IndraLab
Statements
eidos
"Rpn13 , the proteasomal receptor for Uch37 in the proteasome 19S regulatory particle , can activate UCH37 by disrupting dimerization.9 USP14 binds to the regulatory particle Rpn1 to release its catalytic USP domain and polyubiquitin chains of substrate protein.10 Overexpression of Rpn13 or Rpn1 upregulated the COPS5 protein levels and downregulated the p53 protein levels ( Supplementary Fig. S2p ) ."
Proteasome binds USP14 and UCHL5. 4 / 4
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sparser
"In the current study we hypothesize that electrophilic OB compounds, such as 4,4'-diamino-2,2'-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression."
sparser
"Ub-VS, a potent and irreversible inhibitor of UCHL5 and USP14 (and other DUBs), is able to bind to the active site, shifting UCHL5 protein from 37 to 45 kD, or USP14 protein from 60 to 70 kD; in the presence of an inhibitor to such a DUB, the super-shifts can be inhibited ( xref )."
reach
"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."
Proteasome binds USP14 and UCHL5. 4 / 4
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sparser
"In the current study we hypothesize that electrophilic OB compounds, such as 4,4'-diamino-2,2'-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression."
sparser
"Ub-VS, a potent and irreversible inhibitor of UCHL5 and USP14 (and other DUBs), is able to bind to the active site, shifting UCHL5 protein from 37 to 45 kD, or USP14 protein from 60 to 70 kD; in the presence of an inhibitor to such a DUB, the super-shifts can be inhibited ( xref )."
reach
"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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"However, the effect of DRAIC on the combination of UCHL5 and NFRKB was still unclarified, so we detected this combination in oeDRAIC and shDRAIC cell lines, whose results showed that oeDRAIC can significantly reduce the level of NFRKB coprecipitated by UCHL5, while shDRAIC can increase NFRKB binding with UCHL5, which confirmed the speculation that DRAIC may indirectly down-regulate the expression of NFRKB through affecting the deubiquitination induced by UCHL5."
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"Interestingly, immunoprecipitation studies from MG132 treated cells revealed that NFRKB interacted with UCHL5 less in the chromatin fraction than in the nucleoplasm, despite its interactions with INO80 being essentially equivalent in these two fractions (XREF_FIG; for input fractions, see XREF_SUPPLEMENTARY)."
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"Interestingly, a recent study has shown that the proteasomal subunit RPN13 acts as an accessory protein to enhance the activity of the DUB UCH37 toward K48 containing, branched triubiquitin, and this could provide new ways to further explore the assembly and disassembly of these more complex ubiquitin chain types."
| PMC
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"However, the effect of DRAIC on the combination of UCHL5 and NFRKB was still unclarified, so we detected this combination in oeDRAIC and shDRAIC cell lines, whose results showed that oeDRAIC can significantly reduce the level of NFRKB coprecipitated by UCHL5, while shDRAIC can increase NFRKB binding with UCHL5, which confirmed the speculation that DRAIC may indirectly down-regulate the expression of NFRKB through affecting the deubiquitination induced by UCHL5."
reach
"Interestingly, immunoprecipitation studies from MG132 treated cells revealed that NFRKB interacted with UCHL5 less in the chromatin fraction than in the nucleoplasm, despite its interactions with INO80 being essentially equivalent in these two fractions (XREF_FIG; for input fractions, see XREF_SUPPLEMENTARY)."
reach
"On the other hand, Zhang et al. found that lncRNA DRAIC could suppress GC metastasis of GC cells via through influencing NFRKB de-ubiquitination induced by UCHL5 27.EMT is considered to be a core factor of tumor metastasis, and it is clear that a variety of lncRNAs participated in GC development by regulating this cell program."
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"So we further tested the ubiquitination level of NFRKB, and found that the NFRKB ubiquitination level increased significantly after oeDRAIC, which could demonstrate that DRAIC weakens the deubiquitination of NFRKB mediated by UCHL5, and maintains the ubiquitination level of NFRKB and boost the degradation of NFRKB via the ubiquitination-proteasome pathway."
sparser
"The FRF hairpin inserts into the pocket of Uch37 that normally binds ubiquitin, and is clasped in place by binding of the long, C-terminal helix of NFRKB DEU to the catalytic domain of Uch37, which forces the second helix in the Uch37 ULD domain to bend [ xref , xref , xref ] ( xref )."
sparser
"Undoubtedly, DUB activity is a promising strategy for cancer therapy. xref VLX1570 targets the Ub‐USP14 or Ub‐UCHL5 conjugates and is a reversible non‐selective competitive inhibitor of ubiquitin peptidase 14 (USP14) and ubiquitin carboxyl‐terminal hydrolase 5 (UCHL5) in multiple myeloma. xref VLX1570 has been shown to have significant anti‐cancer efficacy with high potency and solubility."
sparser
"To delineate the structural basis of the auto-inhibition of Uch37 and its activation by Rpn13C, we used a Uch37 dimer model derived from its crystal structure and compared it with the structure of the binary complex of ubiquitin-bound Uch37 (PDB ID 4IG7) and its homolog UCH-L3 (PDB ID 1XD3)."
sparser
"Ub-VS, a potent and irreversible inhibitor of UCHL5 and USP14 (and other DUBs), is able to bind to the active site, shifting UCHL5 protein from 37 to 45 kD, or USP14 protein from 60 to 70 kD; in the presence of an inhibitor to such a DUB, the super-shifts can be inhibited ( xref )."
reach
"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."
reach
"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."
UCHL5 affects Proteasome
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UCHL5 binds Proteasome.
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Proteasome binds UCHL5. 10 / 30
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"Considering that UCH-L5 is associated with the proteasome, where the local concentration of ubiquitin is much higher than the average cellular concentration, UCH-L5 might effectively deubiquitinate its substrates for editing purposes before the substrates are degraded by the proteasome."
sparser
"As PSMD1 (scRpn2) encodes for the largest non-ATPase subunit of the 19S regulator lid of the 26S proteasome and this is involved in binding to the deubiquitinase UCH37 (scUCHL5) via the adapter protein ADRM1 (scRpn13), we hypothesized that knockout of PSMD1 may be disrupting the binding of UCH37 to the 26S proteasome, thereby inhibiting its deubiquitinase activity and leading to HIV-1 reactivation xref (Fig. xref )."
Proteasome binds USP14 and UCHL5. 4 / 4
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Proteasome binds UCHL5 and INO80. 1 / 1
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Proteasome binds UCHL5 and 19S. 1 / 1
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UCHL5 activates Proteasome.
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UCHL5 inhibits Proteasome.
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UCHL5 deubiquitinates Proteasome.
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UCHL5 ubiquitinates Proteasome.
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UCHL5 leads to the ubiquitination of Proteasome on S26. 1 / 1
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Proteasome affects UCHL5
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Proteasome binds UCHL5.
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Proteasome binds UCHL5. 10 / 30
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"Considering that UCH-L5 is associated with the proteasome, where the local concentration of ubiquitin is much higher than the average cellular concentration, UCH-L5 might effectively deubiquitinate its substrates for editing purposes before the substrates are degraded by the proteasome."
sparser
"As PSMD1 (scRpn2) encodes for the largest non-ATPase subunit of the 19S regulator lid of the 26S proteasome and this is involved in binding to the deubiquitinase UCH37 (scUCHL5) via the adapter protein ADRM1 (scRpn13), we hypothesized that knockout of PSMD1 may be disrupting the binding of UCH37 to the 26S proteasome, thereby inhibiting its deubiquitinase activity and leading to HIV-1 reactivation xref (Fig. xref )."
Proteasome binds USP14 and UCHL5. 4 / 4
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Proteasome binds UCHL5 and INO80. 1 / 1
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Proteasome binds UCHL5 and 19S. 1 / 1
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Proteasome deubiquitinates UCHL5.
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Proteasome deubiquitinates UCHL5. 5 / 5
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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 ubiquitinates UCHL5.
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Proteasome ubiquitinates UCHL5. 1 / 3
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Proteasome activates UCHL5.
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Proteasome inhibits UCHL5.
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sparser
"The FRF hairpin inserts into the pocket of Uch37 that normally binds ubiquitin, and is clasped in place by binding of the long, C-terminal helix of NFRKB DEU to the catalytic domain of Uch37, which forces the second helix in the Uch37 ULD domain to bend [ xref , xref , xref ] ( xref )."
sparser
"Undoubtedly, DUB activity is a promising strategy for cancer therapy. xref VLX1570 targets the Ub‐USP14 or Ub‐UCHL5 conjugates and is a reversible non‐selective competitive inhibitor of ubiquitin peptidase 14 (USP14) and ubiquitin carboxyl‐terminal hydrolase 5 (UCHL5) in multiple myeloma. xref VLX1570 has been shown to have significant anti‐cancer efficacy with high potency and solubility."
sparser
"To delineate the structural basis of the auto-inhibition of Uch37 and its activation by Rpn13C, we used a Uch37 dimer model derived from its crystal structure and compared it with the structure of the binary complex of ubiquitin-bound Uch37 (PDB ID 4IG7) and its homolog UCH-L3 (PDB ID 1XD3)."
sparser
"Ub-VS, a potent and irreversible inhibitor of UCHL5 and USP14 (and other DUBs), is able to bind to the active site, shifting UCHL5 protein from 37 to 45 kD, or USP14 protein from 60 to 70 kD; in the presence of an inhibitor to such a DUB, the super-shifts can be inhibited ( xref )."
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases"
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases"
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases"
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases"
Rpn13C affects UCHL5
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"A possibility is that INO80 controls UCH-L5 in a temporal manner, where in some circumstances UCH-L5 is inhibited while under other circumstances post-translational modifications (PTMs) and/or conformational changes release the inhibition and activate UCH-L5, allowing for additional layers of regulation."
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases"
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases"
UCHL5 affects Neoplasm Invasiveness
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UCHL5 activates Neoplasm Invasiveness.
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UCHL5 inhibits Neoplasm Invasiveness.
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UCHL5 inhibits Neoplasm Invasiveness. 10 / 11
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"On the other hand, UCH37, the deubiquitinase activated by ADRM1, inhibits glioma cell migration and invasion [42], suggesting that ADRM1 inhibition could have a positive or negative effect on tumor progression, depending on the stage of the tumor.The discovery of a new role for HDAC8 and ADRM1 in MGMT regulation expands the possibilities of the development of new therapies to overcome TMZ resistance in GBM, although several questions about the mechanisms remain to be answered."
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases."
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases."
UCHL5 is modified
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"Smad6 is thought to function preferentially as an inhibitor of BMP, while Smad7 is a general inhibitor of TGFbeta family induced signals (mainly by binding to the TGF-beta type I receptors and preventing phosphorylation of Smads2 and 3, or recruiting ligases that degrade the TGF-beta type I and 2 complexes); however, Smad7 also may enhance TGF-beta, when binding Smad7 to the deubiquitinating enzyme UCH37 [XREF_BIBR])."
B-AP15 affects UCHL5
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UCHL5 affects apoptotic process
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UCHL5 inhibits apoptotic process.
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UCHL5 activates apoptotic process.
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UCHL5 activates apoptotic process. 3 / 3
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"Other studies have also found that b-AP15 inhibition of USP14 and UCHL5 triggers apoptosis in MM cell lines in a time dependent and dose dependent manner.77 Similar cytotoxic effects, as those seen with b-AP15 treatment, occur within myeloma cells when treated with an alternative DUB inhibitor, copper pyrithione.77 Targeting E1 ubiquitin activating enzyme and E3 ubiquitin ligases has synergistic activity with bortezomib on cell lines.78, 79 An inhibitor of USP7, P5091, can interfere with ubiquitin binding and overcome bortezomib resistance invitro and invivo.80 NIMA related kinase 2 (NEK2) overexpression is associated with resistance to multiple drugs and poor prognosis in MM, and NEK2 inhibitor has been shown to decrease proteasome activity.81 Further investigation into its role in Bortezomib resistance is required."
reach
"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."
"Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases."
UCHL5 affects cell population proliferation
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UCHL5 activates cell population proliferation.
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UCHL5 inhibits cell population proliferation.
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UCHL5 affects cell migration
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"Fractionation and immunostaining analyses in Xenopus gastrula showed that Uch37 co-localized with Tcf7 in the nucleus where Tcf7 protein exclusively resides despite both cytoplasmic and nuclear localization of Uch37 protein (XREF_SUPPLEMENTARY), raising the possibility that the nuclear pool of Uch37 regulates Tcf7 to activate Wnt signalling."
WP1130 affects UCHL5
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eidos
"For example , 8-mercapto-N - ( ( tetrahydro-3-furanyl ) methyl ) -4 - quinoline carboxamide , LND-57444 , VLX1570 , ML323 , ( ADC-01 , ADC-03 , HBX41108 , HBX19818 , P5091 , P22077 ) , 9 - ( ethoxyimino ) -9 H-indeno ( 1,2 - b ) pyrazine-2 ,3 - dicarbonitrile , WP1130 , Mitoxantrone and GSK2643943A are able to inhibit PSMD14 , UCHL1 , UCHL5 and USP14 , USP1 , USP7 , USP8 , USP9X , USP11 and USP20 , respectively ."
UCHL5 affects proteolysis
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UCHL5 inhibits proteolysis.
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UCHL5 activates proteolysis.
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RA190 affects UCHL5
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VLX1570 affects UCHL5
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VLX1570 inhibits UCHL5.
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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]."
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)."
VLX1570 binds UCHL5.
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USP14 affects RP
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UCHL5 affects RP
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RP affects USP14
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Benzyl isothiocyanate affects UCHL5
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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."
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."
UCHL5 affects homologous recombination
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"Considering the function of UCH-L5 regulates DNA transcription and mRNA expression of the spliceosome components, the possible reason is that knockdown of UCH-L5 expression upregulates mRNA level of SNRPF which promots the splicing of downstream oncogenes, causing a promotion of oncogenic genes and tumorigenesis."
SERPB12 affects UCHL5
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Proteasome subunit affects UCHL5
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Proteasome subunit binds UCHL5.
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Proteasome subunit activates UCHL5.
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Proteasome subunit activates UCHL5. 2 / 2
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Phenethyl isothiocyanate affects UCHL5
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"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]."
sparser
"In the present study, Sp-UCHL3 mRNA expression in T3 was significantly higher than in the T1 and T2 stages ( p < 0.05), while Sp-UCHL5 mRNA expressions in the three stages of testes development were not significantly different from each other ( p > 0.05), indicating that Sp- UCHL3 and Sp- UCHL5 have different aspects in regulating mechanism of testis development."
UCHL5 affects RA190
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"On the other hand, UCH37, the deubiquitinase activated by ADRM1, inhibits glioma cell migration and invasion [42], suggesting that ADRM1 inhibition could have a positive or negative effect on tumor progression, depending on the stage of the tumor.The discovery of a new role for HDAC8 and ADRM1 in MGMT regulation expands the possibilities of the development of new therapies to overcome TMZ resistance in GBM, although several questions about the mechanisms remain to be answered."
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."
UCHL5 affects Cell Survival
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UCHL5 activates Cell Survival.
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UCHL5 inhibits Cell Survival.
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sparser
"In the present study, Sp-UCHL3 mRNA expression in T3 was significantly higher than in the T1 and T2 stages ( p < 0.05), while Sp-UCHL5 mRNA expressions in the three stages of testes development were not significantly different from each other ( p > 0.05), indicating that Sp- UCHL3 and Sp- UCHL5 have different aspects in regulating mechanism of testis development."
Valproic acid affects UCHL5
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USP14 affects Proteasome
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"We also showed that overexpression of UCH-L5 was associated with a significant increase in caspase-1 activity, while inhibition of UCH-L5 by selective inhibitor [XREF_BIBR] or UCH-L5 knock-down led to decrease in inflammasome dependent IL-1beta release in chicken as well as in human macrophages during infection with Salmonella and during inflammasome activation by lipopolysaccharide (LPS) and nigericin."
RPN13DEUBAD affects UCHL5
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eidos
"On the basis of multiple intermediate structures , it was found that RPN13DEUBAD activates UCH-L5 by positioning its domains while INO80DEUBAD inhibits UCH-L5 by blocking Ub binding.18 Finally , monoUb probes can also be employed to study the mechanism for activation and thioester bond formation in E1s ."
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"On the basis of multiple intermediate structures, it was found that RPN13DEUBAD activates UCH-L5 by positioning its domains while INO80DEUBAD inhibits UCH-L5 by blocking Ub binding.18Finally, monoUb probes can also be employed to study the mechanism for activation and thioester bond formation in E1s."
Proteasome affects USP14
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Pyrithione affects UCHL5
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Pyrithione activates UCHL5.
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Pyrithione inhibits UCHL5.
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Pyrithione inhibits UCHL5. 1 / 1
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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 ]."
Methylmercury chloride affects UCHL5
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BAP15 affects UCHL5
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"In the present study, we revealed, for the first time, evidence of the clinical significance of cytoplasmic UCHL5 expression in ovarian cancer, and demonstrated that bAP15 significantly suppressed UCHL5 in TP53-mutant ovarian cancer cell lines in a dose-dependent manner through downregulation of the TGF-β/Smad signaling pathway (Figure 7)."
UCHL5 affects signal transduction
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UCHL5 affects proteasome subunit
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UCHL5 affects cell cycle
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UCHL5 affects Wnt/β-catenin
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UCHL5 affects TGF-beta-dependent gene
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sparser
"In the current study we hypothesize that electrophilic OB compounds, such as 4,4'-diamino-2,2'-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression."
UCHL5 affects Carcinoma, Endometrioid
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UCHL5 affects 19S
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reach
"Smad6 is thought to function preferentially as an inhibitor of BMP, while Smad7 is a general inhibitor of TGFbeta family induced signals (mainly by binding to the TGF-beta type I receptors and preventing phosphorylation of Smads2 and 3, or recruiting ligases that degrade the TGF-beta type I and 2 complexes); however, Smad7 also may enhance TGF-beta, when binding Smad7 to the deubiquitinating enzyme UCH37 [XREF_BIBR])."
eidos
"In contrast , C-CBL , heat shock protein 90 ( Hsp90 ) , transforming growth factor-beta stimulated clone 22 ( TSC-22 ) , tumor necrosis factor receptor-associated factor 4 ( TRAF4 ) , ubiquitin-specific protease 4 ( USP4 ) , ubiquitin-specific protease 11 ( USP11 ) , ubiquitin-specific protease 15 ( USP15 ) , and UCH37 can stabilize the receptor by blocking the ubiquitination of the receptor [ 103-110 ] , thereby activating the TGF-beta signaling pathway ."
sparser
"In the current study we hypothesize that electrophilic OB compounds, such as 4,4'-diamino-2,2'-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression."
19S affects UCHL5
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Sulforaphane affects UCHL5
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Dibutyl phthalate affects UCHL5
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Cyclosporin A affects UCHL5
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Cyclic peptide affects UCHL5
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Bortezomib affects UCHL5
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Bortezomib inhibits UCHL5. 2 / 2
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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)."
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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)."
Bisphenol A affects UCHL5
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Benzo[a]pyrene affects UCHL5
2
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UPS inhibitor affects UCHL5
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"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) ."
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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)."
UCHL5 affects transcription, DNA-templated
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UCHL5 affects localization
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UCHL5 affects expression
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UCHL5 affects endoplasmic reticulum
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UCHL5 ubiquitinates endoplasmic reticulum.
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UCHL5 leads to the ubiquitination of endoplasmic reticulum. 1 / 1
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UCHL5 inhibits endoplasmic reticulum.
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UCHL5 inhibits endoplasmic reticulum. 1 / 1
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UCHL5 affects cell death
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UCHL5 activates cell death. 2 / 2
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"Overexpression of UCH-L5 (but not overexpression of UCH-L3) for two days prior to the infection with Salmonella for one hour also lead to significant cell death (XREF_FIG), while cell treatment with b-AP15 inhibitor prior to Salmonella infection led to slight increase in cell viability in comparison to vehicle treated cells (XREF_SUPPLEMENTARY)."
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"In this report, we found that PdPT is an inhibitor of multiple DUBs including USP7, USP10, USP14, USP15, USP25 and UCHL5, which contributes to the accumulation of ubiquitinated proteins and subsequent cell death in NSCLC cell lines.Regulated cell death requires activation of various regulators and effectors (23)."
UCHL5 affects VLX1570
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UCHL5 affects TGF-betaR1 protein
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UCHL5 affects Smads
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UCHL5 affects SERPB12
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UCHL5 affects Growth Endometrial Cancer
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UCHL5 affects DRAIC
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UCHL5 affects DNA Breaks, Double-Stranded
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"We also showed that overexpression of UCH-L5 was associated with a significant increase in caspase-1 activity, while inhibition of UCH-L5 by selective inhibitor [ xref ] or UCH-L5 knock-down led to decrease in inflammasome-dependent IL-1β release in chicken as well as in human macrophages during infection with Salmonella and during inflammasome activation by lipopolysaccharide (LPS) and nigericin."
UCHL5 affects 6xHis-UIP1
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2
Smads affects UCHL5
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2
RA-190 affects UCHL5
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2
KDT-11 affects UCHL5
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2
Deubiquitinase affects UCHL5
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2
DRAIC affects UCHL5
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6xHis-UIP1 affects UCHL5
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Unknown mechanism affects UCHL5
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Ubiquitin receptors affects UCHL5
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Trimellitic anhydride affects UCHL5
1
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Trichostatin A affects UCHL5
1
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Sodium(1+) affects UCHL5
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Sodium(1+) activates UCHL5. 1 / 1
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"Additional deleted genes in the region include multiple members of the Regulator of G protein Signaling Gene family (RGS1, RGS2, RGS13, and RGS18) as well as TROVE Domain Family Member 2, Ubiquitin C-terminal Hydrolase L5, and portions of Potassium Sodium Activated Channel Subfamily Member 2 (TROVE2, UCHL5, and KCNT2)."
Sodium arsenite affects UCHL5
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ShRNA interference technology affects UCHL5
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Proteasome ubiquitin affects UCHL5
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Proteasome inhibitor affects UCHL5
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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)."
Proteasomal DEUBAD-containing protein Rpn13 affects UCHL5
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Piperidones affects UCHL5
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Piperidones binds UCHL5. 1 / 1
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Piperidin-2-one affects UCHL5
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Piperidin-2-one inhibits UCHL5. 1 / 1
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Phorbol 13-acetate 12-myristate affects UCHL5
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Paclitaxel affects UCHL5
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Nickel(2+) affects UCHL5
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Nickel(2+) activates UCHL5. 1 / 1
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Monoubiquitin affects UCHL5
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Methylmercury compound affects UCHL5
1
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Isothiocyanate affects UCHL5
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Isothiocyanate inhibits UCHL5. 1 / 1
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Hydroperoxide affects UCHL5
1
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Hsa-miR-6872-3p affects UCHL5
1
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Hsa-miR-657 affects UCHL5
1
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Hsa-miR-6512-5p affects UCHL5
1
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Hsa-miR-5584-5p affects UCHL5
1
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Hsa-miR-5581-3p affects UCHL5
1
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Hsa-miR-539-3p affects UCHL5
1
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Hsa-miR-485-3p affects UCHL5
1
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Hsa-miR-4755-5p affects UCHL5
1
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Hsa-miR-3665 affects UCHL5
1
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Finasteride affects UCHL5
1
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Ethyl methanesulfonate affects UCHL5
1
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Dorsomorphin affects UCHL5
1
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Disodium selenite affects UCHL5
1
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Dimethyl sulfoxide affects UCHL5
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Dimethyl sulfoxide activates UCHL5. 1 / 1
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Dimerization.9 USP14 affects UCHL5
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eidos
"Rpn13 , the proteasomal receptor for Uch37 in the proteasome 19S regulatory particle , can activate UCH37 by disrupting dimerization.9 USP14 binds to the regulatory particle Rpn1 to release its catalytic USP domain and polyubiquitin chains of substrate protein.10 Overexpression of Rpn13 or Rpn1 upregulated the COPS5 protein levels and downregulated the p53 protein levels ( Supplementary Fig. S2p ) ."
Dicrotophos affects UCHL5
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Diarsenic trioxide affects UCHL5
1
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Deubiquitinating function affects UCHL5
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Deubiquitinase adaptor domain affects UCHL5
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1
Coumestrol affects UCHL5
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Catalytic conformation affects UCHL5
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Carbon nanotube affects UCHL5
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B-AP15 is therapeutic molecule affects UCHL5
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Auranofin affects 19S
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Aumdubin affects UCHL5
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Acetaldehyde affects UCHL5
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Acetaldehyde inhibits UCHL5. 1 / 1
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YP_009227200 affects UCHL5
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USP14-3 affects UCHL5
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"In the current study we hypothesize that electrophilic OB compounds, such as 4,4'-diamino-2,2'-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression."
UCHL5 affects translation
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UCHL5 inhibits translation. 1 / 1
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"In order to understand the endogenous function of Uch37 in Xenopus, as suggested by its local enrichment in the mesodermal region of the embryo, we knocked down endogenous Uch37 by injecting antisense morpholino oligonucleotides (Uch37 MO) that specifically and efficiently blocked translation of Uch37 protein (XREF_SUPPLEMENTARY)."
UCHL5 affects signaling receptor activity
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UCHL5 deubiquitinates signaling receptor activity. 1 / 1
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UCHL5 affects repair
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UCHL5 affects protein COPS5
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UCHL5 affects prenatal lethality mice
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UCHL5 affects polyUb chain
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UCHL5 affects piperidones
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Piperidones binds UCHL5. 1 / 1
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UCHL5 affects monoubiquitin
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UCHL5 affects hydrolysis model proteasome substrates
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UCHL5 affects growth endometrial cancer cells
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UCHL5 affects deubiquitinase adaptor domain
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UCHL5 affects beta-Catenin Signaling Pathway
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UCHL5 affects b-AP15
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UCHL5 affects alpha-SMA
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UCHL5 affects YP_009227200
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UCHL5 affects Wnt beta-catenin signaling
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UCHL5 affects UCH domain
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UCHL5 affects TbetaR complex
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UCHL5 affects S14
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UCHL5 affects RPN13 subunit whose C-terminal domain
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UCHL5 affects Polyubiquitin
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UCHL5 inhibits Polyubiquitin 1 / 1
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UCHL5 affects OTX015-R
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UCHL5 affects Neoplasm Metastasis
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UCHL5 inhibits Neoplasm Metastasis. 1 / 1
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"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."
UCHL5 affects K48- linked polyubiquitin chains
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"Whether USP7 and USP47 directly interact with NLRP3 receptor or with other inflammasome component was not investigated.Enzymatic activity of UCHL5 (from the ubiquitin C‐terminal hydrolase family) is also increased after Salmonella enterica serovar Typhimurium infection, and UCHL5 silencing leads to impaired release of IL‐1β after infection 57."
UCHL5 affects Herc4-mediated ubiquitination Smo
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1
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"Most importantly, it was shown that loss of uchl5, the human orthologue of ubh-4, also increases UPS activity and the degradation of proteotoxic proteins in mammalian cells XREF_BIBR, thus further verifying the value of C. elegans as a model organism to evaluate the consequences of UPS modulation."
UCHL5 affects Endometrial Neoplasms
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UCHL5 activates Endometrial Neoplasms. 1 / 1
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UCHL5 affects Endometrial Cancer Cells
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UCHL5 affects ER
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"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 DNA resection
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UCHL5 affects CuPT
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sparser
"The ITC compounds may interact stronger with UCHL5 than to USP14 since more favorable bonding interactions were found upon analyzing the general decrease of free energy across the three compounds corresponding to xref . xref suggests interaction of BITC with the active site CYS-88 of UCHL5 through two formed bonds."
UCHL5 affects 2c-biotin
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UCHL5 affects 293T
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UCHL5 affects (ULD) domain
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UCH domain affects UCHL5
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S14 affects UCHL5
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RPN13 affects (ULD) domain
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RPN13 subunit whose C-terminal domain affects UCHL5
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RP affects PSMD14
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Proteasome affects INO80
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Proteasome affects 19S
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Proteasome binds UCHL5 and 19S. 1 / 1
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Myc-Ub affects UCHL5
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1
Infections affects UCHL5
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Infections increases the amount of UCHL5. 1 / 1
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INO80 affects Proteasome, and UCHL5
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eidos
"In contrast , C-CBL , heat shock protein 90 ( Hsp90 ) , transforming growth factor-beta stimulated clone 22 ( TSC-22 ) , tumor necrosis factor receptor-associated factor 4 ( TRAF4 ) , ubiquitin-specific protease 4 ( USP4 ) , ubiquitin-specific protease 11 ( USP11 ) , ubiquitin-specific protease 15 ( USP15 ) , and UCH37 can stabilize the receptor by blocking the ubiquitination of the receptor [ 103-110 ] , thereby activating the TGF-beta signaling pathway ."
GAS2DN affects UCHL5
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E3_Ub_ligase affects UCHL5
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E3_Ub_ligase ubiquitinates UCHL5-C88A. 1 / 1
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Degrasyn affects UCHL5
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DUB inhibitor affects UCHL5
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sparser
"In the current study we hypothesize that electrophilic OB compounds, such as 4,4'-diamino-2,2'-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression."
CuPT affects UCHL5
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CdPT affects UCHL5
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Carcinoma, Endometrioid affects UCHL5
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Carcinoma, Endometrioid inhibits UCHL5. 1 / 1
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sparser
"The ITC compounds may interact stronger with UCHL5 than to USP14 since more favorable bonding interactions were found upon analyzing the general decrease of free energy across the three compounds corresponding to xref . xref suggests interaction of BITC with the active site CYS-88 of UCHL5 through two formed bonds."
COPS5 affects 293T
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sparser
"We also showed that overexpression of UCH-L5 was associated with a significant increase in caspase-1 activity, while inhibition of UCH-L5 by selective inhibitor [ xref ] or UCH-L5 knock-down led to decrease in inflammasome-dependent IL-1β release in chicken as well as in human macrophages during infection with Salmonella and during inflammasome activation by lipopolysaccharide (LPS) and nigericin."
Aroclor 1254 affects UCHL5
1
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AgDT affects UCHL5
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1
ADRM1 affects monoubiquitin
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1
4-phenylbutyric acid affects UCHL5
1
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2c-biotin affects UCHL5
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1
293T affects UCHL5
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1
19S affects auranofin
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19S affects Proteasome, and UCHL5
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Proteasome binds UCHL5 and 19S. 1 / 1
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17alpha-ethynylestradiol affects UCHL5
1
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1.171 affects UCHL5
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1,4-dithiothreitol affects UCHL5
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1,4-dithiothreitol activates UCHL5. 1 / 1
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"They further showed that some DUBs that have been exposed to ROS can have different responses to reduction through DTT treatment, with some being activated by DTT (e.g., USP8, USP10, and USP19), some having only enhancement of activity in the presence of DTT (e.g., USP7, CYLD, and UCHL5), and others exhibiting no activity, despite the presence of a reducing agent (e.g., USP1, USP22, and A20) (35)."
(ULD) domain affects UCHL5
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1
(-)-epigallocatechin 3-gallate affects UCHL5
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(-)-epigallocatechin 3-gallate increases the amount of UCHL5. 1 / 1
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"Analysis of the associated and non associated DUBs, such as UCHL2, USP14, UCH37, and UBC9 and DUB associated with core 20S proteasome (PSMD13) in RA-FLS showed that in the presence of IL-1beta, EGCG increased the expression of UCH37 and USP14, DUBs known to preferentially hydrolyze K48 linked polyubiquitin chains, with a marginal effect on unassociated DUB such as UCHL2 (XREF_FIG)."
3,3',4,4',5-pentachlorobiphenyl affects UCHL5
1
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