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UCHL1 activates Ubiquitin. 21 / 23
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"Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts."
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"Altered solubility ( Wang et al., 2005 ) or nitrosylation of Parkin ( Chung et al., 2004; Yao et al., 2004 ) likely contributes to nigrostriatal dopaminergic degeneration in sporadic PD by neutralizin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Besides TGFbeta blockade, interesting results were shown using LDN57444, a specific small molecule inhibitor, targeting ubiquitin carboxy-terminal hydrolase L1 (UCH-L1)."
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"UCHL1 associates with monoubiqutin, prolongs the half-life of ubiquitin in neurons, and resists apoptotic stress in testicular germ cells [XREF_BIBR, XREF_BIBR]."
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"In contrast to USP14, UCH-L1 is thought to prevent the inappropriate degradation of ubiquitin by sequestering monomeric ubiquitin [XREF_BIBR]."
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"Transgenic overexpression of non-functional UCH-L1 induces podocyte ubiquitin accumulations."
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"In the dimeric form, UCHL1 ligase activity produces Lys-63-linked ubiquitin chains to its substrates."
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"It should be noted, however, that UCH-L1 exogenously expressed in mouse embryonic fibroblasts (MEFs) binds to and increases free ubiquitin [XREF_BIBR]."
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"The I93M mutation in the UCH-L1 gene, which was reported in a German family with autosomal dominant Parkinson 's Disease (PD), leads to a 50% reduction in catalytic of UCH-L1 activity in vitro, implying that loss of UCH-L1 activity may reduce the availability of free ubiquitin, and contribute to an impaired clearance of proteins by the UPS."
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"Through these functions, UCH-L1 can increase the free pool of Ub and, therefore, indirectly affect many ubiquitination dependent cellular activities."
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"Inhibition of UCHL1 using LDN-57444 depletes the hippocampus of monomeric ubiquitin and postsynaptic density protein PSD-95."
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"UCH-L1, depending on its ubiquitination enzyme activity, acts on the target protein and produces free Ub monomers, which participate in the Ub metabolism of target proteins."
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"However, we can not rule out the possibility that ubiquitin depletion by UCHL1 inhibition results in the up-regulation of DUBs acting on GlyT2."
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"Of great interest is also the observation that ATRA may specifically promote upregulation of ubiquitin C-terminal hydrolase-L1 (UCH-L1) [5] , a crucial deubiquitinating enzyme which seems to be specif[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"As Uch-l1 is thought to stimulate protein degradation by generating free monomeric ubiquitin, the gad mutation appears to affect protein turnover."
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"AS Uchl1 enhances translation of UCHL1 (ubiquitin carboxy-terminal hydrolase L1) through an embedded SINE (short interspersed nuclear element) B2 repeat present in AS Uchl1 [XREF_BIBR]."
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"UCH-L1 alters the polyubiquitin chain and increases the availability of free monomeric ubiquitin to the UPS, thus increasing proteasome-dependent proteolysis (61)."
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"Loss of UCHL-1 reduces free ubiquitin, and leads to inadequate ubiquitylation and protein accumulation in neurons (Osaka et al., 2003)."
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"A neuron specific antisense lncRNA, AS Uchl1, could specifically induce the translation of ubiquitin carboxyl-terminal esterase L1 (Uchl1) under certain stress conditions through its complementarity with target mRNA [XREF_BIBR]."
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"The increases in BAG2 (4-fold) and UCHL1 (2.7-fold) Prevent ubiquitin degradation."
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"The relevant control exerted by these DUBs on ubiquitin homeostasis may account for these effects since pharmacological blocking of UCHL1 or UCHL3 reduced the monomeric ubiquitin pool, in turn restricting the ubiquitination of GlyT2 in neurons (XREF_FIG)."
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