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USP14 inhibits Proteasome. 45 / 51
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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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"Inhibition of USP14 activity reduced MNV-1 infection but WP1130 did not inhibit proteasome activity."
22792064
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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."
28509417
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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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"A small molecule inhibitor of USP14 (IU1; Fig. 9 ) has been described which indeed enhances proteasome function in cells ( Lee et al., 2010 )."
25444757
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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 ) ."
33791305
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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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"Previous studies reported that USP14 can inhibit the proteasome and protein turnover in cells XREF_BIBR."
27629392
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"This implies that USP14 prevents the proteasome from assuming the conformation of RPN11-catalysed deubiquitylation."
35477760
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"Therefore, a small-molecule inhibitor of Usp14 might enhance proteasome activity."
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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"This observation suggests that inhibitors of USP14 could potentially augment proteasome activity [93]."
38739934
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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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"USP14 inhibits proteasome activity by trimming the ubiquitin chain on the substrate."
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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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"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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"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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"USP14 is reversely associated with the proteasome to trim K48 Ub chains and negatively regulates proteasome activity."
28029679
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"Inhibition of USP14 activity by IU1 enhanced proteasome activity 64, thus reduced oxidative stress-induced cell death in vitro 65."
31244932
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"Hence, we speculated that Aur inhibited androgen receptor signaling by PKC pathway and promoted the degradation of androgen receptor result from USP14 and UCHL5 inhibition.Interestingly, inhibition of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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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"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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"Enhancement of proteasome activity by a small-molecule inhibitor of USP14."
22520753
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"Ubp6/USP14 was shown to inhibit proteasome activity by delaying the breakdown of proteins by the proteasome ( Lee et al., 2010, 2011 )."
25444757
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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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"Enhancement of proteasome activity by a small-molecule inhibitor of USP14."
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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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"This decrease in presynaptic transmission with a Usp14 genetic mutant potentially explains the long-term memory deficits in mice treated with a Usp14 inhibitor.Usp14 itself acts as a regulator of proteasome activity, with overexpression of Usp14 inhibiting proteasome function [172]."
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"Ubp6 (human USP14) shortens polyubiquitin chains (94) and inhibits proteasome activity (93) possibly to avoid futile degradation of essential proteins during stress.Interestingly, the CP and RP seem to be separately sequestered into PSGs, the CP by Blm10 (28) and the RP by Spg5 (95)."
35636514
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"An inhibitor of USP14 has been shown to increase activity of the proteasome, which may be of use in disease states where proteotoxic stress is archetypal [ 30 ]."
32200025
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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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"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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"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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"It will be worthwhile to determine whether the activity of USP14 also underlies the reduction in proteasome activity after autophagy induction.Our results indicate that the regulatory circuit for prot[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30021169
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"IU1, a small molecule inhibitor of USP14, increased proteasome activity and proteasomal degradation of TAU, a hallmark protein in AD (Boselli et al., 2017)."
36926679
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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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"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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"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."
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"We also report that Usp14 can inhibit proteasome function noncatalytically, as previously observed for its yeast ortholog Ubp6."
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"Enhancement of Proteasome Activity by a Small-Molecule Inhibitor of Usp14."
20829789
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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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"USP14 inhibition activates the proteasome, removes tau oligomers, and promotes huntingtin aggregation [19], suggesting that it contributes to aggregate deposition in neurodegenerative diseases."
38780644
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"Enhancement of Proteasome Activity by a Small-Molecule Inhibitor of Usp14."
29995557
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"Therefore, the ability of USP14 and Ubp6 to inhibit the proteasome in a non-catalytic manner relies on both UBL and USP domains of these proteins (Hanna et al., 2006; Kim and Goldberg, 2017; Hung et al., 2022; Zhang et al., 2022)."
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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."
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