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WDR48 activates USP1. 52 / 58
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"In vitro, USP1 activity is greatly stimulated by USP1-associated factor 1 (UAF1; also known as WDR48), enhancing USP1 catalytic turnover (k ) but not affinity (K ) for monoubiquitylated substrates ."
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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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"UAF1 increases the basicity of the USP1 catalytic histidine, increasing its potency as a general base."
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"The activation of USP1 by UAF1 takes place through an allosteric mechanism where the catalytic turnover (k cat ) of the enzyme is increased several fold (Cohn et al , xref )."
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"For example, in contrast to the USP46 BL1 residue F258, which supports the tail of Ub, the corresponding USP12 residue F262 is pushed into the catalytic cleft and would collide with the substrate.Usin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Its phosphorylation at Ser313 is essential for interacting with UAF1 and subsequent stimulation of USP1 activity [XREF_BIBR]."
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"Mutation of Ser313 to Ala on USP1 abolished the complex formation between USP1 and UAF1, thus prevented the activation of USP1 by UAF1( xref )."
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"Previous work on UAF1-USP1 binding showed WD40 domain of UAF1 was sufficient to act as an adapter protein and activate the catalytic DUB activity of USP1, which on its own has very little intrinsic catalytic activity in-vitro ."
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"In vitro, USP1 activity is greatly stimulated by USP1-associated factor 1 (UAF1; also known as WDR48), enhancing USP1 catalytic turnover (k cat ) but not affinity (K m ) for monoubiquitylated substrates 74 ."
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"Using ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) as a substrate, we have previously shown that UAF1 activates USP1 mainly by increasing its catalytic turnover (k), instead of its affinity toward the [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This is in accord with our previous finding that UAF1 stimulates the catalytic activity of USP1 allosterically by modulating the USP1 active site."
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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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"It is conceivable that the association of UAF1 with USP1 mask the the APC/C Cdh1 degron, thus promoting the stability of USP1."
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"It should be noted that USP1 forms a stable complex with UAF1, which stimulates the catalytic activity of USP1 [112]."
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"Although the molecular basis for UAF1 mediated USP1 activation remains to be fully understood, recent in vitro analyses using artificial substrates support an allosteric mechanism, involving UAF1 induced conformational changes in the USP1 active site [XREF_BIBR]."
23937906
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"Using ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) as a substrate, we have previously shown that UAF1 activates USP1 mainly by increasing its catalytic turnover (k cat), instead of its affinity toward the substrate (K M)."
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"Usp1 is the physiologically relevant deubiquitinating enzyme for PCNA-Ub and is activated by UAF1."
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"In vitro , USP1 activity is greatly stimulated by USP1-associated factor 1 ( UAF1 ; also known as WDR48 ) , enhancing USP1 catalytic turnover ( kcat ) but not affinity ( Km ) for monoubiquitylated substrates74 ."
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"Mechanistically, UAF1 increases the catalytic turnover (k cat), but does not increase the affinity of USP1 for its substrate (K M)."
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"A noncanonical cysteine protease USP1 is activated through active site modulation by USP1 associated factor 1."
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"13 , 16 , 17 In general, USP1 and WDR48 form a complex and function together, and WDR48 significantly enhances USP1 activity by stabilizing its expression and mediating its access to substrates."
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"We previously reported that UAF1 stimulates the catalytic activity of USP1 through an allosteric mechanism by modulating the USP1 active site."
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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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"By probing the active site residues we revealed that the USP1 active site can be modulated by the binding of UAF1."
23797609
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"Our study also revealed the molecular basis for the activation of USP1 by UAF1."
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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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"S2) and found that UAF1 predominantly activates the catalytic turnover (k cat) of Usp1, without a significant effect on the affinity (K m) for PCNA-Ub."
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"This observation indicates that UAF1 activates the DUB enzyme activity of USP1 and that it functions as a scaffolding protein for USP1 targeting FANCD2 [XREF_BIBR, XREF_BIBR]."
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"UAF1 stimulates not only USP1, but also two other DUB enzymes, USP12 and USP46."
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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 (Cohn et al., 2007, 2009; Faesen et al., 2011)."
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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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"Mutation of Ser313 to Ala on USP1 abolished the complex formation between USP1 and UAF1, thus prevented the activation of USP1 by UAF1."
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"Although ATAD5 depletion does not alter protein levels of USP1 [XREF_BIBR], since UAF1 increases USP1 activity [XREF_BIBR], it is still possible that ATAD5 regulates deubiquitination activity of USP1 through UAF1."
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"Our results support a regulatory mechanism in which UAF1 activates USP1 by modulating its active site conformation."
22439892
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"Using probes specific for the cysteine catalytic triad residues, we recently showed that UAF1 activates USP1 by modulating its active site conformation( xref )."
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"However, our data suggest that one of the primary mechanisms by which USP1 is activated by UAF1 is through relieving the auto‐inhibition caused by the joint action of inserts L1 and L3."
33619839
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"We performed a preliminary estimation of the Michaelis-Menten kinetics of the reaction, using a single time point assay () and found that UAF1 predominantly activates the catalytic turnover ( k cat ) of Usp1, without a significant effect on the affinity (K m ) for PCNA-Ub."
22989887
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"Our study also revealed the molecular basis for the activation of USP1 by UAF1."
22439892
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"The first of these pathways acts directly on the enzymatic activity of USP1, which is stimulated by binding to a co-factor, USP1 associated factor 1 (UAF1), also known as WDR48."
22744751
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"Using ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) as a substrate, we have previously shown that UAF1 activates USP1 mainly by increasing its catalytic turnover (k cat ), instead of its affinity toward the substrate (K M ) ( xref )."
27373336
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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 (Cohn et al., 2007 (Cohn et al., , 2009 Faesen et al., 2011) ."
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"It has been shown that UAF1 activates USP1 through a potential active-site modulation, and the complex formation between USP1 and UAF1 is regulated by serine phosphorylation."
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"USP1 (ubiquitin specific peptidase 1), which promotes de-ubiquitination of mono-ubiquitinated PCNA [57], forms a stable complex with UAF1 (USP1 associated factor 1), which stabilizes and activates USP[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Notable examples include USP7 activation by its HUBL domain and GMPS ( xref ), USP1 activation by UAF1 ( xref ), and Ubp8 activation in the SAGA complex ( xref )."
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"Human USP1 is stimulated by a WD40-repeat protein UAF1 (USP1 associated factor 1) through the formation of a stable complex."
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"The WD-repeat protein WDR48 (USP1 associated factor UAF-1) stimulates activity of ubiquitin specific proteases USP1, USP12, and USP46."
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"It has been shown that UAF1 activates USP1 through a potential active-site modulation, and the complex formation between USP1 and UAF1 is regulated by serine phosphorylation."
23797609
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"Notable examples include USP7 activation by its HUBL domain and GMPS, USP1 activation by UAF1, and Ubp8 activation in the SAGA complex."
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"Interestingly, UAF1 and WDR48 can fully activate the DUB activity of USP1, which regulates the Fanconi anemia DNA repair pathway [XREF_BIBR], but only weakly stimulates the catalytic activity of USP46 and USP12 [XREF_BIBR, XREF_BIBR, XREF_BIBR], whereas full activation of USP12 requires ternary complex formation with both UAF-1 and WDR48 and WDR20 [XREF_BIBR]."
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"By using a fluorescent ubiquitin derivative Ub-AMC, Cohn et al demonstrated that UAF1 does not increase the affinity of USP1 for Ub-AMC, but robustly increases its catalytic rate."
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"WDR48 (also known as USP1 associated factor 1, UAF-1) stimulates the activity of USP1 (Cohn et al., 2007) as well as that of two smaller homologs, USP12 and USP46 (Cohn et al., 2009)."
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"This study confirmed that the modulator UAF1 activates USP1, USP12, and USP46, and GMPS activates USP7."
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