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USP7 deubiquitinates REST. 11 / 12
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"We hypothesized that HAUSP functions as a critical counterbalance to beta-TrCP to inhibit REST ubiquitination and maintain NPCs."
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"Wt-HAUSP specifically counteracted beta-TrCP-mediated REST ubiquitination, while the Mt-HAUSP or the control deubiquitinase USP1 did not alter the REST ubiquitination (XREF_FIG), suggesting that HAUSP directly and specifically deubiquitinated REST and suppressed REST ubiquitination."
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"Thus, we have identified the consensus HAUSP binding site (310-PYSS-313) on human REST that is required for the HAUSP mediated REST deubiquitination."
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"We determined that HAUSP physically interacts with REST as demonstrated in co-immunoprecipitation assays (XREF_FIG; XREF_SUPPLEMENTARY), suggesting that HAUSP may mediate REST deubiquitination to prevent REST proteosomal degradation."
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"Normally, USP7 can deubiquitinate and stabilise the repressor element 1-silencing transcription factor (REST) at a post-transcriptional level and maintain the neural progenitor cells [ 52 ]."
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"Collectively, these data demonstrate that HAUSP negatively regulates REST ubiquitination and promotes REST stabilization."
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"HAUSP knockdown increased REST poly-ubiquitination as demonstrated by both anti-REST immunoprecipitation (IP) and anti-Ubiquitin reciprocal IP (XREF_FIG; XREF_SUPPLEMENTARY)."
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"HAUSP deubiquitinates REST to promote neural progenitor cell maintenance as discussed earlier."
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"These data further support that REST deubiquitination is specifically mediated by HAUSP."
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"To further address whether REST deubiquitination is directly and specifically mediated by HAUSP, we performed an in vitro deubiquitination assay XREF_BIBR with purified wild-type HAUSP (Flag-Wt-HAUSP), catalytic dead mutant HAUSP (Flag-Mt-HAUSP), or a control deubiquitinase USP1 (Flag-USP1)."
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"Our data demonstrate that HAUSP directly deubiquitinates REST."
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