IndraLab

Statements


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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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"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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"These results strongly suggest that inhibition of USP14 by RNA aptamers might antagonize Ub chain-trimming on proteasomes, consequently facilitating the degradation of many UPS substrates.We investigated the effects of USP14 aptamers on HeLa cell viability."

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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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"Here we show that USP14, a proteasome associated deubiquitinating enzyme, can inhibit the degradation of ubiquitin protein conjugates both in vitro and in cells."

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"USP14 prevents proteasomal degradation of ubiquitin."

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

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

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