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Statements

USP20 is phosphorylated. 69 / 83
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"Therefore, the induction of HMGCR, p -USP20, and p -mTOR by re-feeding was partially prevented by EA, with no effect on the levels of total USP20 and mTOR (P > 0.05)."
37916105
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"Additionally, β1AR-induced USP20 phosphorylation may serve as a feed-forward mechanism to stabilize β1AR expression and signaling during pathological insults to the myocardium."
30538132
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"Inhibition of ATR by BAY1895344 or siRNA markedly decreased the phosphorylation of USP20 as well as its protein levels (Figures  xref and xref )."
38124786
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"We then examined whether ATR‐mediated USP20 phosphorylation affected its stabilization."
38124786
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"These suggest that ATR-mediated phosphorylation of USP20 promotes dissociation of USP20 from HERC2, and this dissociation would stabilize CLASPIN and promote CHK1 activation."
25326330
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"Upon feeding-induced activation of mTORC1, USP20 undergoes phosphorylation, leading to its interaction with gp78 and subsequent stabilization of HMGCR."
39551780
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"Similar to other DNA repair proteins, USP20 is phosphorylated post DNA damage, and its depletion sensitizes cancer cells to damaging agents that form blocks ahead of the replication forks."
24923443
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"USP20 phosphorylation by ATR does not affect its E3 ligase activity per se , suggesting that USP20 levels, but not catalytic activity, are subjected to ATR regulation."
25355518
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"Currently, we do not know how USP20 phosphorylation affects its binding to HERC2."
25355518
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"One is that USP20 phosphorylation itself affects the binding between USP20 and HERC2."
25355518
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"The other possibility is that USP20 phosphorylation changes USP20 conformation, which in turn prevents HERC2 binding."
25355518
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"Furthermore, USP20 is phosphorylated and therefore inhibited by mTORC1, the master protein kinase that senses nutrient abundance."
34619075
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"Phospho-USP20 was undetectable in β1AR KO mice subjected to TAC, suggesting a role for USP20 phosphorylation in cardiac response to pressure overload."
30538132
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"Under replication stress, ATR-mediated phosphorylation of USP20 results in the disassociation of HERC2 from USP20."
25326330
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"ATM/ATR-mediated phosphorylation of USP20 does not affect its DUB activity; rather, this USP20 phosphorylation enhances the association of USP20 with Rad17 and thereby enhances USP20-mediated deubiquitination of Rad17 ( xref )."
37311534
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"In cancer cells, feeding-induced nutrient stress caused the accumulation of insulin and glucose, which stimulated mTORC1 to phosphorylate USP20."
36755301
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"Phosphorylation of USP20 appears to activate USP20-mediated deubiquitination of HMG-CoA reductase (HMGCR) in the hepatocyte ( xref )."
37311534
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"They found that elevated postprandial blood glucose and insulin levels activate mTORC1 (mechanistic target of rapamycin complex 1), which stabilizes HMGCR (3-hydroxy-methylglutaryl coenzyme A reductase), phosphorylates USP20 (ubiquitin-specific peptidase 20), and upregulates cholesterol biosynthesis."
36382190
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"This occurred in a phosphorylation-dependent manner, because only the non-phosphorylated USP20 was active."
26445063
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"Long-term high-sucrose, high-fat diets induce USP20 phosphorylation, stabilize HMGCR, increases serum cholesterol, and cause metabolic diseases."
36382190
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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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"HMGCR recruited phosphorylated USP20 to form the HMGCR-USP20 complex, which protected HMGCR from proteasome-mediated degradation [ xref ]."
36755301
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"To verify the effect of EA on the downregulation of this signaling pathway, we treated rats with l -leucine by intragastric administration, and observed that the expression of p -mTOR, p -USP20, and HMGCR was increased compared with those in the HFD group (all P < 0.05)."
37916105
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"Considered together, all these data indicate that there was a chronic activity of p -mTOR and higher HMGCR deubiquitination activity by phosphorylating USP20 in hyperlipidemic rats on an HFD diet, increasing cholesterol biosynthesis in the liver, and inducing higher lipid levels in both liver and serum."
37916105
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"It has been demonstrated that feeding induces higher p -mTOR signaling to increase HMGCR deubiquitination via USP20 phosphorylation [ xref ]."
37916105
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"As shown in xref A–E, the relative expression of HMGCR, p -USP20, and p -mTOR during re-feeding in all the groups was significantly increased compared to that measured in the fasted state (all P < 0.01)."
37916105
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"Furthermore, EA markedly decreased the relative expression of HMGCR (P < 0.01), p -USP20 (P < 0.05), and p -mTOR (P < 0.05) in the refed state compared to that in the HFD group."
37916105
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"In the EA + agonist group, the relative expression of HMGCR (P < 0.01), p -USP20 (P < 0.01), and p -mTOR (P < 0.05) was downregulated after re-feeding compared with the agonist group, in which the levels were higher than in the HFD group."
37916105
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"However, the tunica media of atherosclerotic arterial segments demonstrated 1.9 ± 0.2-fold higher levels of phospho-USP20(Ser333) than the nonatherosclerotic arterial segments ( xref )."
37311534
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"Recently, Lu et al. reported that activation of mTORC1 could phosphorylate USP20 to antagonist HMGCR degradation [ xref ]."
37150151
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"Liver and adipose tissues were assessed histologically, and body and liver weight, serum and liver lipid levels, expression of mTOR/ubiquitin-specific peptidase 20 (USP20)/recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and phosphorylation of mTOR and USP20 were measured."
37916105
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"EA at Fenglong point ameliorated hyperlipidemia and hepatocyte steatosis, and decreased p -USP20, p -mTOR and HMGCR expression in the liver by reducing deubiquitination."
37916105
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"Concomitantly, EA prevented the induction of phosphorylated USP20 and mTOR, and HMGCR expression; and reduced the deubiquitination of HMGCR after re-feeding."
37916105
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"As shown in xref E–G, the levels of HMGCR, phosphorylated USP20 ( p -USP20), and p -mTOR were highly elevated in HFD-fed rats compared with those on a normal diet (P < 0.01), and EA treatment markedly alleviated these chronic activities on p -mTOR (P < 0.05) and p -USP20 (P < 0.05) and decreased HMGCR (P < 0.01)."
37916105
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"In contrast, phosphorylation of USP20 at sites distinct from Ser334 does affect USP20 stability."
37311534
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"Together, these data indicated that EA ameliorated the increase in p -mTOR and p -USP20 in the HFD group during re-feeding and counteracted the deubiquitination activity of HMGCR induced by re-feeding ( xref , xref )."
37916105
sparser
"There was much higher p -mTOR signaling and higher HMGCR levels by phosphorylating USP20 in HFHS-fed mice than in chow-fed mice [ xref ]."
37916105
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"However, incubation of this purified USP20 with IRAK1 increased human USP20 Ser333 phosphorylation >2-fold, as detected by our phospho-USP20(Ser333) IgG ( xref , A and B )."
37311534
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"We also focused on the deubiquitination activity of HMGCR and the phosphorylation of mTOR and USP20."
37916105
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"Long-term HFHS-fed mice remained more responsive to the fasting/re-feeding paradigm, displaying much higher levels of mTOR signaling and HMGCR levels by phosphorylating USP20 in the liver."
37916105
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"Phosphorylation of USP20 on Ser334 increased 2.5-fold in response to IL-1β in SMCs transfected with control siRNA ( xref , C and D )."
37311534
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"Furthermore, by silencing IRAK1, we also reduced basal levels of phospho-USP20(Ser334) ( xref , C and D )."
37311534
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"The DNA-damage response induced by prolonged UV exposure or hydroxyurea treatment activates ataxia-telangiectasia mutated (ATM) and ATM and Rad3 related (ATR) kinases, leading to phosphorylation of USP20 at four potential SQ/TQ motifs in hUSP20: T170Q, T232Q, S305Q and S662Q ( xref )."
37311534
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"USP20 phosphorylation confers OXA and ferroptosis resistance of HCC cells."
38124786
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"ATR phosphorylates and stabilizes USP20."
38124786
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"We then wanted to determine the biological function of ATR-mediated phosphorylation of USP20."
25326330
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"We then stably expressed USP20 WT, S132A/368A, and S132D/S368D in HCC primary cell line (from sample T7 with low USP20 expression) to examine the functions of USP20 phosphorylation in HCC cells,."
38124786
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"In our present study, we found that inhibition of ATR significantly reduced the phosphorylation of USP20 and further increased the polyubiquitination of USP20, resulting its destabilization."
38124786
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"Subsequently, the upregulation of postprandial glucose and insulin levels promotes the phosphorylation of USP20 ( xref )."
38322269
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"ATR-mediated phosphorylation of USP20 promotes its dissociation from HERC2."
25326330
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"These results establish the important role of USP20 phosphorylation in ATR-dependent DDR."
25355518
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"Inhibition by phosphorylation of the deubiquitinating enzyme USP20 (Ubiquitin-specific-processing protease 20) favors the activation of the UPS complex by recruiting the E3 ligase NEDD4 and the adapto[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28528970
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"For example, the phosphorylated USP20 binds to ER-localized AMFR/gp78 (autocrine motility factor receptor) and stabilizes HMGCR by cleaving K48- and K63-linked ubiquitin chains, resulting in increased cholesterol biosynthesis within the liver after feeding [ xref ]."
38705724
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"Upon replication stress, ATR-mediated phosphorylation of USP20 promotes dissociation of HERC2 from USP20, stabilizes USP20 and its association with CLASPIN, thus increasing CALSPIN stability and ensuring CHK1 activation."
25326330
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"This study reveals an unexpected regulatory axis from mTORC1 to HMGCR via USP20 phosphorylation and suggests that inhibitors of USP20 could be used to lower cholesterol levels to treat metabolic diseases including hyperlipidaemia, liver steatosis, obesity and diabetes."
33177714
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"Lu et al. demonstrated that mechanistic target of rapamycin complex 1 phosphorylated USP20 at serine 132 and serine 134 and then increased the stability of HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the cholesterol biosynthetic pathway [ xref ]."
35508480
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"USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation."
25355518
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"Using an antibody against consensus ATM/ATR phosphorylation sites (anti-phospho-SQ/TQ), we found that phosphorylation of USP20 at SQ/TQ motifs following HU or UV treatment and USP20 phosphorylation was blocked by caffeine (Figure xref and xref )."
25355518
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"Furthermore, USP20 phosphorylation increased at the early time point in response to UV treatment and decreased when the cells were recovered from DNA damage (Supplementary Figure S4B)."
25355518
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"Since ATR is a major kinase activated by replication stress, we further confirmed the role of ATR in USP20 phosphorylation using cells depleted of ATR by shRNA."
25355518
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"As shown in Figure xref and Supplementary Figure S4C, ATR depletion compromised USP20 phosphorylation at the SQ/TQ motifs and resulted in USP20 downregulation, suggesting that ATR is the major kinase responsible for USP20 phosphorylation and upregulation following replication stress."
25355518
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"There are four potential SQ/TQ motifs in USP20: T170Q, T232Q, S305Q and S662Q. We found that individual mutation at these sites partially affected USP20 phosphorylation, while mutating all four sites (4 mut) abolished USP20 phosphorylation (Figure xref and xref )."
25355518
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"These results suggest that ATR-mediated phosphorylation of USP20 is required for USP20 stabilization through inducing disassociation of HERC2 and USP20."
25355518
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"Moreover, ubiquitin specific peptidase 20 (USP20) improved FTO level through inhibiting FTO degradation while PDIA3 increased FTO level by enhancing USP20 phosphorylation during osteogenic differentiation of MC3T3-E1 cells, suggesting a positive feedback regulatory loop between PDIA3 and FTO."
38321831
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"Besides, ATR phosphorylates and also stabilizes USP20 by unbinding it from HERC2."
31447701
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"It has been reported that mTORC1 promotes cholesterol synthesis by phosphorylating USP20 to protect the HMGCR complex from degradation [ 30 ] and trigger the production of mature SREBP2 [ 33 ] to posi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37150500
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"Mechanistically, HERC2 promotes proteasomal degradation of USP20 (a deubiquitinase that catalyses deubiquitination of K48-linked ubiquitinated substrates) and thereby facilitates proteasomal degradati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34920250
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"Activation of mTORC1 triggers SREBP2 cleavage and translocation (Eid et al, xref ), phosphorylates USP20 and subsequently stabilizes HMGCR at the fasting-feeding transition (Lu et al, xref )."
39824985
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"Subsequently, it was also found that long-term high-sugar and high-fat diet induced increased phosphorylation of USP20, stabilized HMGCR protein and increased cholesterol, which caused metabolic diseases."
35754818