IndraLab

Statements

USP20 is phosphorylated on S333. 50 / 50
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"Taken together, these data suggest that phosphorylation of USP20 on Ser334 augments SMC proliferation and migration, particularly to agonists distinct from PDGF, like IL-1β."
37311534
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"Preventing USP20 phosphorylation on Ser334 augments association with and deubiquitination of TRAF6."
37311534
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"To understand mechanisms by which phosphorylation of USP20 on Ser334 may regulate SMC and vascular inflammation, we first asked whether USP20-S334A retains a WT level of ubiquitin-binding activity—because substrate binding is the rate-limiting step in DUB activity ( xref )."
37311534
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"Thus, it seems that preventing USP20 phosphorylation on Ser334 augments the association of USP20 with its intracellular substrate TRAF6, even though it has no effect on the association of USP20 with the idealized substrate Ub-VME ( xref , A and B )."
37311534
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"Recent studies have shown that β 2 AR activation triggers site-specific phosphorylation of USP20 by the cAMP-activated protein kinase A (PKA) at serine 333 of USP20 [ xref ]."
28137506
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"Next, we performed the proteome profiler assay using the proteins extracted from sprouted aortic rings of USP20-S334D and congenic WT ( xref , xref ) in order to identify specific angiogenic factors regulated by S334 phosphorylation of USP20."
40475497
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"Reversible phosphorylation of USP20 at S333 could be a critical factor that determines the rate of down-regulation of β 2 ARs via autophagosomes during catecholamine stress [ xref ]."
28137506
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"Residing within the motif RMKDRKF S 334 WGQQRTN, the Ser334 of USP20 is phosphorylated by PKAα—even though the amino acid sequence slightly diverges from the canonical RRxS PKA motif ( xref , xref )."
37311534
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"Phosphorylation of human USP20 on Ser333 in the absence of purified kinase was attributed to the activity of one or more kinases in the COS-7 cells."
37311534
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"We conclude that USP20 expression inversely correlates with the extent of angiogenesis, and that inhibiting USP20 Ser334 phosphorylation could be a useful strategy to constrain inflammation-driven angiogenesis under pathological circumstances, like cancer and atherosclerosis."
40475497
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"Furthermore, we have seen in xref and xref that preventing phosphorylation of USP20 on Ser334 reduces TRAF6 ubiquitination and NFκB activity."
37311534
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"Together, these results suggest that IRAK1 inhibits USP20-mediated deubiquitination of TRAF6 by phosphorylating USP20 on Ser334 and reducing USP20:TRAF6 association."
37311534
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"It therefore seems likely that IL1-β-induced inflammatory signaling can be suppressed by preventing USP20 phosphorylation on Ser334."
37311534
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"This work demonstrates that blocking phosphorylation of USP20 on Ser334 augments the anti-inflammatory activity of USP20 on IL-1β signaling ( xref )."
37311534
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"In preparations of purified proteins and in intact SMCs, we found that phosphorylation of USP20 on Ser334 is mediated by IRAK1."
37311534
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"Thus, IRAK1 not only transduces IL-1R signaling ( xref ) but also prevents its termination: phosphorylation of USP20 on Ser334 reduces USP20’s binding to TRAF6 and thereby diminishes (a) USP20-mediated deubiquitination/deactivation of TRAF6 and (b) consequent attenuation of downstream NFκB activation."
37311534
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"The Ser334 phosphorylation status of USP20 affects neither the binding of USP20 to the active-site directed probe Ub-VME nor USP20-mediated deubiquitination per se : whereas phosphorylation of USP20 on Ser334 reduces USP20-mediated deubiquitination of the β 2 -adrenergic receptor, it increases USP20-mediated deubiquitination of the β 1 -adrenergic receptor ( xref , xref )."
37311534
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"USP20 Serine334 phosphorylation increases NFκB signaling in ECs."
40475497
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"Thus, a reduction in USP20 expression and activity or an increase in USP20 S334 phosphorylation as seen in human atherogenic samples xref , xref can engender an increase in NFκB signaling, as well as angiogenic growth leading to neo vessel formation in an atherosclerotic plaque."
40475497
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"These apparently paradoxical results may be reconciled by considering the regulatory role played by phosphorylating USP20 on Ser334."
37311534
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"Phosphorylation of USP20 on Ser334 substantially attenuates the anti-inflammatory activity of USP20-WT, whether USP20-WT expression is physiologic or supraphysiologic."
37311534
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"Antagonizing USP20 with a dominant-negative mutant vitiates the anti-inflammatory activity of USP20, but preventing phosphorylation of USP20 on Ser334 augments the anti-inflammatory activity of USP20."
37311534
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"Whether targeting USP20-Ser334 phosphorylation therapeutically could mitigate inflammatory vascular diseases like atherosclerosis remains an intriguing possibility."
37311534
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"In this process, phosphorylation of USP20 at serine residue 333 is required for its activity providing an additional level of regulation [ xref ]."
30126257
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"The association of USP20 with its substrates triggers deubiquitinase activity; this association is regulated by phosphorylation of USP20 on Ser334 (mouse) or Ser333 (human)."
37311534
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"The association of USP20 with its substrates triggers deubiquitinase activity; this association is regulated by phosphorylation of USP20 on Ser334 (mouse) or Ser333 (human)."
37311534
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"USP20 Ser333 phosphorylation was greater in SMCs of atherosclerotic segments of human arteries as compared with nonatherosclerotic segments."
37311534
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"To determine whether USP20 Ser334 phosphorylation regulates proinflammatory signaling, we created USP20-S334A mice using CRISPR/Cas9-mediated gene editing."
37311534
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"WT carotid SMCs showed substantial phosphorylation of USP20 Ser334, and WT carotids demonstrated greater NFκB activation, VCAM-1 expression, and SMC proliferation than USP20-S334A carotids."
37311534
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"We now demonstrate a novel role for USP20 Serine334 phosphorylation in angiogenesis."
40475497
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"Our findings reveal novel mechanisms regulating IL-1β-induced proinflammatory signaling: by phosphorylating USP20 Ser334, IRAK1 diminishes the association of USP20 with TRAF6 and thus augments NFκB activation, SMC inflammation, and neointimal hyperplasia."
37311534
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"Phosphorylation of USP20 on Ser334, for example, augments both the association of USP20 with the β 1 -adrenergic receptor and USP20’s deubiquitination of the β 1 -adrenergic receptor ( xref , xref )."
37311534
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"In contrast, phosphorylation of USP20 Ser334 reduces both the association of USP20 with the β 2 -adrenergic receptor and USP20’s deubiquitination of the β 2 -adrenergic receptor ( xref , xref )."
37311534
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"Nonetheless, the intrinsic DUB activity of USP20 is not changed by phosphorylation of USP20 on Ser334 ( xref )."
37311534
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"To determine whether and how phosphorylation of USP20 on Ser334 affects TRAF6 deubiquitination and NFκB activation in SMCs, we employed gene-edited mice expressing a S334A mutant version of USP20."
37311534
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"USP20 is phosphorylated on Ser333 in SMCs of atherosclerotic human arteries."
37311534
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"To discern whether USP20 Ser333 phosphorylation could be relevant in human atherosclerosis, we used IgG specific for phospho-USP20(Ser333) ( xref ) to immunostain atherosclerotic human arteries obtained from legs that had been amputated because of arterial insufficiency ( xref )."
37311534
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"Thus, arterial inflammation inherent in atherosclerosis correlates with phosphorylation of USP20 on its regulatory residue Ser333."
37311534
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"Preventing USP20 phosphorylation on Ser334 attenuates vascular inflammation."
37311534
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"To investigate the role of USP20 Ser334 phosphorylation in vivo , we used a CRISPR/Cas9 ( xref ) strategy to create a mouse expressing a USP20 mutant that harbors Ala instead of Ser at residue 334 (USP20-S334A, xref )."
37311534
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"To determine whether SMC USP20 Ser334 phosphorylation modulates vascular inflammation in vivo , we subjected USP20-S334A and WT littermate mice to carotid endothelial denudation."
37311534
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"Did phosphorylation of USP20 on Ser334 occur during neointimal hyperplasia?"
37311534
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"Phosphorylation of USP20 on Ser334 could not be detected in mouse carotid arteries prior to endothelial denudation—even though USP20 itself was easily detectable ( xref , A and C ) ."
37311534
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"However, in the context of arterial inflammation associated with neointimal hyperplasia, phosphorylation of USP20 on Ser334 clearly manifested ( xref , B and D )."
37311534
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"As expected ( xref , xref ), no phosphorylation of USP20 on Ser334 was detectable in either native or injured arteries of the USP20-S334A mouse ( xref )."
37311534
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"Altogether, these findings and xref suggest that phosphorylation of USP20 on Ser334 augments neointimal hyperplasia primarily by increasing inflammatory signaling and associated proliferation of SMCs."
37311534
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"Thus, phosphorylation of USP20 on Ser334 occurs during atherogenesis in human arteries and during nonatherosclerotic neointimal hyperplasia in mouse arteries."
37311534
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"These data suggest that preventing USP20 Ser334 phosphorylation reduces NFκB activation in the context of neointimal hyperplasia."
37311534
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"β1AR-induced phosphorylation of USP20 Ser333 by protein kinase A-α (PKAα) was required for optimal USP20-mediated regulation of β1AR lysosomal trafficking."
30538132
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"Accordingly, we conclude that USP20 activity in ECs negatively regulates NFκB signaling, whereas USP20 S334 phosphorylation promotes NFκB signaling."
40475497