IndraLab
Statements
sparser
"For example, it is not clear how hRpn13 activates Uch37, but it is possible that its strong ubiquitin-binding affinity contributes by increasing Uch37’s affinity for its substrates when in the hRpn13 complex and by helping to orient neighboring ubiquitin moieties in a configuration that is optimal for hydrolysis."
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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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"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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"Despite a potential functional interaction between USP14 and UCHL5, it does not appear to be linked to proteasome inhibition or ubiquitin depletion.We explored possible links between the two DUBs through common physical interactors identified from curated experiments using the BioGRID protein interaction database ."
Proteasome binds UCHL5 and USP14. 4 / 4
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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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"Despite a potential functional interaction between USP14 and UCHL5, it does not appear to be linked to proteasome inhibition or ubiquitin depletion.We explored possible links between the two DUBs through common physical interactors identified from curated experiments using the BioGRID protein interaction database ."
Proteasome binds UCHL5 and USP14. 4 / 4
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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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"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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"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."
"DRAIC combined with <span class="match term0">UCHL5</span> and attenuated binding of <span class="match term0">UCHL5</span> and <span class="match term1">NFRKB</span>, meanwhile promoting the degradation of <span class="match term1">NFRKB</span> via ubiquitination, and then inhibited the proliferation and metastasis of GC cells, which can be rescued by oe<span class="match term1">NFRKB</span>"
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"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."
UCHL5 affects Proteasome
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UCHL5 binds Proteasome.
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UCHL5 binds Proteasome. 10 / 41
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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."
Proteasome binds UCHL5 and USP14. 4 / 4
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UCHL5 binds Proteasome and INO80. 1 / 1
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UCHL5 binds Proteasome and 19S. 1 / 1
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UCHL5 activates Proteasome.
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UCHL5 inhibits 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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"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."
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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
"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
"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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"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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"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."
Proteasome affects UCHL5
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Proteasome binds UCHL5.
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UCHL5 binds Proteasome. 10 / 41
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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."
Proteasome binds UCHL5 and USP14. 4 / 4
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UCHL5 binds Proteasome and INO80. 1 / 1
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UCHL5 binds Proteasome and 19S. 1 / 1
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Proteasome deubiquitinates UCHL5.
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Proteasome deubiquitinates UCHL5. 6 / 6
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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 UCHL5.
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Proteasome activates UCHL5.
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Proteasome activates UCHL5. 1 / 2
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"After HCV infection, Recombinant Ubiquitin Carboxyl Terminal Hydrolase (UCHL5) mediates the de-ubiquitination of NLRP3 (Wang W. et al., 2020), while the stimulator of interferon genes (STING), which functions as an NLRP3 activator, interacts with NLRP3 and then inhibits the ubiquitination of NLRP3 (Siu et al., 2019)."
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
"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
"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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"The 26S proteasome-mediated degradation of a ubiquitinated protein target involves an initial Ub recognition step that is primarily mediated by subunits Rpn10 and Rpn13 of the 19S RP [8,9], followed by deubiquitination of the substrate by Rpn11 or one of two other proteasome-associated deubiquitinating enzymes (DUBs), UCH37 and USP14."
"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"
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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."
Rpn13C affects UCHL5
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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 Rpn13C
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"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 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. 7 / 7
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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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"Therefore, our current research may allow targeting UCHL5 and USP14 in 19S regulatory particle for anti-cancer drug development.b-AP15 was reported to inhibit tumor cell growth and induce cell apoptosis, and displays anti-tumor role in multiple tumor cell models without inhibiting 26S proteasomes proteolytic activities."
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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."
UCHL5 affects Neoplasm Invasiveness
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UCHL5 activates Neoplasm Invasiveness.
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UCHL5 activates Neoplasm Invasiveness. 10 / 11
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UCHL5 activates Neoplasm Invasiveness. 4 / 4
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"In contrast to BAP1, which inhibits RCC by upregulation of STING activity and activation of interferon, UCHL5 promotes RCC by regulating immune infiltration and antigen presentation of B cells, and its increased level in RCC blood samples suggest its potential as a prognostic marker."
UCHL5 inhibits Neoplasm Invasiveness.
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UCHL5 inhibits Neoplasm Invasiveness. 10 / 10
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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."
B-AP15 affects UCHL5
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"Although the results obtained by D’Arcy
and colleagues demonstrate that b-AP15 is an inhibitor of USP14/UCH-37, two unrelated cysteine protease enzymes from
different DUB families, the chemical structure of b-AP15 suggests
additional proteins may be targeted by this compound and its analogues."
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"XREF_BIBR These results have also been further supported by the findings of the Feng et al XREF_BIBR study which have shown that b-AP15 inhibits the deubiquitylating activity of USP14 and UCHL5 enzymes, triggering apoptosis in MM cell lines in a time dependent and dose dependent manner."
"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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WP1130 affects UCHL5
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WP1130 inhibits 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 ."
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"These findings indicate that PR-619 inhibits DUB action independently of MSK1, but WP1130 inhibits DUB action, which is essential for MSK1 to increase Snail protein expression.While PR-619 is a general DUB inhibitor that inhibits many DUBs, WP1130 inhibits a subgroup of DUBs, including UCHL1, UCHL5, USP5, USP9X and USP14 (ref."
WP1130 activates UCHL5.
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"It has been previously reported that WP1130 targets the deubiquitinases (DUBs) USP5, USP9X, USP14, UCHL1 and UCHL5.27 In order to test whether these DUBs are involved in the regulation of ULK1 expression levels, we transfected HEK293 cells simultaneously with the corresponding siRNAs and analyzed endogenous ULK1 expression after 48 and 72 h, respectively However, we could not detect any alterations of ULK1 expression levels."
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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."
VLX1570 affects UCHL5
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VLX1570 inhibits 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)."
VLX1570 binds UCHL5.
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VLX1570 activates UCHL5.
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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."
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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."
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"B-AP15, an inhibitor of USP14 and UCHL5, can cooperate with imatinib to inhibit the growth of BCR-ABL-WT and BCR-ABL-T315I CML cell lines, CML xenograft tumor, and primary CML cells.154 Meanwhile, in another study, they found that piperlongumine, isolated from piper longum L., can target USP14 and UCHL5 to inhibit the proteasome function of CML cells with or without T315I mutation, weaken the cell viability of CML cell line, induce apoptosis, and inhibit the growth of transplanted tumor."
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"The loaded Auranofin in PCN224@Au could be released to down-regulate the deubiquitinating enzymes (e.g., CyclinB, USP14 and UCH37), blockade the deubiquitinating process and promote the accumulations of proteasomal substrate proteins (e.g., c-Jun and p21) to encourage proteasomal degradation of ubiquitinated target proteins."
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"In detail, Auranofin release from PCN224@Au down-regulated the deubiquitinating enzymes (e.g., CyclinB, USP14 and UCH37) and promoted the proteasomal substrate proteins (e.g., c-Jun and p21) accumulations via activating MAP3Ks, CDK and p53 pathways, which drove ubiquitinated target degradation by proteasome."
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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]."
UCHL5 affects proteolysis
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UCHL5 inhibits proteolysis.
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UCHL5 activates proteolysis.
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UCHL5 affects cell migration
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UCHL5 affects Wnt/β-catenin
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"Our study’s findings demonstrate that altering UCHL5 expression can control the mRNA expression levels of markers associated with metabolism, including GLUT1, PKM2, HK2, and LDHA, and further encourage the growth of glycolysis.In this work, we discovered that UCHL5 triggers Wnt/β-catenin to activate glycolysis."
RA190 affects UCHL5
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UCHL5 affects glycolytic process
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UCHL5 activates glycolytic process. 9 / 9
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"Our study’s findings demonstrate that altering UCHL5 expression can control the mRNA expression levels of markers associated with metabolism, including GLUT1, PKM2, HK2, and LDHA, and further encourage the growth of glycolysis.In this work, we discovered that UCHL5 triggers Wnt/β-catenin to activate glycolysis."
UCHL5 affects Neoplasm Metastasis
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"To address whether downregulation of proteasome-associated DUBs ubh-4, the uchl5 homolog, and usp-14 induces a tissue-specific or systemic effect on autophagy in C. elegans, we downregulated ubh-4 and usp-14 by RNAi-feeding and analyzed autophagy in intestinal cells, hypodermal seam cells and pharynx (Fig. 4A)."
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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Benzyl isothiocyanate affects UCHL5
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"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."
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."
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"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."
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."
UCHL5 affects RP
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"Furthermore, we demonstrated that pro-SFTPB negatively regulates PGK1 protein levels by binding to ADRM1 and suppressing complex formation by ADRM1, hRpn2 and UCH37; this weakened ADRM1/hRpn2/UCH37 complex-mediated PGK1 deubiquitination, thereby facilitating degradation of the PGK1 protein in NSCLC."
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"Importantly, we found colocalization of ADRM1 and PGK1 (Fig. 5d), and silencing of ADRM1 or UCH37 decreased PGK1 protein levels (Fig. 5e) and increased PGK1 ubiquitination in NSCLC cells (Fig. 5f), suggesting that the ADRM1/UCH37 axis is involved in the regulation of PGK1 deubiquitination."
SERPB12 affects UCHL5
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RP affects UCHL5
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Deubiquitinase affects UCHL5
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Deubiquitinase inhibits UCHL5.
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Deubiquitinase activates UCHL5.
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Phenethyl isothiocyanate affects UCHL5
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Cyclic peptide affects UCHL5
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Cyclic peptide inhibits UCHL5. 5 / 5
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"Moreover, we show that the treatment of cells with our cyclic peptide results in the accumulation of ubiquitinated substrates without any toxicity on the cells caused by the peptide, suggesting that the cyclic peptide permeates the cell membrane and potentially inhibits the activity of UCH-L5."
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"Taken together with the previous data from IC assays, activity-based competition assays, and the activity-based DUB profiling, we showed that the cyclic peptide 2 preferably inhibited UCH-L5 compared to other DUBs in the UCH family and did not show a significant effect on the probe-labeling of other DUBs in MCF7 cell lysate."
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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"New research shows that the interaction of Prdx1 with UCH37 attenuates the effects of UCH37 on cell migration and invasion; this interaction may be through the formation of a complex rather than the deubiquitination of UCH37 itself, but the mechanism of the two on the development of liver cancer has not yet been elucidated ( xref )."
UCHL5 affects Cell Survival
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UCHL5 activates Cell Survival.
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UCHL5 inhibits Cell Survival.
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"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."
PTIR1 affects UCHL5
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"New research shows that the interaction of Prdx1 with UCH37 attenuates the effects of UCH37 on cell migration and invasion; this interaction may be through the formation of a complex rather than the deubiquitination of UCH37 itself, but the mechanism of the two on the development of liver cancer has not yet been elucidated ( xref )."
Valproic acid affects UCHL5
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"Hence we concluded that among the other members of the UCH family, the cyclic β-sheet peptide 2 inhibits UCH-L5 most efficiently.To further investigate whether the cyclic peptide 2 inhibits the activity of Rpn11, the metalloprotease DUBs found in the 19S cap of the 26S proteasome, we carried out a standard fluorescence polarization assay using a Ubiquitin-Fluorescence Polarization (Ub-FP) substrate containing Ub linked by an isopeptide bond to a TAMRA-labelled Ub peptide, comprising residues 41 to 54 of Ub (Supplementary Figure S3A)."
Bisphenol A 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)."
USP14 affects RP
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4
USP14 affects Proteasome
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4
UCHL5 affects proteasome subunit
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3
1
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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."
UCHL5 affects Carcinoma, Endometrioid
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4
RPN13DEUBAD affects UCHL5
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2
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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.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."
RP affects USP14
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4
Proteasome affects USP14
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4
Sulforaphane affects UCHL5
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1
Sulforaphane inhibits UCHL5.
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1
Sulforaphane deubiquitinates UCHL5.
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Sulforaphane deubiquitinates UCHL5. 1 / 1
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1
Sodium arsenite affects UCHL5
3
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Sodium arsenite increases the amount of UCHL5.
2
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Sodium arsenite decreases the amount of UCHL5.
1
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Methylmercury chloride affects UCHL5
3
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UCHL5 affects localization
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3
UCHL5 affects inflammatory response
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3
UCHL5 affects endoplasmic reticulum
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3
UCHL5 inhibits endoplasmic reticulum.
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2
UCHL5 inhibits endoplasmic reticulum. 2 / 2
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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 ubiquitinates endoplasmic reticulum.
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UCHL5 leads to the ubiquitination of endoplasmic reticulum. 1 / 1
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UCHL5 affects cell cycle
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UCHL5 affects TGF-beta-dependent gene
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3
UCHL5 affects Stomach Neoplasms
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3
UCHL5 activates Stomach Neoplasms.
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UCHL5 activates Stomach Neoplasms. 2 / 2
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2
UCHL5 inhibits Stomach Neoplasms.
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UCHL5 bound to NFRKB inhibits Stomach Neoplasms. 1 / 1
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UCHL5 affects PTIR1
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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 DRAIC
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3
UCHL5 affects DNA-templated transcription
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2
UCHL5 affects DNA Breaks, Double-Stranded
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3
UCHL5 affects Carcinoma, Hepatocellular
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3
UCHL5 affects ATP hydrolysis activity
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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 ."
DUB inhibitor affects UCHL5
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3
DRAIC affects UCHL5
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3
Small molecule b-AP15 affects UCHL5
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2
Pyrithione affects UCHL5
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2
Proteasome ubiquitin affects UCHL5
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2
Proteasome ubiquitin receptor affects UCHL5
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2
HRpn2 affects UCHL5
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2
Folic acid affects UCHL5
2
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Dibutyl phthalate affects UCHL5
2
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Deubiquitinase adaptor domain affects UCHL5
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2
Cyclosporin A affects UCHL5
2
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Benzo[a]pyrene affects UCHL5
2
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All-trans-retinoic acid affects UCHL5
2
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UCHL5 affects signal transduction
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2
UCHL5 affects hRpn2
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2
UCHL5 affects expression
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2
UCHL5 affects deubiquitinase adaptor domain
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2
UCHL5 affects cell growth
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2
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)."
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UCHL5 affects VLX1570
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2
UCHL5 affects Smads
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2
UCHL5 affects SERPB12
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1
1
UCHL5 affects Hypertrophy
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2
UCHL5 affects Carcinogenesis
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1
1
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
6xHis-UIP1 affects UCHL5
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2
Zinc pyrithione affects UCHL5
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1
Zinc pyrithione inhibits UCHL5. 1 / 1
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1
Sodium(1+) affects UCHL5
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1
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)."
ShUCHL5 #1 and #2 affects UCHL5
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1
Proteasome inhibitor affects UCHL5
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1
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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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1
Paclitaxel affects UCHL5
1
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Nickel(2+) affects UCHL5
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1
Nickel(2+) activates UCHL5. 1 / 1
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1
Metabolite affects UCHL5
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1
Metabolite inhibits UCHL5. 1 / 1
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1
Hsa-miR-539-3p affects UCHL5
1
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Ethyl methanesulfonate affects UCHL5
1
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Doxycycline affects UCHL5
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1
Doxycycline activates UCHL5. 1 / 1
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1
Dimethyl sulfoxide affects UCHL5
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1
Dimethyl sulfoxide activates UCHL5. 1 / 1
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1
Deubiquitinating function affects UCHL5
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1
Catalytic conformation affects UCHL5
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1
Bortezomib affects UCHL5
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1
Bortezomib inhibits UCHL5. 1 / 1
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1
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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)."
B-AP15 is therapeutic molecule affects UCHL5
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1
Aumdubin affects UCHL5
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1
Aristolochic acid A affects UCHL5
1
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UCHL5 affects β-catenin inhibitors
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1
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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1
UCHL5 affects prenatal lethality mice
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1
UCHL5 affects polyUb chain
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1
UCHL5 affects nitric oxide
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UCHL5 activates nitric oxide. 1 / 1
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UCHL5 affects growth endometrial cancer cells
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1
UCHL5 affects cell movement
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UCHL5 inhibits cell movement. 1 / 1
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UCHL5 affects alpha-SMA
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1
UCHL5 affects Vascular Remodeling
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1
UCHL5 inhibits Vascular Remodeling. 1 / 1
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1
UCHL5 affects TbetaR complex
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1
UCHL5 affects Smad7-Smurf1
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1
UCHL5 affects Smad1/5/9
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1
UCHL5 affects S14
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1
UCHL5 affects RPN13 subunit whose C-terminal domain
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1
UCHL5 affects Osteosarcoma
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1
UCHL5 activates Osteosarcoma. 1 / 1
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"We have previously shown that Uchl5 depletion enhances proteasomal substrate degradation in human U-2 OS (osteosarcoma) cells and that the C. elegans homolog UBH-4 regulates proteasome activity in C. elegans intestine, and affects the lifespan and health span of the animal (Matilainen et al., 2013)."
UCHL5 affects K48- linked polyubiquitin chains
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1
UCHL5 affects Herc4-mediated ubiquitination Smo
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1
UCHL5 affects Endometrial Cancer Cells
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1
UCHL5 affects Deubiquitinase
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1
UCHL5 activates Deubiquitinase. 1 / 1
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1
UCHL5 affects DNA resection
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1
UCHL5 affects CuPT
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1
UCHL5 affects BCR-ABL-WT
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1
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"B-AP15, an inhibitor of USP14 and UCHL5, can cooperate with imatinib to inhibit the growth of BCR-ABL-WT and BCR-ABL-T315I CML cell lines, CML xenograft tumor, and primary CML cells.154 Meanwhile, in another study, they found that piperlongumine, isolated from piper longum L., can target USP14 and UCHL5 to inhibit the proteasome function of CML cells with or without T315I mutation, weaken the cell viability of CML cell line, induce apoptosis, and inhibit the growth of transplanted tumor."
UCHL5 affects BCR-ABL-T315I
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1
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"B-AP15, an inhibitor of USP14 and UCHL5, can cooperate with imatinib to inhibit the growth of BCR-ABL-WT and BCR-ABL-T315I CML cell lines, CML xenograft tumor, and primary CML cells.154 Meanwhile, in another study, they found that piperlongumine, isolated from piper longum L., can target USP14 and UCHL5 to inhibit the proteasome function of CML cells with or without T315I mutation, weaken the cell viability of CML cell line, induce apoptosis, and inhibit the growth of transplanted tumor."
reach
"B-AP15, an inhibitor of USP14 and UCHL5, can cooperate with imatinib to inhibit the growth of BCR-ABL-WT and BCR-ABL-T315I CML cell lines, CML xenograft tumor, and primary CML cells.154 Meanwhile, in another study, they found that piperlongumine, isolated from piper longum L., can target USP14 and UCHL5 to inhibit the proteasome function of CML cells with or without T315I mutation, weaken the cell viability of CML cell line, induce apoptosis, and inhibit the growth of transplanted tumor."
UCHL5 affects 293T
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1
UCHL5 affects 19S
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1
UCHL5 binds Proteasome and 19S. 1 / 1
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S14 affects UCHL5
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1
RPN13 subunit whose C-terminal domain affects UCHL5
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1
Proteasome affects INO80
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1
Proteasome affects 19S
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1
UCHL5 binds Proteasome and 19S. 1 / 1
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PCN224 affects UCHL5
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1
Myc-Ub affects UCHL5
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1
Methylmercury Compounds affects UCHL5
1
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ML364 affects UCHL5
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1
INO80 affects Proteasome, and UCHL5
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1
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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1
Degrasyn affects UCHL5
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1
CdPT affects UCHL5
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1
Carcinoma, Endometrioid affects UCHL5
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1
Carcinoma, Endometrioid inhibits UCHL5. 1 / 1
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1
COPS5 affects 293T
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1
293T affects UCHL5
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1
19S affects UCHL5
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UCHL5 binds Proteasome and 19S. 1 / 1
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17alpha-ethynylestradiol affects UCHL5
1
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1,4-dithiothreitol affects UCHL5
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1
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)."
1,2-dimethylhydrazine affects UCHL5
1
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(-)-epigallocatechin 3-gallate affects UCHL5
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1
(-)-epigallocatechin 3-gallate increases the amount of UCHL5. 1 / 1
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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)."
4,4'-sulfonyldiphenol affects UCHL5
1
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1
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