube3c associate with the 26S particle, and the interaction of the Ub chain with Usp14 (or Uch37) activates the particle's ATPase and proteolytic capacity, all of which favor the selective and efficient degradation of ubiquitylated proteins ( xref )."
sparser
"For instance, ubiquitinated but not non-ubiquitinated proteins were shown to stimulate association of 26S proteasomes with Usp14 and Ube3c, which in the presence of attached ubiquitin-conjugates induce conformational changes of the proteasome, increase its activity and processivity ( xref ; xref ; xref ; xref )."
Proteasome affects 26S
|
3
Proteasome binds USP14 and 26S. 3 / 3
|
3
reach
"As USP14 and Ubp6 has been shown to be activated 300-fold upon binding to the proteasome, participating in the stepwise removal of ubiquitin and sparing it from proteasomal degradation, and that a loss of USP14 activity results in reduced levels of free ubiquitin, we next analyzed free ubiquitin levels in CD4 + T cells during aging, to evaluate whether increased USP14 activity associated with the 26S proteasome, impacts levels of free cellular ubiquitin."
NCIT:C17764 affects USP14
|
3
26S affects USP14
|
3
Proteasome binds USP14 and 26S. 3 / 3
|
3
reach
"As USP14 and Ubp6 has been shown to be activated 300-fold upon binding to the proteasome, participating in the stepwise removal of ubiquitin and sparing it from proteasomal degradation, and that a loss of USP14 activity results in reduced levels of free ubiquitin, we next analyzed free ubiquitin levels in CD4 + T cells during aging, to evaluate whether increased USP14 activity associated with the 26S proteasome, impacts levels of free cellular ubiquitin."
Α1 affects USP14
|
2
Valproic acid affects USP14
2
|
Sodium dichromate affects USP14
2
|
Hsa-miR-4782-3p affects USP14
2
|
Hsa-miR-3714 affects USP14
2
|
Docking proteasome affects USP14
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2
Cadmium dichloride affects USP14
2
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Bortezomib affects USP14
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2
Bortezomib inhibits USP14. 2 / 2
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2
reach
"Notwithstanding this success, the potency of pimozide (IC 50 ~ 2muM) is lower than those of clinically approved UPS inhibitor 26S proteasome inhibitor Bortezomib (IC 50 ~ 100nM) (XREF_FIG and XREF_TABLE), and another UPS inhibitor VLX1570, which inhibited the DUBs UCHL5 and USP14 (IC 50 ~ 100nM) and was previously studied in clinical trials but terminated due to limiting toxicities (study identifier NCT02372240)."
reach
"Notwithstanding this success, the potency of pimozide (IC50 ~2 μM) is lower than those of clinically approved UPS inhibitor 26S proteasome inhibitor Bortezomib (IC50 ~100 nM) (Fig. 1 and Table 2), and another UPS inhibitor VLX1570, which inhibited the DUBs UCHL5 and USP14 (IC50 ~100 nM) and was previously studied in clinical trials but terminated due to limiting toxicities (study identifier NCT02372240) (ClinicalTrials.gov, 2018; Wang et al., 2016)."
Bis(2-ethylhexyl) phthalate affects USP14
2
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Benzo[a]pyrene affects USP14
2
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reach
"In the USP14/ubiquitin-aldehyde complex, where the ubiquitin C terminus is covalently bound to the site cysteine and only one C-terminal oxygen is present, Asn108 (Asn218 in USP2) interacts with the hydroxyl of the thiohemiacetal, while Asn111 (Asn221 in USP2) makes no specific interactions and is rotated away from the active site."
Acetaldehyde affects Ubiquitin
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2
reach
"In the USP14/ubiquitin-aldehyde complex, where the ubiquitin C terminus is covalently bound to the site cysteine and only one C-terminal oxygen is present, Asn108 (Asn218 in USP2) interacts with the hydroxyl of the thiohemiacetal, while Asn111 (Asn221 in USP2) makes no specific interactions and is rotated away from the active site."
Ubiquitin affects acetaldehyde
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2
USP14-3 affects USP14
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2
USP14 affects α1
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2
USP14 affects viral RNA genome replication
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2
USP14 activates viral RNA genome replication. 2 / 2
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2
USP14 affects tube formation
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2
USP14 affects signal transduction
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2
USP14 affects pyroptosis
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2
USP14 affects protein beta-catenin cyclin D1 c-Myc ESCC cells
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2
USP14 affects pathogenic aggregates Tau protein Alzheimer disease TDP-43
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2
eidos
"Usp14 inhibitors are able to increase the degradation rate of the pathogenic aggregates of Tau protein ( Alzheimer 's disease ) as well as TDP-43 ( amyotrophic lateral sclerosis ) , opening new exciting therapeutic approaches.3 Finally , a new set of drugs , called degraders ,16 which have the ability to trigger selective degradation of target proteins via UPS-recruiting E3 ligases , represent an invaluable strategy for basic research , as well as drug discovery and development of new therapies ."
USP14 affects lipopolysaccharide
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1
1
USP14 affects invasion ESCC cells
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2
eidos
"Downregulation of USP14 Suppresses the Activation of Wnt / beta-Catenin Signaling Pathway in ESCC Cells To investigate the molecular mechanism by which USP14 promoted proliferation and invasion in ESCC cells , we examined the effects of USP14 on the activation of the Wnt / beta-catenin signaling pathway ."
USP14 affects inflammatory response
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1
1
USP14 activates inflammatory response. 2 / 2
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1
1
reach
"On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate 8-10 , enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding."
USP14 affects function
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2
USP14 affects cell growth migration invasion cancer
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2
reach
"In the USP14/ubiquitin-aldehyde complex, where the ubiquitin C terminus is covalently bound to the site cysteine and only one C-terminal oxygen is present, Asn108 (Asn218 in USP2) interacts with the hydroxyl of the thiohemiacetal, while Asn111 (Asn221 in USP2) makes no specific interactions and is rotated away from the active site."
USP14 affects VLX1570
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2
USP14 affects Ubiquitination
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2
reach
"In the USP14/ubiquitin-aldehyde complex, where the ubiquitin C terminus is covalently bound to the site cysteine and only one C-terminal oxygen is present, Asn108 (Asn218 in USP2) interacts with the hydroxyl of the thiohemiacetal, while Asn111 (Asn221 in USP2) makes no specific interactions and is rotated away from the active site."
USP14 affects Ubiquitin, and acetaldehyde
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2
sparser
"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
reach
"They further demonstrated that inhibition of USP14 not only promoted the degradation of classic substrates of the UPP, but also promoted the clearance oxidized proteins and enhanced the resistance to oxidative stress [XREF_BIBR], indicating that the UPP is involved in targeting oxidized proteins for degradation."
reach
"They further demonstrated that inhibition of USP14 not only promoted the degradation of classic substrates of the UPP, but also promoted the clearance oxidized proteins and enhanced the resistance to oxidative stress [XREF_BIBR], indicating that ubiquitination is involved in targeting oxidized proteins for degradation."
reach
"H/R treatment substantially enhanced the expression levels of USP14 mRNA and protein expression (Figure 3A–C), and p‐p65 protein expression (Figures 3B and 3D) in HTR8/Svneo and B6Tert‐1 cell lines.3.4
Depletion of USP14 abrogated H/R-induced upregulation of USP14, p-p65, and proinflammatory cytokines."
reach
"H/R treatment substantially enhanced the expression levels of USP14 mRNA and protein expression (Figure 3A–C), and p‐p65 protein expression (Figures 3B and 3D) in HTR8/Svneo and B6Tert‐1 cell lines.3.4
Depletion of USP14 abrogated H/R-induced upregulation of USP14, p-p65, and proinflammatory cytokines."
USP14 affects UBL
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2
reach
"Co‐IP assay demonstrated that in HG‐treated HPCs, SPAG5 was enriched in the precipitated products of anti‐USP14, and silencing SPAG5‐AS1 reduced such enrichment, with the input level of SPAG5 reduced and input level of USP14 unchanged (Figure 6D), indicating that SPAG5‐AS1 mediated the binding of USP14 to SPAG5."
sparser
"Co‐IP assay demonstrated that in HG‐treated HPCs, SPAG5 was enriched in the precipitated products of anti‐USP14, and silencing SPAG5‐AS1 reduced such enrichment, with the input level of SPAG5 reduced and input level of USP14 unchanged (Figure xref D), indicating that SPAG5‐AS1 mediated the binding of USP14 to SPAG5."
sparser
"Interestingly, we found that USP14 was associated with RelA, a binding partner of I-κB, suggesting that RelA is the linker between USP14 and I-κB. Lipopolysaccharide (LPS) treatment induced serine phosphorylation of USP14 as well as further reducing I-κB levels in HA-USP14-overexpressed MLE12 cells as compared with empty vector transfected cells."
USP14 affects Q modification
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2
USP14 affects Prostatic Neoplasms
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2
reach
"In addition, USP14 was observed to upregulate the Wnt/β-catenin signaling mediated by cleaving K63-linked polyubiquitin chains (Table 2, Figure 6) (Jung et al., 2013) (Huang et al., 2015), and promote the proliferation and metastasis of HCC cells by deubiquitinating and activating PI3K (Table 2) (Wright et al., 2019; Zhang Y. et al., 2020)."
USP14 affects NHK
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2
USP14 affects KN
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2
USP14 affects K48-
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2
reach
"In the present study, we provided the evidence that both K48- and K63-linked polyubiquitination on HIF1-α were significantly reduced by overexpression of USP14, suggesting that USP14 is involved in the maintenance of HIF1-α stability by triggering K48- and K63-linked deubiquitination on HIF1-α via its deubiquitination activity."
sparser
"As further evidence for a physiological role of the interaction of USP14 with ISG15, we investigated whether the allosteric activation of USP14 also influences its reactivity toward ISG15VS. We examined labeling of USP14 with the ubiquitin- and the ISG15-based probes as a function of the concentration of added purified proteasomes."
USP14 affects I-kappaB
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2
USP14 affects G 0
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2
USP14 affects ESCC cell
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2
reach
"However, multi‐center‐based investigation is needed for further validation of its predictive value.It has been shown that silencing of USP14 could block the cell cycle progression and elicit caspase‐dependent apoptosis in MM cells.13 Also, inhibition of USP14 led to G0/G1 arrest by accelerating the ubiquitination and degradation of AR in prostate cancer cells."
USP14 affects Carcinogenesis
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2
USP14 affects CLP-induced sepsis
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2
USP14 affects BL2
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2
reach
"A series of studies have demonstrated that Ubp6 and USP14 enhances the ATPase activity of proteasome and opens the 20S gate upon treatment with ubiquitin, ubiquitin protein conjugate or active site directed probes, such as ubiquitin aldehyde (Ubal) or ubiquitin vinyl sulfone (UbVS) (XREF_FIG A, right bottom panel) [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
USP14 affects AR-FL
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2
reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."
UPS inhibitor affects USP14
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2
reach
"Notwithstanding this success, the potency of pimozide (IC 50~2 μM) is lower than those of clinically approved UPS inhibitor 26S proteasome inhibitor Bortezomib (IC 50~1 00 nM) ( Fig. 1 and Table 2 ), and another UPS inhibitor VLX1570, which inhibited the DUBs UCHL5 and USP14 (IC 50~1 00 nM) and was previously studied in clinical trials but terminated due to limiting toxicities (study identifier NCT02372240) (ClinicalTrials.gov, 2018; Wang et al., 2016) ."
reach
"Notwithstanding this success, the potency of pimozide (IC 50 ~ 2muM) is lower than those of clinically approved UPS inhibitor 26S proteasome inhibitor Bortezomib (IC 50 ~ 100nM) (XREF_FIG and XREF_TABLE), and another UPS inhibitor VLX1570, which inhibited the DUBs UCHL5 and USP14 (IC 50 ~ 100nM) and was previously studied in clinical trials but terminated due to limiting toxicities (study identifier NCT02372240)."
UBL affects USP14
|
2
sparser
"Interestingly, we found that USP14 was associated with RelA, a binding partner of I-κB, suggesting that RelA is the linker between USP14 and I-κB. Lipopolysaccharide (LPS) treatment induced serine phosphorylation of USP14 as well as further reducing I-κB levels in HA-USP14-overexpressed MLE12 cells as compared with empty vector transfected cells."
KN affects USP14
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2
IU1-47 affects USP14
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1
1
sparser
"As further evidence for a physiological role of the interaction of USP14 with ISG15, we investigated whether the allosteric activation of USP14 also influences its reactivity toward ISG15VS. We examined labeling of USP14 with the ubiquitin- and the ISG15-based probes as a function of the concentration of added purified proteasomes."
Deubiquitinase affects USP14
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2
BL2 affects rplA
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2
AR-V7 affects USP14
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2
reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."
AR-FL affects USP14
|
2
reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."
Μ affects USP14
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1
Thallium monochloride affects USP14
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1
Thallium monochloride binds USP14. 1 / 1
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1
Tetramethylrhodamine affects USP14
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1
Tetramethylrhodamine binds USP14. 1 / 1
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1
Sustained ER stress affects USP14
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1
Schizandrin B affects USP14
1
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Radio OR calculated affects USP14
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1
Proteolysis affects USP14
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1
Proteolysis activates USP14. 1 / 1
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1
Poly-Ub chains affects USP14
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1
Phenobarbital affects USP14
1
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Novel USP14-binding RNA aptamers affects USP14
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1
MiR-520a-3p affects USP14
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1
MiR-326 affects USP14
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1
MiR-320a affects USP14
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1
Leflunomide affects USP14
1
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Hsa-miR-6787-3p affects USP14
1
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Hsa-miR-6738-3p affects USP14
1
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Holoenzyme affects USP14
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1
HQTRT1 affects USP14
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1
Copper(II) sulfate affects USP14
1
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Bacterial RNAP apoenzyme affects USP14
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1
BAP15 affects USP14
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1
Ax J mutation affects USP14
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1
Alpha-subunit affects USP14
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1
reach
"AML-1 belongs to the CBF family of transcription factors, whose members are heterodimers consisting of a alpha-subunit (CBF alpha), which binds to the DNA consensus sequence TGT and CGGT, and a beta-subunit (CBF beta) that enhances the DNA binding affinity through alpha-subunit rather than binding to DNA directly [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
XKB affects USP14
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1
VLX 1570 affects USP14
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1
UbVS affects USP14
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1
USP14 affects ubiquitinated
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1
USP14 affects ubiquitin-protein conjugates
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1
USP14 affects turnover
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1
USP14 affects tumorigenicity mice
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1
USP14 affects thallium monochloride
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1
Thallium monochloride binds USP14. 1 / 1
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1
USP14 affects tetramethylrhodamine
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1
Tetramethylrhodamine binds USP14. 1 / 1
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1
USP14 affects tau-and paraquat-induced cytotoxicity
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1
USP14 affects rescue substrates
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1
USP14 affects proteasome substrates
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1
eidos
"We also tested the effect of USP14 inhibition on proteome stability using the specific inhibitor IU1-47 ( Boselli et al ., 2017 ) alone or in combination with XL-188 , since USP14 inactivation promotes degradation of some proteasome substrates in vitro and in human cells ( Lee et al ., 2010 ) ."
USP14 affects proteasome protein turnover cells9
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1
USP14 affects proteasome function
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1
USP14 affects prostaglandin J2
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1
USP14 inhibits prostaglandin J2. 1 / 1
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1
USP14 affects preQ 0
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1
USP14 affects poly-Ub chains
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1
USP14 affects p-Akt T308 S473 p-ERK T202 Y204 MKN45 KATO cells
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1
USP14 affects migration EC109 Fig. 3A TE10 cells
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1
USP14 affects miR-520a-3p
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1
USP14 affects melanoma cells independent mutational cell
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1
USP14 affects inflammatory responses trophoblast cells
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1
eidos
"Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK / NF-kappaB signaling INHIBITING USP14 AMELIORATES INFLAMMATORY RESPONSE ZHAO and ZONG Abstract Background Preeclampsia can cause severe consequences for pregnant women and infants , and developing effective medicine or methods to prevent or treat patients with preeclampsia is urgently needed ."
USP14 affects holoenzyme
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1
USP14 affects hQTRT1
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1
USP14 affects enzalutamide
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1
USP14 inhibits enzalutamide. 1 / 1
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1
USP14 affects elucidated421
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1
USP14 affects deubiquitination Beclin1
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1
USP14 affects cisplatin resistance
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1
USP14 affects cell cycle arrest
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1
USP14 activates cell cycle arrest. 1 / 1
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1
USP14 affects cell anchorage-independence growth NB cells
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1
USP14 affects breast cancer cell
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1
USP14 affects beta-MHC
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1
USP14 affects base
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1
USP14 affects bacterial RNAP apoenzyme
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1
USP14 affects autophagy flux
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1
USP14 affects autophagy ER stress-mediated A549 cells
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1
USP14 affects apoptotic population flow cytometry
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1
USP14 affects alpha-subunit
|
1
reach
"AML-1 belongs to the CBF family of transcription factors, whose members are heterodimers consisting of a alpha-subunit (CBF alpha), which binds to the DNA consensus sequence TGT and CGGT, and a beta-subunit (CBF beta) that enhances the DNA binding affinity through alpha-subunit rather than binding to DNA directly [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
USP14 affects accumulation ubiquitinated proteins
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1
USP14 affects WP1130
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1
USP14 affects UbVS
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1
USP14 affects TGT CGT
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1
reach
"Then qPCR analyses were performed with QuFast SYBR Green PCR Master Mix (EQ001; ELK Biotechnology, Wuhan, China) and the following gene specific primers (44), forward 5′-AGG CAG TGT CTT AGC TGG TTG T-3′, reverse 5′-CTC AAC TGG TGT CGT GGA GTC-3′ for miR-34a-5p, and forward 5′-CTC GCT TCG GCA GCA CAT-3′, reverse 5′-AAC GCT TCA CGA ATT TGC GT-3′ for U6, on a StepOne™ Real-Time PCR system (Life technologies, Carlsbad, CA, USA)."
USP14 affects SV
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1
USP14 affects RUNX-CBFbeta heterodimers
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1
USP14 affects RIG-I-triggered NF-kappaB activation
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1
USP14 affects PCAT6
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1
USP14 affects OSCC
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1
USP14 affects Multiple Myeloma
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1
USP14 inhibits Multiple Myeloma. 1 / 1
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1
USP14 affects K63-
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1
USP14 affects K63
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1
Proteasome binds USP14 and K63. 1 / 1
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1
USP14 affects Ischemic Stroke
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1
USP14 activates Ischemic Stroke. 1 / 1
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1
USP14 affects IkappaB protein
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1
USP14 affects H R-induced USP14 p-p65 proinflammatory cytokines potential USP14 preeclampsia
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1
USP14 inhibits H R-induced USP14 p-p65 proinflammatory cytokines potential USP14 preeclampsia. 1 / 1
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1
eidos
"H / R , hypoxia / reoxygenation ; mRNA , messenger RNA ; NF-kappaB , nuclear factor kappa B ; RT-qPCR , quantitative reverse transcription PCR ; TNF-alpha , tumor necrosis factor-alpha ; USP14 , Ubiquitin-specific proteases 14 Depletion of USP14 abrogated H / R-induced upregulation of USP14 , p-p65 , and proinflammatory cytokines To further study the potential role of USP14 in preeclampsia , we aimed to knockdown of USP14 in trophoblast cell lines ."
USP14 affects FRT
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1
USP14 affects ER stress-mediated autophagy
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1
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1
USP14 affects DNA Damage
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1
USP14 inhibits DNA Damage. 1 / 1
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1
USP14 affects Crimmins et al., 2009
|
1
reach
"Our experiments showed that CDK4, CDK6, CDK2, cyclinD1 and phosphorylated Rb were downregulated, while p27 and p15 were increased, by inhibiting USP14 expression or its activity in androgen responsive prostate cancer cells; and conversely, the exactly opposite changes were induced by USP14 overexpression."
USP14 affects 2c-biotin
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1
USP14 aptamers affects USP14
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1
UBIQUITINATED PROTEINS affects USP14
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1
TRCN0000150850 affects USP14
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1
reach
"diaph3 was infected by lentiviruses, respectively, containing the following plasmids : TRCN0000154182 that targets CCT TCG GAT TTA ACC TTA GCT, TRCN0000150850 that targets GCA TGA CAA GTT TGT GAC AAA, TRCN0000150903 that targets GCT CAG TGC TAT TCT CTT TAA, and TRCN0000151280 that targets CGT GTC AGA ATA GCT AAA GAA."
RUNX-CBFbeta heterodimers affects USP14
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1
Proteasome affects K63
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1
Proteasome binds USP14 and K63. 1 / 1
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1
PCAT6 affects USP14
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1
Nxf1 CAST affects USP14
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1
NS4B affects USP14
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1
NM_012094 ] affects USP14
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1
NCIT:C17764 affects HSPA8
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1
MHY-1485 affects USP14
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1
K63-ubiqutination Beclin1 affects USP14
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1
K63 affects USP14
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1
Proteasome binds USP14 and K63. 1 / 1
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1
IU1 treatment affects USP14
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1
HSPA8 affects NCIT:C17764
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1
reach
"Primer sequences were as follows: GAPDH forward TTG AAG TCG CAG GAG ACA ACC; GAPDH reverse ATG TGT CCG TCG TGG ATC; BDNF forward GTG ACA GTA TTA GCG AGT GGG; BDNF reverse GGG ATT ACA CTT GGT CTC GTA G; Fos forward TCC CCA AAC TTC GAC CAT G; Fos reverse CAT GCT GGA GAA GGA GTC G.
Immunofluorescence."
Aroclor 1254 affects USP14
1
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Akt inhibitors affects USP14
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1
reach
"Finally, USP14 S432 is dramatically more phosphorylated in PTEN knockout mouse embryonic fibroblasts (MEFs), which carry high levels of Akt activity, than that of WT MEFs as determined by western blotting using the phospho-USP14 (S432) antibody and phos-tag electrophoresis (XREF_FIG), and the phosphorylation of USP14 S432 was blocked by Akt inhibitors (XREF_FIG)."
reach
"In an angiotensin II (AngII) induced primary neonatal rat cardiomyocyte hypertrophy model, USP14 expression was increased in a time dependent manner, and reduced USP14 deubiquitinase activity or USP14 knockdown resulted in lower expression levels of the myocardial hypertrophy specific marker beta-MHC, and subsequent decreased GSK-3beta phosphorylation."
5-fluorouracil affects USP14
1
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3-methylcholanthrene affects USP14
1
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2c-biotin affects USP14
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1
1
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