IndraLab

Statements

WDR48 activates USP46. 27 / 27
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"WDR48 stimulates the activity of the deubiquitylases USP1, USP12 and USP46."
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"USP12 and USP46, consisting of only a USP domain [4], share 88% amino acid sequence homology and are potentiated by WDR48, WDR20, and DMWD [8, 9, 10]."
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"For example, USP1, USP12, and USP46 are activated by the WD40-repeat containing UAF1, and USP7 is activated by GMPS (Cohn et al., 2007, 2009; Faesen et al., 2011; van der Knaap et al., 2005)."
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"This study confirmed that the modulator UAF1 activates USP1, USP12, and USP46, and GMPS activates USP7."
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"Together, UAF1 and WDR20 are able to synergistically stimulate the enzymatic activities of USP12 and USP46 to a peak level."
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"WDR48, with the high score in our LC-MS/MS results, is reported as a cofactor to increase the enzymatic activity of USP1, USP12 and USP46, but could not modify the affinity of the DUBs and their subst[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Therefore, this suggests that for some USPs the KG FP reagent may be a better substrate, and provide more relevant kinetic parameters.This study confirmed that the modulator UAF1 activates USP1, USP12[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"However, a structural comparison of the enzyme in these two post-reaction forms revealed few conformational differences, leaving the mechanism of USP46 activation by UAF1 elusive."
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"WDR48 stimulates the activity of three DUBs, USP12, USP46 and USP1, a DUB which regulates the Fanconi anemia DNA damage pathway."
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"Given the distinct binding mode elucidated here, it is less straightforward to reconcile this structure with direct active-site modulation, yet we propose a mechanism centered on WDR48 dependent USP s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Since UAF1 stimulates the deubiquitinating activity of USP1 and USP46 [XREF_BIBR, XREF_BIBR], we speculate that UAF1 and ubiquitin can simultaneously bind to opposite surfaces of the Fingers sub-domain in these DUBs."
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"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
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"Both WDR48 and WDR20 stimulate USP12 and USP46 catalytic activity (k cat) without increasing substrate binding affinity, suggesting that the WDR proteins may affect DUB activity via a novel structural mechanism."
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"WDR20 and UAF1 potentiate the activity of USP12 and USP46 by allosterically increasing their catalytic efficiency without increasing their substrate-binding affinity ."
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"However, as shown previously for USP46/UAF1 ( xref ), the combination of these complementary mutants rescues the activation ( xref f), highlighting the importance of the fingers sub domain in USP12 and USP46 ( xref ) activation by UAF1."
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"However, a structural comparison of the enzyme in these two post-reaction forms revealed few conformational differences, leaving the mechanism of USP46 activation by UAF1 elusive."
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"Two closely related DUBs, USP12 and USP46, are similarly activated by UAF-1, but unlike USP1, these can be hyperactivated by another WD40 repeat protein, named WDR20 [52–54] ."
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"In addition, whereas USP1 cannot interact with WDR20, USP12, and USP46 may; further WDR48 and WDR20 can both independently and cooperatively stimulate the activities of USP12 and USP46."
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"These findings raised the possibility that, like their yeast counterparts, human UAF1 and WDR20 might modulate subcellular localization of USP12 and USP46 and, furthermore, that cofactor binding might[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Although mammalian USP46 and USP12 DUB activity can be stimulated by two proteins UAF-1 and WDR20, the C. elegans homologs of these genes have not yet been identified."
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"Interestingly, the Caenorhabditis elegans homologs of WDR20 and WDR48 (also known as UAF1) can bind to and activate USP46."
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"UAF1 stimulates not only USP1, but also two other DUB enzymes, USP12 and USP46."
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"WDR48 and UAF1 is an activator of USP1 and more recently has been shown to activate USP12 and USP46."
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"Interestingly, USP12 and USP46 are activated by two β-propeller proteins, UAF1, and WDR20."
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"We found that increased expression of WDR-48, but not WDR-20, promotes USP-46 abundance in mammalian cells in culture and in C. elegans neurons in vivo Inhibition of the proteasome increased USP-46 abundance, and this effect was non additive with increased WDR-48 expression."
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"We found that USP-46 is ubiquitinated and that expression of WDR-48 reduces the levels of ubiquitin-USP-46 conjugates and increases the half-life of USP-46."
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"Interestingly, USP12 and USP46 are activated by two β-propeller proteins, UAF1, and WDR20."
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