IndraLab

Statements


14 | 35 14

reach
"hUSP1 and hUAF1 shares similar mode of interaction with USP46 and UAF1 complex [XREF_BIBR]."

sparser
"Similar to USP1, human USP46 forms a complex with UAF1 and the activity of USP46 is stimulated by UAF1 ( xref )."

reach
"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

reach
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."

No evidence text available

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."

sparser
"In addition, WDR48 3X interaction with USP46 was partially restored by the USP46 E186K charge-reversal mutant."

reach
"This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs."

sparser
"This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs."

reach
"USP12 and USP46 exhibit the conserved USP fold structure comprised of Fingers, Palm and Thumb subdomains, with the catalytic triad of cysteine, histidine and aspartic acid, nestled in between the Palm and Thumb FIGURE 1 | Model of USP46 bound to WDR48 and WDR20."

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]"

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sparser
"The purified complex displayed a deubiquitinase activity similar to the USP46-UAF1 complex."

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reach
"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)."

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."

No evidence text available

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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."

reach
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB (Figures 2A and 2B) ."

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 )."

reach
"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)."

reach
"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."

No evidence text available

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reach
"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)."

sparser
"The crystal structures of USP1-UAF1 reveal plasticity in USP1 and key differences to USP12-UAF1 and USP46-UAF1, two related proteases."

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB (Figures 2A and 2B) ."

No evidence text available

reach
"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]."

No evidence text available

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."

No evidence text available

reach
"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]"

reach
"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."

reach
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity."

reach
"For example, WDR48 interacts with USP1, USP12, and USP46 to activate their DUB activity (Cohn et al., 2009; Yin et al., 2015)."

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]"

sparser
"Also an USP46 mutant, USP46-E186K, that cannot bind to UAF1 could still deubiqutinate Cdt2 in the presence of E6 ( xref , lane 6)."

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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."

sparser
"Mutation of residues involved in the WDR48:USP46 interaction abrogated both binding and deubiquitinase activity of the complex."

reach
"Intriguingly, we find that these structures resemble the USP46 and UAF1 complex structure, including the presence of the second binding site."

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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."

reach
"The USP12 and UAF1 and USP46 and UAF1 complex can be further activated by binding to a second WD repeat protein, WDR20."

reach
"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."

reach
"UAF1 also interacts with DUBs USP12 and USP46 (Garcia-Santisteban et al., 2013) and, thus, both genes also could be involved in senescence."

reach
"In addition, WDR48 3X interaction with USP46 was partially restored by the USP46 E186K charge reversal mutant."

reach
"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)."

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."

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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."

reach
"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."

reach
"Figure 1: Model of USP46 bound to WDR48 and WDR20."

reach
"In the complex we find two potential sites for UAF1 binding, analogous to what was seen in a USP46 and UAF1 complex."

sparser
"We crystallized a ternary complex that included full-length WDR48 bound to the USP46 25–366 ∼ubiquitin conjugate."

reach
"This model is inferred from a combination of structures of USP46 bound to WDR48 and ubiquitin (Yin et al., 2015) and USP12 bound to WDR48 and WDR20 (Li et al., 2016)."

sparser
"WDR48 interacts with the USP46 fingers subdomain via a relatively small, highly polar surface on the top center of the WDR48 β propeller."

reach
"WDR48, a WD40 repeat containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity."

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)."

No evidence text available

reach
"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."