IndraLab
Statements
USP2 affects Delta-actitoxin-Avd1a
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409
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"Consistent with this hypothesis, the structures of USP2, USP8, and OTUB2 with Ub bound in the distal binding site reveal that the relevant serine residues (Ser57 for USP2, XREF_FIG K; Ser20 and 57 for USP8, XREF_FIG J and 6M; and Ser65 for OTUB2, XREF_FIG N) are solvent exposed in the distal binding sites (XREF_FIG H)."
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"The specificity of SJB was confirmed by various experiments : first, we show that SJB potently and selectively block USP1 activity without inhibiting other DUBs (USP2/USP5/USP7/USP14/UCH37); second, SJB inhibited binding of USP1 with HA-Ub-VS probe, but it did not affect labeling of other DUBs with probe; and third, SJB inhibited USP1, but not USP2 or USP7, triggered cleavage of ubiquitin tetramer chains."
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"Consistent with this hypothesis, the structures of USP2, USP8, and OTUB2 with Ub bound in the distal binding site reveal that the relevant serine residues (Ser57 for USP2, XREF_FIG K; Ser20 and 57 for USP8, XREF_FIG J and 6M; and Ser65 for OTUB2, XREF_FIG N) are solvent exposed in the distal binding sites (XREF_FIG H)."
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"In this study, we showed that USP2 is a new bona fide deubiquitylase of SKP2, which is supported by the following lines of evidence: (1) SKP2 binding with USP2 under physiological conditions; (2) the levels of endogenous SKP2 are directly regulated by USP2 manipulation with USP2 knockdown to decrease and USP2 overexpression to increase SKP2; (3) USP2 stabilized SKP2 by cleaving SKP2 polyubiquitylation chains to extend SKP2 half-life; (4) pharmacologic inhibition of USP2 significantly impaired SKP2 stability; and (5) USP2 catalytic-inactive mutant USP2–C276A had no effect on SKP2."
sparser
"In a previously published study of a cohort of 11 pediatric B-ALL patients with the KMT2A-USP2 fusion, three patients presented with central nervous system disease and 8 patients had positive-minimal residual disease at day 33, suggesting a poor prognosis of patients carrying this fusion ( xref )."
sparser
"In other cases, clinical break-apart FISH assays only identified one component of the likely fusion ( NUP98 in sample 0158 and KMT2A in sample 0172), while the partner gene with prognostic significance was only identified after nanopore sequencing, ( NUP98 :: NSD1 and KMT2A::USP2 )."
sparser
"MPAL with KMT2A usually has a B/myeloid immunophenotype (an example case of MPAL with KMT2A::USP2 fusion, B/myeloid (bilineal, pattern 1b, in xref )), although other immunophenotypic variants, including rare cases of AUL and T/myeloid MPAL, have been reported [ xref , xref , xref ]."
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"These data demonstrate that CD8 + T cells, but not CD4 + T cells, are the primary effector cells underlying the combination treatment in these tumor models.Finally, to ascertain whether USP2 inhibition potentiates the efficacy of PD-1/PD-L1 blockade by enhancing p53 function in a tumor cell autonomous manner, we also examined the effects of combination therapy in Balb/c mice bearing p53-null EMT6 tumors."
Gallic acid affects USP2
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Gallic acid binds USP2.
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Gallic acid binds USP2. 10 / 28
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sparser
"Interestingly, preincubation of iodoacetic acid (IAA), a cysteine alkylating agent, with USP2 completely inhibited the binding of biotin-GA to USP2 ( xref ), suggesting that GA may covalently bind to the cysteine(s) of USP2, which is consistent with previous reports that GA can covalently bind to its targets through cysteine residues xref ."
Gallic acid inhibits USP2.
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Gallic acid activates USP2.
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"In this study, we showed that USP2 is a new bona fide deubiquitylase of SKP2, which is supported by the following lines of evidence: (1) SKP2 binding with USP2 under physiological conditions; (2) the levels of endogenous SKP2 are directly regulated by USP2 manipulation with USP2 knockdown to decrease and USP2 overexpression to increase SKP2; (3) USP2 stabilized SKP2 by cleaving SKP2 polyubiquitylation chains to extend SKP2 half-life; (4) pharmacologic inhibition of USP2 significantly impaired SKP2 stability; and (5) USP2 catalytic-inactive mutant USP2–C276A had no effect on SKP2."
USP2 affects gallic acid
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Gallic acid binds USP2. 10 / 28
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sparser
"Interestingly, preincubation of iodoacetic acid (IAA), a cysteine alkylating agent, with USP2 completely inhibited the binding of biotin-GA to USP2 ( xref ), suggesting that GA may covalently bind to the cysteine(s) of USP2, which is consistent with previous reports that GA can covalently bind to its targets through cysteine residues xref ."
USP2 affects cell population proliferation
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USP2 activates cell population proliferation.
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USP2 inhibits cell population proliferation.
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USP2 inhibits cell population proliferation. 10 / 13
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"Taken together, these data suggest that USP2 restricts the proliferation of myeloid cells and thereby inhibits the activation and expansion of IL-22- and IFNγ-producing T cells in the lamina propria during DSS-induced colitis.2.6
USP2 in myeloid cells inhibits immune responses to bacterial infections in the gut."
USP2 affects apoptotic process
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USP2 inhibits apoptotic process.
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USP2 activates apoptotic process.
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USP2 activates apoptotic process. 9 / 12
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"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip (L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."
sparser
"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."
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"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."
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"In light of the shorter half-life of USP2 (compared to that of PER1) (XREF_FIG) and of its rhythmic expression peaking almost simultaneously with that of PER1, the deubiquitination of PER1 by USP2 could be restricted to a specific circadian time and therefore be altering the function and/or localization of PER1 to fine tune the molecular clock in physiological conditions."
"Recently, we showed that the deubiquitinating enzyme ubiquitin-specific peptidase 2 (<span class="match term0">USP2</span>) associates with clock proteins and deubiquitinates PERIOD1 (<span class="match term1">PER1</span>) but does not affect its overall stability."
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"Taken together, these results revealed a previously unrecognized yet critical role of USP2 in the regulation of PPAR-γ signaling and in the pathogenesis of muscle atrophy.Our mechanistic investigations revealed that USP2 prevents muscle atrophy by regulating the stability of PPAR-γ, a key TF implicated in muscle metabolism and insulin sensitivity (31–33)."
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"Using anti-Flag or anti-Myc antibody precipitated protein as input, interactive Myc-USP2 protein (Supplementary Figure 1 B) and interactive Flag-ARID2 (Supplementary Figure 1 C) were, respectively, detected; the above findings provided direct evidence of the interaction of USP2 and ARID2 in cell line models."
sparser
"Using anti-Flag or anti-Myc antibody precipitated protein as input, interactive Myc-USP2 protein (Supplementary Figure xref ) and interactive Flag-ARID2 (Supplementary Figure xref ) were, respectively, detected; the above findings provided direct evidence of the interaction of USP2 and ARID2 in cell line models."
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"Xu et al. found 29 that the expression of the deubiquitinating enzyme USP2 was elevated in angiotensin II-induced cardiac fibroblasts, and that its interaction with β-catenin prevented β-catenin deubiquitination from being degraded, thereby promoting the activation, proliferation, and collagen synthesis of cardiac fibroblasts."
sparser
"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."
reach
"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."
USP2 is modified
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USP2 is phosphorylated.
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rlimsp
"However, USP12 was still able to exert an indirect effect on AR Vs by controlling its phosphorylation through AKT activation (Figure 7F), confirming that AR Vs are still phosphorylated at S213 while this phosphorylation is most likely to be of no consequence for AR V activity as phosphorylation at this site reportedly decreases AR-androgen binding and targets AR for ubiquitination by MDM2 [44], both processes that seem irrelevant to AR V biology."
sparser
"Live-cell imaging of cells expressing EGFP-fused USP2 after laser microirradiation, mapping of domains responsible for recruitment to DSB sites, and analyses of phospho-deficient and phospho-mimetic mutants of USP2 showed that USP2 is recruited to DSB sites in a ATM-dependent manner, and phosphorylation of two critical residues in the N terminus of USP2 is essential for its recruitment to DSBs and interaction with RECQL4."
USP2 is phosphorylated on S57. 2 / 2
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USP2 is phosphorylated. 2 / 2
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USP2 is ubiquitinated.
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ML364 affects USP2
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"Using anti-Flag or anti-Myc antibody precipitated protein as input, interactive Myc-USP2 protein (Supplementary Figure 1 B) and interactive Flag-ARID2 (Supplementary Figure 1 C) were, respectively, detected; the above findings provided direct evidence of the interaction of USP2 and ARID2 in cell line models."
sparser
"Using anti-Flag or anti-Myc antibody precipitated protein as input, interactive Myc-USP2 protein (Supplementary Figure xref ) and interactive Flag-ARID2 (Supplementary Figure xref ) were, respectively, detected; the above findings provided direct evidence of the interaction of USP2 and ARID2 in cell line models."
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USP2 inhibits epithelial to mesenchymal transition.
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USP2 activates epithelial to mesenchymal transition.
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USP2 affects cell cycle
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USP2 activates cell cycle.
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USP2 inhibits cell cycle.
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USP2 affects Neoplasm Invasiveness
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USP2 inhibits Neoplasm Invasiveness.
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USP2 activates Neoplasm Invasiveness.
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USP2 activates Neoplasm Invasiveness. 5 / 5
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"As shown in Figures 4(a) and (b), USP2 shRNA transfection uniformly enhanced H1299 and A549 cell migration and invasion, while USP2 overexpression vector transfection significantly suppressed the migrative and invasive capability of cancer cells.Subsequent wound healing assay suggested that H1299 cells with USP2 shRNAs transfection elevated cancer cell migration and wound healing after 48 h of incubation (Supplementary Figure 2 A-B)."
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"Moreover, although a small-molecule inhibitor of USP2 alone can partially suppress the in vivo growth of p53-wild-type mammary tumor xenografts, more strikingly, USP2 inhibition and PD-1/PD-L1 blockade in combination promote vigorous tumor regression and long-term survival of all tumor-bearing mice."
USP2 affects inflammatory response
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USP2 activates inflammatory response.
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USP2 activates inflammatory response. 5 / 6
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"In addition, results from Masson trichromatic staining showed that collagens (major components of ECM in the gut) (Rieder et al., 2013) accumulated more intensively in the colon tissues from Usp2 mice than Lyz2-Cre;Usp2 mice after colitis induction (Fig. 5D), indicating that knockout of USP2 impairs the ECM remodeling in the colon inflammation."
USP2 inhibits inflammatory response.
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USP2 inhibits inflammatory response. 4 / 4
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"Overexpression of USP2 via tail injection of recombinant adeno-associated virus serotype 9 (AAV9) in TAC-treated male mice has been reported to attenuate pressure-overload-induced ventricular dysfunction, cardiac fibrosis, inflammation, and overall oxidative stress compared with AAV9 control-treated counterparts [31]."
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"These data demonstrate that CD8 + T cells, but not CD4 + T cells, are the primary effector cells underlying the combination treatment in these tumor models.Finally, to ascertain whether USP2 inhibition potentiates the efficacy of PD-1/PD-L1 blockade by enhancing p53 function in a tumor cell autonomous manner, we also examined the effects of combination therapy in Balb/c mice bearing p53-null EMT6 tumors."
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"By its action on the ubiquitination status of PER1, and possibly other clock proteins it interacts with, USP2 appears to exert a broad function, modulating both SCN central clock function (as seen by effects on both period length and response to photic stimuli) as well as peripheral clocks (as exemplified by our observations in embryonic fibroblasts)."
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"Collectively, these data suggest that USP2 negatively regulates TGF-β signaling to suppress myeloid cells proliferation in the lamina propria during DSS-induced colitis, although it promotes TGF-β signaling and exhibits cytostatic effects in multiple non-immune cells.One major function of myeloid cells is to activate T cells during infection and inflammation."
USP2 affects Neoplasm Metastasis
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USP2 activates Neoplasm Metastasis.
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USP2 inhibits Neoplasm Metastasis.
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"Meanwhile, USP2 ablation-induced PD-L1 clearance enhances antitumor immunity in mice via increasing CD8 + T cells infiltration and reducing immunosuppressive infiltration of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), whereas PD-L1 overexpression reverses the tumor growth suppression by USP2 silencing."
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"Moreover, although a small-molecule inhibitor of USP2 alone can partially suppress the in vivo growth of p53-wild-type mammary tumor xenografts, more strikingly, USP2 inhibition and PD-1/PD-L1 blockade in combination promote vigorous tumor regression and long-term survival of all tumor-bearing mice."
"Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1."
"Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1."
"Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1."
"Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1."
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2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP2.
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2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP2.
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Disulfiram affects USP2
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"As SKP2 E3 ligase is responsible for NBS1 ubiquitination during the DSB response, USP2 may also be able to reduce NBS1 ubiquitination through interaction with SKP2, although the importance of this mode of action in stabilizing the MRN complex during the DSB response has not yet been determined.The MRN complex is one of the key factors in the DSB response, and its recruitment to DSB sites and its roles in the DSB response have been well documented in many previous studies."
sparser
"In the present study, we demonstrated that USP2 is a DUB that directly controls KRAS ubiquitination, as supported by the following evidence: 1) overexpression of USP2 stabilizes KRAS; 2) USP2 interacts with KRAS in cells as indicated by the immunoprecipitation and immunofluorescence assays; 3) USP2 directly removes ubiquitin from ubiquitylated KRAS, which leads to KRAS stabilization, whereas USP2 inhibition results in the proteasomal degradation of KRAS."
USP2 affects Interferon
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USP2 activates Interferon.
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USP2 activates Interferon. 1 / 5
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USP2 inhibits Interferon.
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USP2 inhibits Interferon. 2 / 2
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"These data together suggest that inhibition of USP2 promotes the proliferation of macrophages and dendritic cells to activate IL-22- and IFNγ-producing T cells during DSS-induced colitis.We also examined whether targeting USP2 by ML364 inhibited the dysregulation of ECM and promoted tissue repair."
reach
"Taken together, these data suggest that USP2 restricts the proliferation of myeloid cells and thereby inhibits the activation and expansion of IL-22- and IFNγ-producing T cells in the lamina propria during DSS-induced colitis.2.6
USP2 in myeloid cells inhibits immune responses to bacterial infections in the gut."
USP2 affects Carcinoma, Renal Cell
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Particulate Matter affects USP2
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Particulate Matter increases the amount of USP2.
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Particulate Matter decreases the amount of USP2.
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sparser
"In the present study, we demonstrated that USP2 is a DUB that directly controls KRAS ubiquitination, as supported by the following evidence: 1) overexpression of USP2 stabilizes KRAS; 2) USP2 interacts with KRAS in cells as indicated by the immunoprecipitation and immunofluorescence assays; 3) USP2 directly removes ubiquitin from ubiquitylated KRAS, which leads to KRAS stabilization, whereas USP2 inhibition results in the proteasomal degradation of KRAS."
Air Pollutants affects USP2
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Air Pollutants increases the amount of USP2.
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Air Pollutants decreases the amount of USP2.
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Catenin affects USP2
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sparser
"However, inhibiting the Wnt /β‐catenin canonical pathway and down‐regulating β‐catenin can achieve the aim of improving the ventricular remodelling. xref Actually, one of the major mechanisms of β‐catenin regulation is ubiquitination, beside which DUBs, such as USP47, USP20, and USP2, have also been shown to deubiquitinate and stabilize β‐catenin directly. xref , xref , xref In this study, β‐catenin was down‐regulated by USP2 inhibition, which prompted us to assess the interaction between USP2 and β‐catenin."
Bisphenol A affects USP2
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Bisphenol A decreases the amount of USP2.
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Bisphenol A increases the amount of USP2.
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Benzo[a]pyrene affects USP2
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Benzo[a]pyrene increases the amount of USP2. 6 / 6
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USP2 affects ferroptosis
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USP2 activates ferroptosis.
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USP2 inhibits ferroptosis.
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USP2 affects catenin
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sparser
"However, inhibiting the Wnt /β‐catenin canonical pathway and down‐regulating β‐catenin can achieve the aim of improving the ventricular remodelling. xref Actually, one of the major mechanisms of β‐catenin regulation is ubiquitination, beside which DUBs, such as USP47, USP20, and USP2, have also been shown to deubiquitinate and stabilize β‐catenin directly. xref , xref , xref In this study, β‐catenin was down‐regulated by USP2 inhibition, which prompted us to assess the interaction between USP2 and β‐catenin."
USP2 affects Reactive Oxygen Species
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USP2 inhibits Reactive Oxygen Species.
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USP2 activates Reactive Oxygen Species.
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"Silencing of USP2 expression decreased migration and invasion in LM2-4175 and SCP46 cells in association with the downregulation of matrix metalloproteinase-2 (MMP2) expression, whereas overexpression of USP2 in MDA-MB-468 and MDA-MB-231 cells enhanced migration and invasion and upregulated the expression of MMP2."
sparser
"Though the reason for this peculiarity is presently unknown, it may lie in the fact that the USP2-45 binding to Ca V α 2 δ-1 might disrupt the chaperone role of the auxiliary subunit, leading to a reduction of the Ca V 1.2α 1 pore-forming subunit trafficked to the plasma membrane [ xref ]."
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"Importantly, by deubiquitinating CCAAT/enhancer binding protein alpha (C/EBPα), USP2 also regulates 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby playing a vital role in the homeostasis of glucocorticoids within liver cells16.In this study, we found that high dietary fructose consumption promotes MASLD development and progression in C57BL/6J mice, identified Usp2 as a specific fructose-responsive gene, and revealed that the USP2-mediated C/EBPα/11β-HSD1 signaling is involved in disrupting cortisol homeostasis."
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"Importantly, by deubiquitinating CCAAT/enhancer binding protein alpha (C/EBPα), USP2 also regulates 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby playing a vital role in the homeostasis of glucocorticoids within liver cells16.In this study, we found that high dietary fructose consumption promotes MASLD development and progression in C57BL/6J mice, identified Usp2 as a specific fructose-responsive gene, and revealed that the USP2-mediated C/EBPα/11β-HSD1 signaling is involved in disrupting cortisol homeostasis."
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"Our research indicates that fructose exposure leads to the upregulation of C/EBPα and 11β-HSD1, unveiling a mechanism by which USP2-mediated activation of C/EBPα and 11β-HSD1 is implicated in the onset and progression of MASLD.The liver is the central viscus for converting inactive cortisone into active cortisol via 11β-HSD132-34."
sparser
"Though the reason for this peculiarity is presently unknown, it may lie in the fact that the USP2-45 binding to Ca V α 2 δ-1 might disrupt the chaperone role of the auxiliary subunit, leading to a reduction of the Ca V 1.2α 1 pore-forming subunit trafficked to the plasma membrane [ xref ]."
Sodium arsenite affects USP2
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Sodium arsenite increases the amount of USP2.
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Sodium arsenite decreases the amount of USP2.
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Monoubiquitin affects USP2
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USP2-AS1 affects USP2
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USP2 affects proteolysis
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USP2 inhibits proteolysis.
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USP2 activates proteolysis.
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USP2 affects monoubiquitin
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"Based on this idea, a putative protein digestion mechanism might reduce the excessive accumulation of UCP2 in C2C12 cells.As found in the current study, the inhibition of USP2 interrupts mitochondrial ATP synthesis in myoblasts, leading to defects in proliferation and differentiation [33,42]."
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"Considering that the tissue distribution of USP2 is also relatively ubiquitous [50], USP2 might prevent oxidative stress in various tissues through the preservation of UCP2.The lack of USP2 dramatically repressed UCP2 at the mRNA level, implying that USP2 stimulates the transcription of the Ucp2 gene."
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"Ubiquitin specific peptidase 2 (USP2) expression is decreased in patients with type 2 diabetes and mouse models of diabetes-induced muscle atrophy.USP2 can enhance insulin sensitivity and improve muscle mass and function in diabetic mice.USP2 stabilizes PPAR-gamma via deubiquitination to regulate muscle atrophy, uncovering a key mechanism in this process.The findings indicate the USP2-PPAR-gamma axis has potential as a therapeutic target for metabolic disorders and sarcopenia."
USP2 affects Hypertrophy
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USP2 activates Hypertrophy.
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USP2 inhibits Hypertrophy.
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USP2 inhibits Hypertrophy. 2 / 2
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"In addition, by comparing the GEO dataset and the mRNA level of USP2 in hypertrophic heart induced by trans-arterial coarctation (TAC), it was determined that the expression of USP2 was downregulated in hypertrophic heart, and the overexpression of USP2 could relieve the cardiac hypertrophy induced by TAC."
USP2 affects Cell Survival
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USP2 activates Cell Survival.
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USP2 inhibits Cell Survival.
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sparser
"Using anti-Flag or anti-Myc antibody precipitated protein as input, interactive Myc-USP2 protein (Supplementary Figure xref ) and interactive Flag-ARID2 (Supplementary Figure xref ) were, respectively, detected; the above findings provided direct evidence of the interaction of USP2 and ARID2 in cell line models."
Valproic acid affects USP2
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Valproic acid increases the amount of USP2.
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Valproic acid decreases the amount of USP2.
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USP2 affects signal transduction
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USP2 inhibits signal transduction.
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USP2 inhibits signal transduction. 2 / 2
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"Consistently, we found that PPAR-γ knockdown increased and Usp2 overexpression decreased the expression of FoxO signaling pathway-related genes, including cyclin G2 (Ccng2), cyclin-dependent kinase inhibitor 1B (Cdkn1b), retinoblastoma-like protein 2 (Rbl2), and Bcl-2 interacting protein 3 (Bnip3) (Fig. 6B)."
USP2 activates signal transduction.
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USP2 affects regulation of cell cycle
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USP2 inhibits regulation of cell cycle.
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USP2 activates regulation of cell cycle.
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USP2 activates regulation of cell cycle. 1 / 1
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USP2 affects muscle atrophy
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USP2 inhibits muscle atrophy.
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USP2 inhibits muscle atrophy. 2 / 2
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"Taken together, these results revealed a previously unrecognized yet critical role of USP2 in the regulation of PPAR-γ signaling and in the pathogenesis of muscle atrophy.Our mechanistic investigations revealed that USP2 prevents muscle atrophy by regulating the stability of PPAR-γ, a key TF implicated in muscle metabolism and insulin sensitivity (31–33)."
USP2 activates muscle atrophy.
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USP2 activates muscle atrophy. 2 / 2
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"We investigated the changes in endogenous USP2 expression in diabetes-induced muscle atrophy mouse models and found that the Gas and TA muscles of diabetic mice (STZ + HFD; spontaneous diabetes mouse model) had lower USP2 levels than their respective Ctrl groups (Supplementary Fig. 1B and C)."
USP2 affects gluconeogenesis
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USP2 affects extracellular matrix
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USP2 activates extracellular matrix. 4 / 4
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"Taken together, these data suggest that pharmacological inhibition of USP2 prevents dysregulation of ECM and promotes the integrity of the epithelial barrier in the gut during inflammation, and that targeting USP2 might provide a potential strategy for therapeutic intervention of inflammatory diseases in the gut.3
Discussion."
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"In addition, results from Masson trichromatic staining showed that collagens (major components of ECM in the gut) (Rieder et al., 2013) accumulated more intensively in the colon tissues from Usp2 mice than Lyz2-Cre;Usp2 mice after colitis induction (Fig. 5D), indicating that knockout of USP2 impairs the ECM remodeling in the colon inflammation."
reach
"These data together suggest that knockout of USP2 in myeloid cells inhibits dysregulation of ECM in the colon after DSS treatment.To further confirm that the myeloid cells trained the epithelium to induce dysregulation of ECM, we isolated RFP cells from the LPMCs of Lyz2-Cre;Usp2 Ai14 mice Lyz2-Cre;Ai14 mice that were treated with DSS and cultured these cells for 18 h."
USP2 affects cell growth
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USP2 activates cell growth.
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USP2 inhibits cell growth.
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USP2 inhibits cell growth. 1 / 1
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USP2 affects Proteasome
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USP2 binds Proteasome.
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USP2 activates Proteasome.
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"Given that the protein levels of USP2 or C276A were comparable in USP2- and C276A-transfected cells, USP2 modulates PGC1α levels via ubiquitin isopeptidase activity.Finally, we examined whether USP2 directly digested the lysine48 (K48)-linked polyubiquitin chains on PGC1α, since K48-linked polyubiquitin chanins represent a canonical signal for proteasome degradation [41]."
sparser
"Using anti-Flag or anti-Myc antibody precipitated protein as input, interactive Myc-USP2 protein (Supplementary Figure xref ) and interactive Flag-ARID2 (Supplementary Figure xref ) were, respectively, detected; the above findings provided direct evidence of the interaction of USP2 and ARID2 in cell line models."
PUVA affects USP2
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Tetrachloromethane affects USP2
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Epithelial sodium channel affects USP2
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UbV.2.6 affects USP2
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Ub-AMC affects USP2
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USP2 affects epithelial sodium channel
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USP2 affects cytokine production
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USP2 affects cell migration
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USP2 activates cell migration. 3 / 3
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"As shown in Figures 4(a) and (b), USP2 shRNA transfection uniformly enhanced H1299 and A549 cell migration and invasion, while USP2 overexpression vector transfection significantly suppressed the migrative and invasive capability of cancer cells.Subsequent wound healing assay suggested that H1299 cells with USP2 shRNAs transfection elevated cancer cell migration and wound healing after 48 h of incubation (Supplementary Figure 2 A-B)."
USP2 affects cell differentiation
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USP2 affects cell death
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USP2 affects calcium(2+)
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USP2 affects Ub-AMC
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"These data together suggest that inhibition of USP2 promotes the proliferation of macrophages and dendritic cells to activate IL-22- and IFNγ-producing T cells during DSS-induced colitis.We also examined whether targeting USP2 by ML364 inhibited the dysregulation of ECM and promoted tissue repair."
reach
"Taken together, these data suggest that USP2 restricts the proliferation of myeloid cells and thereby inhibits the activation and expansion of IL-22- and IFNγ-producing T cells in the lamina propria during DSS-induced colitis.2.6
USP2 in myeloid cells inhibits immune responses to bacterial infections in the gut."
sparser
"Additionally, in the subsequent co-immunoprecipitation analysis to examine the association of USP2 with ErbB2, USP2 was readily pulled down by immunoprecipitated ErbB2 especially in cells treated with 17-AAG, suggesting stronger association between USP2 and ubiquitylated ErbB2 (Fig. xref )."
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"These data together suggest that knockout of USP2 increases myeloid cells in the lamina propria of mice after DSS treatment.We next sorted the RFP cells from the CD45 LPMCs of Lyz2-Cre;Ai14 and Lyz2-Cre;Usp2 Ai14 mice that were induced colitis and performed transcriptome sequencing assays (Fig. 2A)."
RA-9 affects USP2
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3
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"Additionally, in the subsequent co-immunoprecipitation analysis to examine the association of USP2 with ErbB2, USP2 was readily pulled down by immunoprecipitated ErbB2 especially in cells treated with 17-AAG, suggesting stronger association between USP2 and ubiquitylated ErbB2 (Fig. xref )."
Dietary Fats affects USP2
3
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"However, the free running period (tau), a key intrinsic characteristic of the central circadian clock, was significantly increased in Usp2 KO mice (XREF_FIG; XREF_TABLE) (also reproduced in an additional group of mice, data not shown), suggesting the involvement of USP2 in the molecular clockwork."
Tioguanine affects USP2
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1
1
Tetraphene affects USP2
2
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Pirinixic acid affects USP2
2
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Phenylmercury acetate affects USP2
2
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Phenobarbital affects USP2
2
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Magnetite nanoparticle affects USP2
2
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HPTH 1-38 affects USP2
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2
GAcrp affects USP2
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2
Folic acid affects USP2
2
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Cannabidiol affects USP2
2
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Benzo[b]fluoranthene affects USP2
2
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USP2 affects gene expression
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2
USP2 affects doxorubicin
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2
USP2 affects Wnt/β-catenin
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2
USP2 affects ML364
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2
USP2 affects LDL
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2
USP2 affects Insulin Resistance
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2
USP2 affects Infections
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2
USP2 affects Hyperglycemia
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2
USP2 activates Hyperglycemia. 2 / 2
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2
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"USP22 in pancreatic beta-cells, USP2 in adipose tissue macrophages, USP9X, 20, and 33 in myocytes, USP4, 7, 10, and 18 in hepatocytes, and USP2 in hypothalamus improve hyperglycemia, whereas USP19 in adipocytes, USP21 in myocytes, and USP2, 14, and 20 in hepatocytes promote hyperglycemia."
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"Given that HSD1 converts circulating inactive cortisone to active cortisol [107], hepatic USP2 causes hyperglycemia by activating glucocorticoid signaling.Sustained low-grade endoplasmic reticulum (ER) stress induced by low doses of tunicamycin (200 μg/kg) treatment for two weeks increased hepatic gluconeogenesis and resulted in hyperglycemia [103]."
USP2 affects Glucose Intolerance
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1
1
USP2 affects Glioblastoma
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2
USP2 affects DNA-templated transcription
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1
1
USP2 affects DNA Breaks, Double-Stranded
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2
USP2 affects D1
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2
USP2 affects Bacterial Infections
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1
SJB3-019A affects USP2
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1
Reactive Oxygen Species affects USP2
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1
Proteasome affects USP2
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2
Nanotubes, Carbon affects USP2
2
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D1 affects USP2
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2
reach
"Among these proteins, EBF2 has been demonstrated as the pivotal regulatory role in the development of brown adipose and adaptive thermogenesis [32], which piqued our interest.Indeed, RT-qPCR and western blot analysis of EBF2 showed that the protein levels of EBF2 were significantly decreased in the Usp2 knockdown BAT compared to controls, with comparable mRNA levels of Ebf2 (Figure 6E,F)."
AM146 affects USP2
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2
17beta-estradiol affects USP2
2
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1,2-dichloroethane affects USP2
2
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2
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Trovafloxacin affects USP2
1
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Streptozocin affects USP2
1
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SandostatinLAR affects USP2
1
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Resveratrol affects USP2
1
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Perfluorooctanoic acid affects USP2
1
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Perfluorooctane-1-sulfonic acid affects USP2
1
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Nickel sulfate affects USP2
1
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1
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Lipopolysaccharide affects USP2
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Lipopolysaccharide inhibits USP2. 1 / 1
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1
Isoprenaline affects USP2
1
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Iodoacetic acid affects USP2
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1
Iodoacetic acid inhibits USP2. 1 / 1
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1
reach
"Interestingly, preincubation of iodoacetic acid (IAA), a cysteine alkylating agent, with USP2 completely inhibited the binding of biotin-GA to USP2 (Supporting Information Fig. S8), suggesting that GA may covalently bind to the cysteine(s) of USP2, which is consistent with previous reports that GA can covalently bind to its targets through cysteine residues56."
Hsa-miR-493-5p affects USP2
1
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Hsa-miR-4667-5p affects USP2
1
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Graphene oxide affects USP2
1
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Doxorubicin affects USP2
1
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Dicrotophos affects USP2
1
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Decabromodiphenyl ether affects USP2
1
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Azoxystrobin affects USP2
1
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Antithrombin affects USP2
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1
Amiodarone affects USP2
1
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All-trans-retinoic acid affects USP2
1
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USP2 affects pro-degradation HSP90 ErbB2 respective therapeutic windows
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1
eidos
"Through promoting ErbB2 ubiquitylation , USP2 inhibitor is expected to augment the pro-degradation effects of HSP90 inhibitors toward ErbB2 within their respective therapeutic windows , thus eliciting potent anti-tumor effects with tolerable adverse side effects , which warrants further investigations and clinical evaluations ."
USP2 affects polyubiquitin chain
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USP2 affects lipopolysaccharide
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USP2 leads to the deubiquitination of lipopolysaccharide. 1 / 1
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1
USP2 affects keratinocyte differentiation
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USP2 inhibits keratinocyte differentiation. 1 / 1
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1
USP2 affects collagen biosynthetic process
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USP2 activates collagen biosynthetic process. 1 / 1
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1
USP2 affects cellular metabolic process
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1
USP2 activates cellular metabolic process. 1 / 1
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1
USP2 affects alpha-induced apoptosis
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1
USP2 affects acute respiratory syndrome coronavirus papain-like protease
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1
eidos
"Meanwhile , drug specificity should be taken into consideration , because many chemical inhibitors have unexpected molecular targets [ 159 ] ; for example , a recent paper reported that a USP2 blocker also inhibits severe acute respiratory syndrome coronavirus 2 papain-like protease [ 160 ] ."
USP2 affects abundance Na H exchange regulatory cofactor
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1
USP2 affects Ub chain
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1
USP2 affects USP2 activation
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1
USP2 affects TNF receptor
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1
USP2 affects SCN.3 Results
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1
USP2 affects RUXN2
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1
USP2 affects Polyubiquitin
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USP2 inhibits Polyubiquitin. 1 / 1
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1
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"These data demonstrate that CD8 + T cells, but not CD4 + T cells, are the primary effector cells underlying the combination treatment in these tumor models.Finally, to ascertain whether USP2 inhibition potentiates the efficacy of PD-1/PD-L1 blockade by enhancing p53 function in a tumor cell autonomous manner, we also examined the effects of combination therapy in Balb/c mice bearing p53-null EMT6 tumors."
USP2 affects Neoplastic Stem Cells
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1
USP2 activates Neoplastic Stem Cells. 1 / 1
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1
USP2 affects NF-kappaB basal
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1
USP2 affects K63-linked polyubiquitination TRAF2
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1
USP2 affects INSRbeta-GFP
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1
USP2 affects Hydrogen-Ion Concentration
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1
USP2 activates Hydrogen-Ion Concentration. 1 / 1
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USP2 affects HW/BW
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USP2 affects HSD1 mRNA
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USP2 affects EcR-A
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USP2 affects E3_Ub_ligase
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1
USP2 deubiquitinates E3_Ub_ligase. 1 / 1
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1
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"These data together suggest that knockout of USP2 in myeloid cells inhibits the NF-κB signaling pathway and the expression of pro-inflammatory cytokines and chemokines and promotes the expression of cell cycle-related genes in the myeloid cells of lamina propria from mice treated with DSS.2.4
USP2 inhibits the proliferation of macrophages and dendritic cells in the lamina propria during DSS-induced colitis."
USP2 affects BCL2L2-PABPN1
1
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USP2 affects Aurora-A
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1
USP2 affects Ang II-induced
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Sleep Deprivation affects USP2
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1
Sleep Deprivation decreases the amount of USP2. 1 / 1
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1
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"SD also significantly decreased expression levels of Rbm3 and Hnrpdl (mRNA metabolism and trafficking (Kawamura et al. 2002; Smart et al. 2007)) and Usp2 (deubiquitination and control of circadian rhythms (Metzig et al. 2011; Scoma et al. 2011; Yang et al. 2012)) (Fig. 3B; two-way ANOVA for each, P < 0.05)."
S-nitrosoglutathione affects USP2
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N-nitrosodiethylamine affects USP2
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1
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"Indeed, in multiple lung cancer cell lines, ML364 reduced the levels of SKP2, as well as MDM2 and Aurora-A, two known substrates of USP2 (23, 31), serving as the positive controls, in a dose- (Fig. 3A) and time-dependent manner (Fig. 3B), which can be completely rescued by MG132 (Fig. 3C)."
Lipopolysaccharides affects USP2
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L-methionine affects USP2
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EcR-A affects USP2
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1
Beta-elicitin cryptogein affects USP2
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1
Beta-elicitin cryptogein ubiquitinates USP2. 1 / 1
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1
Benzo[k]fluoranthene affects USP2
1
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"These data indicate that MXD3 direct transcriptional regulation could account for both phenotypes described in this paper, namely proliferation (upregulation of putative direct targets IRF4, FBL, HTR1B) and growth arrest and apoptosis (upregulation of RUNX1T1 and BMP3; downregulation of USP2 and MYCL1) as shown in XREF_TABLE."
BCL2L2-PABPN1 affects USP2
1
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Aurora-A affects USP2
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1
1
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1H-pyrazole affects USP2
1
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1,2-dimethylhydrazine affects USP2
1
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