IndraLab

Statements

USP46 binds WDR48. 54 / 73
19 | 37 17
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"Intriguingly, we find that these structures resemble the USP46 and UAF1 complex structure, including the presence of the second binding site."
27650958
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"We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the DUB to deubiquitinate and stabilize GLR-1 in vivo."
24356955
sparser
"Similar to USP1, human USP46 forms a complex with UAF1 and the activity of USP46 is stimulated by UAF1 ( xref )."
22118673
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"The scaffold protein UAF1 forms a complex with USP1, USP12, and USP46 that is essential for their activity."
36798153
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"UAF1 also binds and activates two other DUBs, USP12 and USP46 (19), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner (20, 21)."
30456385
sparser
"This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs."
25744535
sparser
"The USP46-WDR48 interface and the USP46-WDR48-Ub complex share nearly the same characteristics. xref The interface between USP46 and WDR20 is facilitated through both hydrophobic and hydrophilic contacts."
39410943
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"This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs."
25744535
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"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
23797609
sparser
"The high affinity binding could be partially rescued by combining the USP12 E190K with the UAF1 3X mutant, in a similar fashion to what was observed for USP46 and UAF1 binding ( xref c) ( xref )."
27650958
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"Fifty percent of inhibition of the closely related USP12–UAF1 and USP46–UAF1 complexes only occurred at 10 μmol/L compared with USP1-UAF1 IC of 4.1 nmol/L, reflecting a >2,000-fold selectivity.Next, we assessed on-target activity of I-138 using USP1 isogenic HAP-1 cells."
36228090
sparser
"Also an USP46 mutant, USP46-E186K, that cannot bind to UAF1 could still deubiqutinate Cdt2 in the presence of E6 ( xref , lane 6)."
30415951
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"In addition, WDR48 3X interaction with USP46 was partially restored by the USP46 E186K charge reversal mutant."
26388029
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"hUSP1 and hUAF1 shares similar mode of interaction with USP46 and UAF1 complex [XREF_BIBR]."
29091922
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"In the context of such multiprotein complexes, this recruitment and orientation of substrate may contribute to more efficient catalysis in addition to the stimulation provided by the beta-propeller in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26388029
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"The three-dimensional structure of USP1 and USP46 have not yet been solved, but in silico modeling using the structure of USP7 catalytic domain [XREF_BIBR] as a template indicates that USP1 (420-520) and USP46 (165-259) UAF1 binding motifs lie within their Fingers sub-domain."
25744535
reach
"The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans."
24356955
sparser
"In addition, WDR48 3X interaction with USP46 was partially restored by the USP46 E186K charge-reversal mutant."
26388029
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"Reciprocal IP-MS/MS suggests the existence of multiple distinct Dub complexes in which USP12 (or USP46) interacts with WDR48, WDR20 (or DMWD), and PHLPP (or PHLPPL) (XREF_FIG, XREF_SUPPLEMENTARY)."
19615732
sparser
"The purified complex displayed a deubiquitinase activity similar to the USP46-UAF1 complex."
35008200
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"Intriguingly the same crystal packing was seen for the USP46 and UAF1 complex (PDB code : 5CVN) that was published during the refinement of our structures."
27650958
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"Pimozide showed biochemical selectivity against USP2, USP5, USP7, USP8, and the USP46–UAF1 complex, in addition to the UCH DUBs UCHL1 and UCHL3, and the ubiquitin-like protease SENP1 (sentrin-specific[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24717260
sparser
"The activity of purified E6-USP46 complex was 0.78 FU/min compared to 0.83 FU/min for USP46-UAF1 complex ( xref C)."
35008200
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"The high affinity binding could be partially rescued by combining the USP12 E190K with the UAF1 3X mutant, in a similar fashion to what was observed for USP46 and UAF1 binding (XREF_FIG c)."
27650958
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"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1 associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [XREF_BIBR]."
29386062
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"Additionally, the study also found out that the UAF1/USP12 and UAF1/USP46 complexes increase p65 expression, which promotes NF-κB activation and increases NLRP3 and IL-1β expression levels."
| PMC
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"UAF1 also interacts with DUBs USP12 and USP46 (Garcia-Santisteban et al., 2013) and, thus, both genes also could be involved in senescence."
27160904
sparser
"On the other hand, whether the promotional or inhibitory effects exerted by USP12 in different diseases and immune responses require its deubiquitinating enzyme activity or the binding of the cofactor like USP46 or WDR48, and the specific mechanisms still need to be studied in greater depth."
37752518
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"The scaffold protein UAF1 forms a complex with USP1, USP12, and USP46 that is essential for their activity."
37289831
sparser
"We crystallized a ternary complex that included full-length WDR48 bound to the USP46 25–366 ∼ubiquitin conjugate."
26388029
reach
"In this regard, it has been reported that, besides USP1, UAF1 also binds and regulates the activity of two other DUBs, namely USP12 and USP46 XREF_BIBR."
22701671
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"It is tempting to speculate that nuclear relocation of the USP12 and UAF1 and USP46 and UAF1 complexes could be mediated by, as yet unidentified, NLSs in the DUBs."
22701671
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"In addition, the UAF1 and USP12 and UAF1 and USP46 complexes promote NF-kappaB activation, enhance the transcription of NLRP3 and proinflammatory cytokines (including pro-IL-1beta, TNF, and IL-6) by inhibiting ubiquitination mediated degradation of p65."
33247121
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"USP1-associated factor 1 (UAF1), which is also called WD repeat-containing protein 48, can bind USP1, USP12, and USP46 and stimulate the activity of these ubiquitin-specific proteases (USPs) (6)."
36988464
sparser
"The crystal structures of USP1-UAF1 reveal plasticity in USP1 and key differences to USP12-UAF1 and USP46-UAF1, two related proteases."
33795880
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"Notably, ML323 did not inhibit the USP46 and UAF1 complex that contains the same UAF1 subunit as the USP1 and UAF1 complex and demonstrated little inhibition against USP1 alone (IC 50> 200 muM) in a Ub-Rho assay in which USP1-UAF1 and USP1 demonstrated similar K m values."
24531842
sparser
"Researchers found that ML323, which is a novel NLRP3 inflammatory microsome inhibitor, can specifically inhibit the UAF1/USP1 but not the UAF1-USP12 and UAF1-USP46 complexes [ xref , xref ]."
37752518
reach
"UAF1/USP12 and UAF1/USP46 complexes promote NF-κB activation and enhance the transcription of NLRP3 and proinflammatory cytokines (9)."
36988464
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"The USP46-WDR48 interface and the USP46-WDR48-Ub complex share nearly the same characteristics."
39410943
reach
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity."
27880911
sparser
"Pimozide showed biochemical selectivity against USP2, USP5, USP7, USP8, and the USP46–UAF1 complex, in addition to the UCH DUBs UCHL1 and UCHL3, and the ubiquitin-like protease SENP1 (sentrin-specific[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24717260
reach
"Recent structural insights into the USP46 and UAF1 complex and the USP12, UAF1, and WDR20 complex revealed that the activators interact with surfaces remote from the catalytic center and mediate activation via long-range allosteric mechanisms."
27591049
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"In the complex we find two potential sites for UAF1 binding, analogous to what was seen in a USP46 and UAF1 complex."
27650958
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"WDR48, a WD40 repeat containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity."
21183687
sparser
"In addition to activating USP1 [ 11 ], largely through an increase in k cat , UAF1 activates other DUBs in distinct complexes, such as UAF1-USP12-WDR20 and UAF1-USP46 [ 19,20 ]."
23962487
sparser
"We then used the linear relationship between k obs and S170Y concentration to determine k on and k off , and thus K D . A similar kinetic analysis was employed to quantify the weak interaction b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26388029
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"Reminiscent of the Ub bound UAF1 and USP46 complex, the UAF1-USP12 structure features an L shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme (XREF_FIG and XREF_FIG)."
27373336
sparser
"Complexes of USP46 and WDR48 were formed by incubating the proteins at 400 nM USP46 and either 400 nM or 8,000 nM WDR48 overnight at 4°C. Complexes were then mixed 1:1 with serial dilutions of Ub-AMC [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26388029
reach
"Mechanistically, USP46 can bind with WD40-repeat (WDR) proteins WDR-20 and WDR-48 to stimulate USP46 catalytic activity and increase GLR-1 levels."
26528125
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"Together, these results support a model in which WDR-48 binds and stabilizes USP-46 protein levels by preventing the ubiquitination and degradation of USP-46 in the proteasome."
32587090
sparser
"Fifty percent of inhibition of the closely related USP12–UAF1 and USP46–UAF1 complexes only occurred at 10 μmol/L compared with USP1-UAF1 IC 50 of 4.1 nmol/L, reflecting a >2,000-fold selectivity."
36228090
reach
"For example, UAF1/USP12 and UAF1/USP46 complexes promote NF-κB activation and enhance the transcription of NLRP3 and pro-IL-1β by inhibiting ubiquitin-mediated degradation of p65 [81]."
36148948
reach
"The USP12 and UAF1 and USP46 and UAF1 complex can be further activated by binding to a second WD repeat protein, WDR20."
27650958
reach
"In C. elegans, USP46 and USP12 both bind to USP1 associated factor 1 (UAF1 and WDR48) and the binding dramatically enhances the activity of USP12 and USP46."
26077708