IndraLab

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"However, upon binding a Ub conjugate, USP14 allosterically activates several enzymatic processes that enhances ATPase activity and DUB activities, resulting in an increase in specificity for ubiquitin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Superimposition of USP14 -IU1 with USP14-Ubal demonstrated that IU1 inhibits USP14 by blocking the entrance of the ubiquitin C-terminus into the thumb-palm cleft where the catalytic center is buried (Figure 4A) (Wang et al., 2018)."

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"It appears that POH1 cleaves at the base of the ubiquitin chain where it is linked to the target protein, whereas USP14 and UCHL5 mediate a stepwise removal of ubiquitin from the protein by disassembling the chain from its distal tip [XREF_BIBR]."

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"Pharmacological inhibition of USP14 with IU1 increased ubiquitin turnover but did not affect cellular growth or morphology."

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"RPN11 and POH1 has been demonstrated to cleave at the base of the ubiquitin chain, removing ubiquitin en masse, while UCH37 and USP14 mediate a stepwise removal of ubiquitin from the substrate starting from the distal end."

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"This observation is extended in mammalian studies in which a mouse line with a loss-of-function mutation in Usp14, the mammalian homolog of Ubp6, reduces the free ubiquitin pool in neurons and results in ataxia that can be rescued with exogenous ubiquitin expression [63]."

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"Pharmacologic inhibition of USP14 with IU1 enhances ubiquitin turnover without inhibiting cell proliferation."

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"USP14 prevents proteasomal degradation of ubiquitin."

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"By separating ubiquitin from its conjugative target, Usp14 antagonizes this pathway of ubiquitin degradation."

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"In yeast and mammals, loss of USP14 and Ubp6 results in increased degradation of ubiquitin and decreased levels of monomeric Ub, suggesting that one function of USP14 is to recycle ubiquitin at the proteasome [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."

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"Importantly, neuron specific expression of Usp14 also restored cellular monomeric ubiquitin to wild type levels, confirming the role of this proteasome associated DUB in governing ubiquitin homeostasis and supporting a presynaptic role for USP14 in the ataxia phenotype of the ax J mice [XREF_BIBR, XREF_BIBR]."

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"Lee et al. conducted preclinical study to test whether the small molecule inhibitor of USP14, IU1, could inhibit the trimming of ubiquitin chains by the proteasome and whether IU1 could enhance proteasome function in cells (96)."

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"However, as UCHL5 and USP14 are proposed to mediate a stepwise removal of ubiquitin from the substrate by trimming the chain from its distal tip, this leaves the opportunity for MGRN1 to reach a monou[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"In the UbAl bound form of Usp14, BL1 and BL2 are displaced, allowing the ubiquitin C-terminus access to the binding groove [71]."

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"The western blot results showed that inhibition of both UCHL5 and USP14 by b-AP15 significantly increased the accumulation of polyubiquitinated proteins by 31.80 +/- 6.25% (P = 0.008, n = 5) and reduc[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"USP14 can rescue proteins from degradation by disassembling the ubiquitin chain from its substrate’s distal end ."

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"RPN11 appears to cleave at the base of the ubiquitin chain, where it is linked to the substrate, whereas USP14 and UCHL5 are known to mediate stepwise removal of ubiquitin from the substrate by disassembling the chain from its distal end [XREF_BIBR]."

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"RPN11 cleaves at the base of the ubiquitin chain where it is linked to the substrate, whereas UCH37 and apparently USP14 mediate a stepwise removal of ubiquitin from the substrate by disassembling the chain from its distal tip."

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"Here we show that Usp14, a proteasome associated deubiquitinating enzyme, can inhibit the degradation of ubiquitin protein conjugates, in vivo and in vitro."

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"Accordingly, USP14 and Ubp6 efficiently trim polyubiquitin chains attached to target proteins, thereby promoting the recycling of ubiquitin molecules."

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"By releasing ubiquitin molecules from the substrate, USP14 and Ubp6 helps to prevent the rapid degradation of ubiquitin molecules together with the substrate protein."

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"By regulating ubiquitin pools at the nerve terminal, Usp14 would therefore be able to modulate ubiquitin dependent processes required during synaptic development."