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WDR20 activates USP12. 55 / 58
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"To investigate the mechanism by which WDR20 activates USP12 , we next determined the crystal structure of a ternary complex consisting of USP12 , UAF1 lacking its SLD , and WDR20 at a 3 ."
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"In agreement with our enzyme kinetics data, our binding studies revealed negligible changes in the substrate binding affinity of USP12 induced by UAF1 or WDR20 (XREF_FIG and XREF_SUPPLEMENTARY)."
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"In agreement with our enzyme kinetics data, our binding studies revealed negligible changes in the substrate binding affinity of USP12 induced by UAF1 or WDR20 (Figures 6A and S6) ."
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"Overall, our two UAF1-USP12 structures not only reveal a series of structural changes of the enzyme that are connected to the binding site of UAF1 but also highlight the dynamic nature of three key lo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Based on our result, we propose a tenable model for USP12 activation by UAF1 and WDR20 ( xref )."
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"USP12 and USP46, but not USP1, can be independently activated by another WD40-repeat-containing protein, WDR20 (Burska et al., 2013; Dahlberg and Juo, 2014; Kee et al., 2010; McClurg et al., 2014) ."
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"Mechanism of USP12 Activation by UAF1 and WDR20."
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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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"Based on our results, we propose a tenable model for USP12 activation by UAF1 and WDR20 (Figure 7) ."
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"Interestingly, USP12 and USP46 are activated by two β-propeller proteins, UAF1, and WDR20."
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"To investigate the mechanism by which WDR20 activates USP12, we next determined the crystal structure of a ternary complex consisting of USP12, UAF1 lacking its SLD, and WDR20 at a 3.0 Å resolution ()[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Based on our results , we propose a tenable model for USP12 activation by UAF1 and WDR20 ( Figure 7 ) ."
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"These results strongly suggest that WDR20 can activate USP12 by allosterically optimizing its catalytic cleft , whereas the effect of UAF1 binding cannot be directly transmitted to the catalytic cysteine through USP12 ."
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"Interestingly, USP12 and USP46 are activated by two β-propeller proteins, UAF1, and WDR20."
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"The human deubiquitinase, ubiquitin-specific peptidase 12 (uSP12), acts as a tumor suppressor and is catalytically activated by uSP1-associated factor 1 (uaF1) and Wdr20."
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"The distinct binding sites and synergistic effect of the two propeller proteins on USP12 raise the question of whether UAF1 and WDR20 activate USP12 via two independent or converging allosteric pathwa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This is a result of enhanced activity of the endogenous Usp12 complex caused by increased levels of WDR20 which supports our data on the positive feedback loop within this complex."
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"To investigate the mechanism by which WDR20 activates USP12, we next determined the crystal structure of a ternary complex consisting of USP12, UAF1 lacking its SLD, and WDR20 at 3.0 A resolution (XREF_SUPPLEMENTARY)."
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"These results suggest that, even though fine tuning the Ub globular domain-tail junction is not critical for WDR20 to activate USP12, interaction between BL1 and the Ub globular domain is still important for the full WDR20 stimulated USP12 activity."
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"The distinct binding sites and synergistic effect of the two propeller proteins on USP12 raises the question of whether UAF1 and WDR20 activate USP12 via two independent or converging allosteric pathways."
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"This result clearly indicates that UAF1 and WDR20 allosterically activate USP12 through two distinct pathways."
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"First , our results rule out the possibility that UAF1 and WDR20 activate USP12 by enhancing its substrate affinity ."
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"Nevertheless , the free USP12 structure alone is insufficient to link these predicted changes to USP12 activation by UAF1 or WDR20 ."
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"Ning Zheng (USA) presented molecular studies of USP12, revealing that UAF1 and WDR20 potentiate USP12 catalytic activity."
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"This result clearly indicates that UAF1 and WDR20 indeed allosterically activate USP12 through two distinct pathways."
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"To investigate the mechanism by which WDR20 activates USP12, we next determined the crystal structure of a ternary complex consisting of USP12, UAF1 lacking its SLD, and WDR20 at a 3.0 Å resolution (Table S1 )."
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"This result clearly indicates that UAF1 and WDR20 allosterically activate USP12 through two distinct pathways ."
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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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"This result clearly indicates that UAF1 and WDR20 allosterically activate USP12 through two distinct pathways."
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"These results strongly suggest that WDR20 can activate USP12 by allosterically optimizing its catalytic cleft, whereas the effect of UAF1 binding can not be directly transmitted to the catalytic cysteine through USP12."
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"USP12 can be further activated by WDR20 [ 179,180 ] ."
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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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"These results suggest that even though fine-tuning the Ub globular domain-tail junction is not critical for WDR20 to activate USP12 , interaction between BL1 and the Ub globular domain is still important for the full WDR20-stimulated USP12 activity ."
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"In agreement with our enzyme kinetics data, our binding studies revealed negligible changes in the substrate binding affinity of USP12 induced by UAF1 or WDR20."
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"In USP12, this loop is important for activation, as mutation of a stretch of glycine residues within the loop leads to loss in activation of USP12 by either UAF1 or WDR20."
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"To investigate the mechanism by which WDR20 activates USP12, we next determined the crystal structure of a ternary complex consisting of USP12, UAF1 lacking its SLD, and WDR20 at 3.0 Å resolution ( xref )."
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"To gain deeper mechanistic insights into USP12 activation by UAF1 and WDR20 , we first determined the steady-state kinetics of substrate hydrolysis by USP12 in different forms ."
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"USP12 and USP46, but not USP1, can be independently activated by another WD40-repeat-containing protein, WDR20 ()."
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"Neither was differentially methylated in our study, but several DMR genes mediate AR or its effects in various contexts in other species: hey2 (Fig. 1c), pkn1(102295574) and ncoa2, usp12, usp32 (Fig. 1b), and zmiz1(102310819) [84–88]."
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"To gain deeper mechanistic insights into USP12 activation by UAF1 and WDR20, we first determined the steady-state kinetics of substrate hydrolysis by USP12 in different forms."
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"The distinct binding sites and synergistic effect of the two propeller proteins on USP12 raises the question of whether UAF1 and WDR20 activate USP12 via two independent or converging allosteric pathways."
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"Nevertheless, the free USP12 structure alone is insufficient to link these predicted changes to USP12 activation by UAF1 or WDR20."
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"These results suggest that even though fine tuning the Ub globular domain-tail junction is not critical for WDR20 to activate USP12, interaction between BL1 and the Ub globular domain is still importa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"These results strongly suggest that WDR20 can activate USP12 by allosterically optimizing its catalytic cleft, whereas the effect of UAF1 binding cannot be directly transmitted to the catalytic cysteine through USP12."
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"USP12 can be further activated by WDR20 [ xref , xref ]."
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"First, our results rule out the possibility that UAF1 and WDR20 activate USP12 by enhancing its substrate affinity."
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"Without increasing substrate affinity, they most likely potentiate USP12 by promoting the step of nucleophilic attack by the catalytic cysteine.The distinct binding sites and synergistic effect of the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The free USP12 structure alone, nevertheless, is insufficient to link these predicted changes to USP12 activation by UAF1 or WDR20."
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"First, our results rule out the possibility that UAF1 and WDR20 activate USP12 by enhancing its substrate affinity."
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"These results suggest that, even though fine-tuning the Ub globular domain-tail junction is not critical for WDR20 to activate USP12, interaction between BL1 and the Ub globular domain is still important for the full WDR20-stimulated USP12 activity."
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"Based on our results, we propose a tenable model for USP12 activation by UAF1 and WDR20 ()."
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"This result clearly indicates that UAF1 and WDR20 indeed allosterically activate USP12 through two distinct pathways."
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"Overall, our two UAF1-USP12 structures not only reveal a series of structural changes of the enzyme that are connected to the binding site of UAF1 but also highlight the dynamic nature of three key loops, namely, BL2, BL3, and the CC Loop, surrounding the catalytic site of the activated enzyme.To investigate the mechanism by which WDR20 activates USP12, we next determined the crystal structure of a ternary complex consisting of USP12, UAF1 lacking its SLD, and WDR20 at a 3."
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"Finally, we show that both DMWD and WDR20 promote USP12 enzymatic activity, but they differentially modulate the subcellular localization of the DUB."
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"Uaf-1 and WDR20 have previously been shown to stimulate Usp12 catalytic activity [XREF_BIBR, XREF_BIBR]."
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