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USP14 inhibits Proteasome. 30 / 35
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"However, USP14 does not appear to strongly antagonize proteasome function in Xenopus extract, as treatment of extract with UbVS or the USP14 specific inhibitor IU1 did not appreciably enhance turnover of pre-ubiquitinated cyclin."
22286100
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"Inhibition of USP14 activity reduced MNV-1 infection but WP1130 did not inhibit proteasome activity."
22792064
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"These results indicate that altered proteasome function caused by the loss of Usp14 results in widespread changes in the levels of activated stress kinases that have been implicated in tau phosphorylation."
23144711
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"Given that several studies have confirmed that USP14 can inhibit the proteasome in vitro [XREF_BIBR, XREF_BIBR, XREF_BIBR] and can inhibit protein turnover in cells [XREF_BIBR] the investigation and development of novel anticancer therapy based on inhibition of proteasome deubiquitinating activity or regulation of protein turnover is indicated."
23702845
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"Inhibition of Usp14 elevates proteasome activity in mouse fibroblasts cell culture.29 Our study suggests that Usp14 predominantly affects beta5 activity in C2C12 cell culture."
28675601
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"These findings reveal that in vivo proteasome function is limited by Usp14 dependent chain trimming, implying that otherwise competent substrates of the proteasome can be rejected when chain trimming is faster than competing steps leading to substrate degradation."
20829789
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"Inhibition of USP14 by the small molecule IU1 has been shown to enhance proteasome activity, which has been suggested as a novel therapeutic strategy."
23011887
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"Because K48 linked ubiquitin chains are a robust biomarker of ubiquitin proteasome system function [XREF_BIBR], and we found no difference in the catalytic capacity of TgUsp14CA and wild type proteasomes in vitro, it is unlikely that USP14 inhibition in the nervous system causes global alterations in proteasome activity."
25575639
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"Furthermore, inhibition of USP14 enhanced the activity of the 26S proteasome, while significantly decreased cellular autophagy, especially the autophagosome-lysosome fusion, which constituted compensatory negative feedback between UPS and autophagy (Table 2) (Kim et al., 2018a)."
35069211
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"The DUB USP14 suppresses turnover of Tau and TDP-43 in mouse embryonic fibroblasts (MEFs) by impairing the protea-some;"
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"Previous studies reported that USP14 can inhibit the proteasome and protein turnover in cells XREF_BIBR."
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"Our recent discovery of USP14 inhibitors clearly suggests that proteasomal DUBs can be valid pharmacological targets because USP14 inhibition may potentiate proteasome mediated protein quality control."
23788557
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"USP14 as a component of proteasome-associated deubiquitinating enzyme complex can eliminate ubiquitins from proteasome-bound substrates and inhibit the proteasome non-catalytically ( Chen et al ., 2018 ) ."
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"USP14 negatively regulates proteasome activity by ubiquitin chain disassembly as well as by a noncatalytic mechanism XREF_BIBR - XREF_BIBR."
27074503
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"USP14 is reversely associated with the proteasome to trim K48 Ub chains and negatively regulates proteasome activity."
28029679
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"Proteasome dysfunction induced by the loss of Usp14 results in a significant increase in the levels of phosphorylated tau in the brains of the ax J mice."
23144711
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"To verify that Usp14 inhibits the proteasome in cells, we expressed Usp14 variants in usp14 -/- murine embryonic fibroblasts (MEFs), together with proteasome substrates."
20829789
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"USP14 suppression enhanced proteasome activity and induced the degradation of abnormal proteins such as tau and Ataxin-3 [ 150 ] ."
| PMC
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"To explore the possibility that inhibitory USP14 aptamers might enhance proteasome activity, we used suc-LLVY-AMC, a fluorogenic reporter substrate of 26S proteasomes."
26041011
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"A highly promising approach to restore proteostatic imblance is based on USP14, a DUBs that inhibits proteasome mediated degradation by trimming the polyubiquitin chain on the client proteins (XREF_FIG) [XREF_BIBR]."
23339312
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"As Usp14 negatively regulates proteasome activity by ubiquitin chain disassembly as well as by a noncatalytic mechanism [XREF_BIBR], oleocanthal, in the presence of oxidative stress, has two opposite effects : on one side, it up-regulates the proteasome and, on the other side, it up-regulates Usp14, abrogating the suggested enhancement of the proteasome activity."
30096819
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"Enhancement of Proteasome Activity by a Small-Molecule Inhibitor of Usp14."
20829789
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"In particular, deubiquitinating enzymes Uch37 and Usp14, being physically associated with the proteasome, may suppress proteasome activity through deubiquitinating a subset of ubiquitinated substrates, once the substrate is docked at the proteasome."
23994620
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"Further studies on the mechanism by which Usp14 inhibition alters ubiquitination and degradation of cGAS may help elucidate the mechanism by which Usp14 modulates autophagy.A corollary to the hypothes[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28988953
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"Moreover, USP14 was also shown to inhibit proteasome mediated degradation by cleaving ubiquitin chains conjugated to substrates 68."
33483467
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"We also report that Usp14 can inhibit proteasome function noncatalytically, as previously observed for its yeast ortholog Ubp6."
20829789
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"USP14 inhibits proteasome activity by trimming the ubiquitin chain on the substrate."
27028664
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"Recently, small-molecule inhibitors of USP14, a proteasome interacting deubiquitinating enzyme that antagonizes the degradation of ubiquitinated substrates, have been shown to enhance proteasome activity and facilitate the clearance of misfolded and aggregated proteins in cells."
25907364
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"Ubiquitin specific peptidase 14 has been proven to inhibit the proteasome in vitro.21 Ubiquitinated tau is a substrate protein for proteasomal degradation.22 Expressing wild-type USP14 in Usp14 -/- murine embryonic fibroblasts could increase tau expression levels, indicating that USP14 suppressed the ability of the proteasome to degrade tau.23 The deubiquitinating activity of the 19S regulatory particle has recently been proven to be a promising target for cancer treatment."
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"Therefore, a small-molecule inhibitor of Usp14 might enhance proteasome activity."
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