IndraLab
Statements
USP25 is modified
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90
USP25 is phosphorylated.
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53
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"Our data indicate that phosphorylation of USP21 differently affects DNA and RNA virus signaling."
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sparser
"These data collectively suggest that p38-mediated USP21 phosphorylation may play different roles in host defense against DNA and RNA virus infection."
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sparser
"Interestingly, we also noticed that the phosphorylated USP21 was mostly localized at the perinuclear microsome ( xref ), which is similar to the subcellular localization of STING."
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sparser
"Moreover, differentiation cues promote ERK-mediated phosphorylation and dissociation of USP21 from Nanog, thus leading to Nanog degradation."
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sparser
"Recently, the tyrosine kinase SYK has been found to phosphorylate USP25, predictably on the Tyr 740 residue."
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sparser
"We therefore examined whether the phosphorylation of USP21 at these sites are involved in its interaction with STING."
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sparser
"Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses."
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sparser
"Physiologically, our data from FACS showed that intravenous injection of HSV-1 into mice significantly induced the phosphorylation of USP21 in blood cells, which was correlated with the phosphorylated p38 levels ( xref )."
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sparser
"We next aimed to identify the protein kinase that regulates USP21 phosphorylation under HSV-1 infection by screening a library of kinase inhibitors."
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sparser
"We analysed USP21 phosphorylation by using a phospho-Tag gel and found that both endogenous and exogenous USP21 were significantly phosphorylated upon the activation of ERK ( xref ; xref )."
USP25 is sumoylated.
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32
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sparser
"To measure activity, we compared sumoylated USP25 with USP25 that was released from USP25SUMO3 by isopeptidase treatment (GST-SENP1)."
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sparser
"Here we describe a mechanism that contributes to paralog-specific sumoylation of USP25 both in vitro and in vivo: a noncovalent SUMO interaction motif (SIM) in USP25 recruits SUMO2/3 more efficiently,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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sparser
"Given that only 50% of USP25 was sumoylated (based on densitometry), this suggests a residual activity of sumoylated USP25 of 34%."
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sparser
"Our finding that USP25 sumoylation within or close to the UIM domains inactivates USP25 adds another mechanism to a surprisingly short list of regulatory events known for deubiquitinating enzymes ()."
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sparser
"Since it interacts more efficiently with SUMO2/3 compared to SUMO1 in binding assays, we wondered whether sumoylation of USP25 would also be more efficient with SUMO2/3."
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sparser
"As shown in D, sumoylated USP25 is less efficient in ubiquitin chain hydrolysis than deconjugated USP25 (compare decrease in tetra-ubiquitin chains)."
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sparser
"USP25 sumoylation indeed inhibits the catalytic activity of USP25 imposed by its reduced binding to polyubiquitin chains [ xref ]."
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sparser
"Other reported examples include SUMOylation of the deubiquitinating enzyme USP25 which impairs binding to and hydrolysis of ubiquitin chains ( xref ), the E2 ubiquitin conjugation enzyme E2-25K, which prevents its interaction with the ubiquitin E1 enzyme ( xref ), and the E3 ubiquitin ligase RNF4 that target its substrates via SUMO/SIM interaction ( xref ; xref )."
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sparser
"This lysine is located at the beginning of UIM1 and most interestingly, had been previously reported to be the main acceptor for USP25 sumoylation, suggesting a dual regulatory role for this residue."
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sparser
"Noticeably, the non-covalent binding of SUMO is a prerequisite for efficient sumoylation of Usp25 ( 15,16 )."
USP25 is ubiquitinated.
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5
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sparser
"Cigarette smoke promoted USP25 ubiquitination and proteasomal degradation, enhancing the degradation of HDAC11."
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sparser
"Given that deletion of UIMs, although clearly diminishing USP25 ubiquitination, did not completely preclude it, other less preferential sites might become alternative acceptor sites for ubiquitination."
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sparser
"Phosphorylation of USP25 can decrease its protein level in a proteasomal degradation-independent manner by inhibiting the ubiquitination of USP25."
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sparser
"Concomitantly, CSE treatment accelerates a ubiquitin specific protease USP25 ubiquitination and degradation."
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"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I and TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
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"Previous study indicated that USP21 can also bind RIG-I to regulate SeV infection."
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"Our data showed that USP21 bound to RIG-I via multiple regions, which were different from the binding regions to STING (XREF_FIG)."
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sparser
"Usp21 knockout mice showed enhanced antiviral responses to SeV and VSV, but unlike USP3, viral infection was not necessary to facilitate the interaction between RIG-I and USP21."
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sparser
"In antiviral responses, USP21 binds to and deubiquitinates RIG-I in the cytoplasm to exert an immunomodulatory effect; USP21 can also hydrolyzes the K27/63-linked polyubiquitin chain on STING to negatively regulate DNA virus-induced type I interferon production [ xref ]."
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"Usp21 knockout mice showed enhanced antiviral responses to SeV and VSV, but unlike USP3, viral infection was not necessary to facilitate the interaction between RIG-I and USP21."
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"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25.In recent years, USP25 has been extensively studied and some novel functions have been revealed."
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sparser
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
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sparser
"USP25 interacts with RIG-I and TRAF6. (A, B) HEK-293T cells grown in 100-mm dishes were co-transfected with the indicated plasmids encoding the RIG-I (A) or TRAF6 (B) expression vector (4 μg) and HA-USP25WT/ HA-USP25C178A/ HA-USP25H607A (4 μg) using Lipofectamine 2000."
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sparser
"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see Figure S1 )."
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sparser
"Previous study indicated that USP21 can also bind RIG-I to regulate SeV infection ( xref )."
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"Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling."
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"USP17 and USP25 also deubiquitinate RIG-I in a different manner; that is, USP17 stabilizes RIG-I by K48-deubiquitination, while USP25 inhibits RIG-I degradation by K63-deubiquitination [37, 38] ."
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"Therefore, it is highly likely that USP21 acts as a RIG-I polyubiquitination guard to prevent extensive RIG-I polyubiquitination."
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"In antiviral responses, USP21 binds to and deubiquitinates RIG-I in the cytoplasm to exert an immunomodulatory effect; USP21 can also hydrolyzes the K27/63 linked polyubiquitin chain on STING to negatively regulate DNA virus induced type I interferon production [XREF_BIBR]."
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"We reasoned that USP21 might deubiquitinate RIG-I to inhibit virus induced IRF3 activation."
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"USP21 was also reported to antagonize the ubiquitination of anti-viral sensor RIG-I, implicating USP21 as a negative regulator of type-I interferon production and anti-viral immunity (Fan et al., 2014[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In addition, wild-type USP25 significantly inhibits ubiquitination of RIG-I, TRAF2, and TRAF6, which is essential for activation of type I IFN signaling."
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"We observed that overexpression of USP25 significantly inhibited ubiquitination of RIG-I (XREF_FIG), TRAF2 (XREF_FIG), and TRAF6 (XREF_FIG)."
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"We observed that overexpression of USP25 significantly inhibited ubiquitination of RIG-I (Figure 7B), TRAF2 (Figure 7D), and TRAF6 (Figure 7E)."
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"Overexpression of USP21 inhibited RNA virus induced RIG-I polyubiquitination and RIG-I-mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-alpha and beta production, and antiviral responses in MEFs in response to RNA virus infection."
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"We observed that overexpression of USP25 significantly inhibited ubiquitination of RIG-I (Figure Figure 7E )."
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"We further examined the role of USP21 in the inhibition of SeV induced RIG-I polyubiquitination and found that overexpression of USP21 WT but not C221A mutant inhibited SeV induced polyubiquitination of both FLAG tagged and endogenous RIG-I (XREF_FIG)."
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"In particular, USP3, USP21, USP25 and USP15 have all been shown to directly inhibit RIG-I."
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"The deubiquitinases USP3 and USP21 inhibit RIG-I activity by removing K63-linked ubiquitin chains."
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"USP21 and USP15 remove K63-linked polyubiquitin chains from RIG-I and block the ability of RIG-I to induce IFN-β 24,25 ."
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"Interestingly, USP21 inhibits both TRIM25- and RNF135 mediated antiviral response and RIG-I activation (XREF_FIG and not depicted)."
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"Collectively, these findings suggest that USP25 inhibits RIG-I and MDA5-dependent type I IFN signaling."
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"Conversely, the removal of Lys63-linked ubiquitylation by the cellular deubiquitylating enzymes (DUBs) ubiquitin C-terminal hydrolase 3 (USP3), USP21 and CYLD, represses RIG-I signalling (reviewed in Ref."
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"Similarly, USP21 has been reported to negatively regulate RIG-I by removing K63 linked ubiquitination [XREF_BIBR]."
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"In the immune system, USP21 negatively regulates antiviral response by deubiquitinating RIG-1 14."
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"To the best of our knowledge, at least nine DUBs, A20, CYLD, USP3, USP5, USP14, USP15, USP21, USP25, and USP27X, have been proposed to counteract the K63linked ubiquitination of RIG-I and, thereby attenuate downstream signaling and IFN-b production ( Table 1 and Figure 3 ) (58, 76, 93) ."
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"Consistently, endogenous USP21 and RIG-I coimmunoprecipitated in MEFs (XREF_FIG) and SeV induced a stronger RIG-I polyubiquitination in USP21 -/- MEFs compared with that in WT MEFs (XREF_FIG)."
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"Moreover, USP21 deubiquitinated RNF135 mediated RIG-I polyubiquitination both in vivo and in vitro (XREF_FIG)."
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"We further examined the role of USP21 in the inhibition of SeV induced RIG-I polyubiquitination and found that overexpression of USP21 WT but not C221A mutant inhibited SeV induced polyubiquitination of both FLAG tagged and endogenous RIG-I (XREF_FIG)."
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"The deubiquitinase USP21 targets RIG-I for deubiquitination, thus dampening interferon production and activation of IFN responsive genes in response to RNA viruses."
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"Ubiquitylation events are reversible processes, and, accordingly, several deubiquitylating enzymes, in particular ubiquitin specific peptidase 3 (USP3), USP21 and CYLD lysine 63 deubiquitinase (CYLD), modulate RIG-I signalling by removing K63-polyubiquitin chains, although with unique kinetics."
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"However, our studies explain that USP25 negatively modulates RIG-I/MDA5-dependent type I IFN signaling."
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"USP17 and USP25 also deubiquitinate RIG-I in a different manner; that is, USP17 stabilizes RIG-I by K48-deubiquitination, while USP25 inhibits RIG-I degradation by K63-deubiquitination [37, 38] ."
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"However, our studies explain that USP25 negatively modulates RIG-I and MDA5-dependent type I IFN signaling."
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"To investigate whether USP21 interacts with Nanog, co-immunoprecipitation assays were performed."
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"Here we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs)."
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"Taken together, the results indicate that USP21 can interact with Nanog both in vivo and in vitro."
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"The K to R mutations did not affect the interaction between USP21 and Nanog (XREF_SUPPLEMENTARY), suggesting that binding of USP21 was independent of Nanog ubiquitination."
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sparser
"This phosphorylation reduced the binding of USP21 to Nanog and led to Nanog degradation."
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sparser
"Moreover, activation of ERK1 by co-expression of a constitutively active MEK1 (MEK1 CA ) in HEK293T cells significantly impaired the interaction between USP21 and Nanog ( xref )."
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sparser
"In this study, we have identified a novel deubiquitinating enzyme USP21 which interacts with NANOG by both yeast two hybrid screening for DUBs and immunoprecipitation analyses."
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sparser
"This phosphorylation reduced the binding of USP21 to Nanog and led to Nanog degradation."
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"USP21 directly interacts with NANOG through its ubiquitin carboxyl-terminal hydrolase domain (UCH), and the phosphorylation of USP21 by ERK1 prevents this binding, leaving this site exposed for ubiquitination, ultimately leading to NANOG degradation by the UPS ( xref )."
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"Furthermore, treatment of mESCs with FGF4 reduced the interaction between Nanog and USP21 in mESCs in a manner that could be reversed by the MEK inhibitor PD0325901 (XREF_FIG)."
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"Since USP21 is a DUB, we examined whether USP21 could directly interact with and deubiquitinate Nanog."
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"USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency."
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"USP21 deubiquitylates the K48-type linkage of the ubiquitin chain of Nanog, stabilizing Nanog."
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"For example, Oct4 and Sox2 protein levels are regulated by the E3 ligase WWP2, and ubiquitin-specific-processing protease 21 (Usp21) deubiquitinates and stabilizes Nanog, which maintains pluripotency, while FBXW8, an E3 ligase, ubiquitinates and destabilizes Nanog, thereby promoting ESC differentiation."
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"Considering that USP21 deubiquitylates Nanog, we sought to examine the functional roles of USP21 in mESCs."
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"Collectively, these data suggest that USP21 can deubiquitylate and stabilize Nanog."
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"Recently, three groups independently identified ubiquitin specific peptidase 21 (USP21) as an efficient deubiquitylase that reverses Nanog polyubiquitylation and stabilizes Nanog protein."
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"Co-expression of either USP21 isoform significantly prolonged the half-life of Nanog (XREF_FIG)."
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"Overexpression of USP21 prolonged the protein half-life of Nanog to ~ 2h, whereas the catalytically inactive mutant USP21 C221A had no such effects (XREF_FIG)."
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"They further demonstrated that USP21 prevents the degradation of Nanog through deubiquitylation and thus promote maintenance of embryonic stem cells (ESCs)."
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"USP21 mediated Nanog stabilization is enhanced in mouse ESCs and this stabilization is required to maintain the pluripotential state of the ESCs."
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"USP21 could significantly enhance the stability of Nanog and then maintain the self-renewal of stem cells."
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"Overexpression of USP21, but not the catalytically inactive mutant C221A, led to increased Nanog levels in a dose dependent way (XREF_FIG), suggesting that USP21 upregulation of Nanog expression is dependent on DUB enzyme activity."
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"Through the screen, we found that USP21 significantly upregulated Nanog levels, whereas other DUBs had little to no effect on the Nanog expression levels (XREF_FIG)."
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"Through the screen they also found that USP21 significantly upregulated Nanog levels while other DUBs had little to no effect on the Nanog expression levels."
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"Moreover, depletion of USP21 by shRNAs in mESCs significantly increased the ubiquitination of endogenous Nanog (XREF_FIG), indicating that endogenous Nanog was also a target of USP21."
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"Recently, three groups independently identified ubiquitin specific peptidase 21 (USP21) as an efficient deubiquitylase that reverses Nanog polyubiquitylation and stabilizes Nanog protein."
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"[179] USP25 interacts with TRAF3 and TRAF6 following RNA virus or DNA virus infection and prevents TRAF3 and TRAF6 from proteasomal degradation via deubiquitinating K48 linked polyubiquitin chains."
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"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see XREF_SUPPLEMENTARY)."
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sparser
"Using immunoprecipitation assays we consistently observed that USP25 did not interact with TRAF6(C70A) or TRAF6(K124R) mutants, which cannot mediate self ubiquitination xref ( xref )."
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"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I and TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
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"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17."
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sparser
"In addition, we observed a weak, but detectable, direct association between USP25 and TRAF3 in pull-down assays in vitro, whereas we did not detect a direct interaction between USP25 and TRAF6 ( xref )."
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"In addition, we observed a weak, but detectable, direct association between USP25 and TRAF3 in pull-down assays in vitro, whereas we did not detect a direct interaction between USP25 and TRAF6 (XREF_SUPPLEMENTARY)."
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"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25.In recent years, USP25 has been extensively studied and some novel functions have been revealed."
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sparser
"USP25 interacts with TRAF6 through its UBA-UIM domains, and it deubiquitinates K 48 -linked chains from TRAF3 through its UCH-coil domains, which helps to maintain the cellular abundance of TRAF3 by inhibiting its degradation."
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"To test if USP25 recognizes ubiquitinated TRAF6 and deubiquitinates it, we reconstituted Usp25 -/- MEFs with empty vector, Flag tagged USP25 or USP25 (C178S) and examined IL-17-induced association between TRAF6 and USP25 or USP25 (C178S) in these cells."
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"Using antibodies to various TRAF for immunoprecipitation revealed that USP25 interacted with TRAF5 and TRAF6, but not with TRAF3 in HBECs or MEFs after IL-17 stimulation, while TNF stimulation induced neither USP25-TRAF5, USP25-TRAF6 nor USP25-TRAF3 association ( xref and data not shown)."
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sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
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"USP25 interacts with TRAF5 and TRAF6 and deubiquitinates Act1-mediated K63-linked ubiquitination of TRAF5 and TRAF6, thereby turning off IL-17 signaling."
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sparser
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1."
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sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6 and USP25 induced removal of Act1-mediated K63-linked ubiquitination in TRAF5 and TRAF6."
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sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6, and the USP25 deubiquitination activity opposed the activity of the Act1 E3 ubiquitin ligase, which ubiquitinates Lys63 in both TRAF5 and TRAF6."
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sparser
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
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sparser
"USP25 interacts with RIG-I and TRAF6. (A, B) HEK-293T cells grown in 100-mm dishes were co-transfected with the indicated plasmids encoding the RIG-I (A) or TRAF6 (B) expression vector (4 μg) and HA-USP25WT/ HA-USP25C178A/ HA-USP25H607A (4 μg) using Lipofectamine 2000."
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sparser
"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see Figure S1 )."
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"Upon infection with an RNA or DNA virus, USP25 associates with TRAF3 and TRAF6 and protects TRAF3 and TRAF6 from virus-induced proteasome-dependent or independent degradation ( xref )."
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"USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively."
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sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
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"Furthermore, we found that TRAF-USP25 interaction depended on Act1, as Act1 deficiency impaired their association ( xref ), indicating that Act1 was required for USP25 to engage TRAF5 and TRAF6 in the IL-17 pathway."
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"Act1 mediated K63 linked ubiquitination of TRAF6 was inhibited by overexpression of USP25, but not USP25 (C178S) in 293T cells or in an in vitro deubiquitination system (XREF_FIG and XREF_SUPPLEMENTARY)."
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"Therefore, USP25 may indirectly lead to deubiquitination of TRAF5 or TRAF6 through its tightly associated proteins."
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"However, Zhong et al. 's study using HEK293T cells supported deubiquitination of TRAF6 by USP25 [XREF_BIBR]."
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"Similarly, Usp25 deubiquitinates both TRAF5 and TRAF6 and thereby restricts downstream gene expression."
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"Mechanistically, USP25 deubiquitinated retinoic acid inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor mediated IFN signaling."
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act2."
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"In addition, wild-type USP25 significantly inhibits ubiquitination of RIG-I, TRAF2, and TRAF6, which is essential for activation of type I IFN signaling."
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"Taken together, our results demonstrate that USP25 negatively regulates IL-17-triggered ubiquitination of TRAF6 and TRAF5."
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"USP25 also deubiquitinated TRAF5 and TRAF6 to regulate in IL-17 signaling [XREF_BIBR]."
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"We observed that overexpression of USP25 significantly inhibited ubiquitination of RIG-I (XREF_FIG), TRAF2 (XREF_FIG), and TRAF6 (XREF_FIG)."
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"We observed that overexpression of USP25 significantly inhibited ubiquitination of RIG-I (Figure 7B), TRAF2 (Figure 7D), and TRAF6 (Figure 7E)."
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eidos
"] USP25 interacts with TRAF3 and TRAF6 following RNA virus or DNA virus infection and prevents TRAF3 and TRAF6 from proteasomal degradation via deubiquitinating K48-linked polyubiquitin chains ."
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"Several studies showed that USP25 negatively regulates virus-induced type I IFN signaling by stabilizing TRAF2, TRAF3 and TRAF6 [64,65,75,87,121,122,123,124]."
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"Act1 mediated K63 linked ubiquitination of TRAF6 was inhibited by overexpression of USP25, but not USP25 (C178S) in 293T cells or in an in vitro deubiquitination system (XREF_FIG and XREF_SUPPLEMENTARY)."
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"Furthermore, USP25 deficiency results in enhanced ubiquitination and turnover of TRAF6 and TRAF3."
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"It has been demonstrated recently that the cellular USP25 protein negatively regulates IL-17-mediated TRAF6 signaling by deubiquitinating TRAF6, and SYK mediated phosphorylation of USP25 alters cellular levels of USP25."
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"Our data showed that the interaction between USP21 and STING was markedly increased upon virus infection ( xref )."
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"Consistently, expression of RIG-I had little effect on interaction between USP21 and STING (XREF_FIG)."
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"Next, we examined whether the interaction between USP21 and STING is regulated by virus infection."
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"Our data showed that activation of p38 by coexpression of upstream kinase MKK3 or MKK6 enhanced the binding of USP21 to STING (XREF_FIG)."
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"On the other hand, blockage of p38 activation by SB202190 significantly inhibited both exogenous and endogenous interaction between USP21 and STING ( xref )."
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sparser
"Next, we examined whether p38 affects the HSV-1–induced binding of USP21 to STING."
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"Taken together, these data indicate that p38 mediated USP21 phosphorylation enhances the binding of USP21 to STING."
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"The phosphorylated USP21 in turn binds to STING and hydrolyzes K27/K63-linked polyubiquitination on STING."
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"Consistently, expression of RIG-I had little effect on interaction between USP21 and STING ( xref )."
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"USP21 can interact directly with STING and remove the K27 and K63 Ub chains on STING, thereby inhibiting the production of type I interferons."
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"The deubiquitinase USP21 can negatively regulate STING activity by removing K27- and K63 linked ubiquitin chains of STING [XREF_BIBR]."
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"Hence, at late stages of viral infection, p38-mediated phosphorylation of USP21 (Ubiquitin Specific Peptidase 21), a deubiquitinating enzyme, inhibits STING."
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"Our data showed that phosphorylation of USP21 by p38 promotes its binding to STING and inactivates STING in response to HSV-1 infection."
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"Our data showed that overexpression of USP21 blocked translocation of STING from ER to a perinuclear microsome upon HSV-1 infection (XREF_FIG)."
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"We found that prolonged DNA virus infection induces the phosphorylation of USP21 at Ser538 by activation of p38 MAPK, which in turn promotes the binding of USP21 to STING, deubiquitinates and inactivates STING."
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"Importantly, GST pull-down assay showed that phosphorylation of USP21 by activated p38 significantly enhanced the binding of USP21 to the purified STING (XREF_FIG)."
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"Our data indicated that microtubule association is not required for USP21 mediated STING inactivation (unpublished data)."
USP25 affects cell population proliferation
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USP25 activates cell population proliferation.
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USP25 activates cell population proliferation. 10 / 37
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"The expression of USP21 may promote proliferation, migration and invasion of breast cancer cells."
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"These data demonstrate that USP21 promotes cell proliferation via its deubiquitinating active site."
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"USP21 promotes cell proliferation and metastasis through suppressing EZH2 ubiquitination in bladder carcinoma."
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"In non small cell lung cancer, USP21 promotes tumor cell proliferation, migration, and invasion through the YY1 and SNHG16 axis."
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reach
"The expression of USP21 promoted DLBCL cell proliferation, while it had no obvious effect on cell death."
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reach
"Together, our findings demonstrated that USP21 promoted cell proliferation in BC."
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reach
"USP21 inhibition suppressed AMC-HN-8 and TU686 cell proliferation, migration and invasion."
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reach
"We reported that USP21 promoted GC cell proliferation, migration, invasion, and stemness in vitro, and regulated GC tumor growth and cell stemness in mice in vivo."
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reach
"We also showed that USP21 contributed to the progression of tumorigenesis by increasing proliferation, migration, and invasion."
USP25 inhibits cell population proliferation.
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USP25 inhibits cell population proliferation. 10 / 10
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"Knockdown of USP21 reduced the proliferation of MDA-MB-157 and MDA-MB-231 cells 5 days after siRNA transfection (XREF_FIG)."
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reach
"In addition, ectopic, doxycyclineinducible expression of FOXM1b in MDA-MB-231 cells partially rescued the impaired proliferation caused by USP21 depletion."
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reach
"As a result, siRNA mediated depletion of USP21 inhibits cell proliferation, invasion ability and decreases the CSCs percentage of RCC cell lines."
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reach
"USP21 is upregulated in renal cell carcinoma tissues and cell lines, and depletion of USP21 inhibits cell proliferation and invasion through binding to the IL-8 promoter region and mediating transcriptional initiation 22."
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reach
"Knockdown of USP21 in TNBC cells inhibited cell proliferation, migration and invasion."
✎
reach
"Several functional experiments, including colony formation analysis and CCK-8 analysis, suggested that overexpression of USP21 promoted cell proliferation and inhibition of USP21 suppressed cell proliferation."
✎
reach
"USP21 knockdown or overexpression in the DLBCL cell line shows that USP21 promotes cell proliferation."
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reach
"Accordingly, BCR-ABL-mediated signaling and cell proliferation were suppressed in BCR-ABL-positive leukemia cells by the depletion of USP25."
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reach
"Therefore, while depletion of USP21 (and FOXM1) impairs proliferation in each of these cell lines under control conditions, there is a statistically significant decrease in viability when USP21 depletion is combined with paclitaxel treatment."
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reach
"While cell proliferation rates were comparable at early time points examined, we found that USP21 depletion led to dramatically decrease of cell proliferation 6 days after transfection."
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reach
"USP25, a ubiquitin C-terminal hydrolase, also binds to Syk in a phosphotyrosine independent manner [XREF_BIBR]."
✎
reach
"As shown in Fig. 4, forced LYN kinase expression did not however alter the USP25 and SYK interaction, further suggesting that the presence of a phosphotyrosine residue is not required for this peculia[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
sparser
"These results demonstrate that USP25 specifically interacts with SYK and suggest that the binding determinants are not conserved in their respective paralogs."
✎
sparser
"Mapping of the interacting domains on USP25 and SYK is summarized in Fig. 3 B.
Our data also demonstrate that the SYK–USP25 interaction occurs in the absence of the kinase domain of SYK."
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reach
"These results demonstrate that USP25 specifically interacts with SYK and suggest that the binding determinants are not conserved in their respective paralogs.To determine whether USP25 binds to SYK in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
reach
"Thus, USP25 and tensin2 bind Syk by different mechanisms and do not share a common binding site."
✎
sparser
"Thus, USP25 and tensin2 bind Syk by different mechanisms and do not share a common binding site."
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reach
"As shown in Fig. 5 B (first panel), the SYK dependent phosphorylation of USP25 was inhibited by Piceatannol in a dose dependent manner."
✎
sparser
"Altogether, these data strengthen our results that SYK specifically phosphorylates USP25 and suggest that Y740 is the most probable phosphorylated tyrosine on USP25."
✎
sparser
"As previously shown, SYK-dependent phosphorylation of immunoprecipitated USP25 was inhibited by Piceatannol treatment ( Fig. 6 A , First panel, compare lanes 2 to 3)."
✎
sparser
"On the other hand, SYK-dependent phosphorylation of USP25 does not lead to its proteasomal degradation."
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reach
"The USP25 protease activities measured in cells treated or not with Piceatannol were not significantly different suggesting that Syk dependent phosphorylation of USP25 had no effect on the proteolytic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
rlimsp
"Moreover, we showed that SYK specifically phosphorylates USP25 and alters its cellular levels."
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sparser
"Moreover, we showed that SYK specifically phosphorylates USP25 and alters its cellular levels suggesting a novel mechanism for USP25 regulation by posttranslational modifications similar to the recent[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"To confirm that USP25 phosphorylation as well as regulation of USP25 intracellular levels are mediated by SYK kinase activity, we analyzed the phosphorylation status and expression levels of USP25 in [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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reach
"As shown in Fig. 5 C, USP25 but not USP28 was phosphorylated in the presence of overexpressed SYK indicating that SYK selectivity phosphorylates USP25."
✎
sparser
"Additional studies are needed to investigate the functional consequence(s) of USP25 phosphorylation by SYK, the molecular mechanism(s) by which SYK alters the intracellular levels of USP25 and whether[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
sparser
"For instance, SYK-dependent phosphorylation of USP25 at residue Tyr740 can sharply reduce its protein levels."
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reach
"Altogether, these data strengthen our results that SYK specifically phosphorylates USP25 and suggest that Y740 is the most probable phosphorylated tyrosine on USP25.We also assessed whether the SYK me[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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reach
"The SYK non-receptor tyrosine kinase can specifically phosphorylate USP25 and decrease its cellular levels ."
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sparser
"Our data showed that the interaction between USP21 and STING was markedly increased upon virus infection ( xref )."
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reach
"Consistently, expression of RIG-I had little effect on interaction between USP21 and STING (XREF_FIG)."
✎
sparser
"Next, we examined whether the interaction between USP21 and STING is regulated by virus infection."
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reach
"Our data showed that activation of p38 by coexpression of upstream kinase MKK3 or MKK6 enhanced the binding of USP21 to STING (XREF_FIG)."
✎
sparser
"On the other hand, blockage of p38 activation by SB202190 significantly inhibited both exogenous and endogenous interaction between USP21 and STING ( xref )."
✎
sparser
"Next, we examined whether p38 affects the HSV-1–induced binding of USP21 to STING."
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reach
"Taken together, these data indicate that p38 mediated USP21 phosphorylation enhances the binding of USP21 to STING."
✎
sparser
"The phosphorylated USP21 in turn binds to STING and hydrolyzes K27/K63-linked polyubiquitination on STING."
✎
sparser
"Consistently, expression of RIG-I had little effect on interaction between USP21 and STING ( xref )."
✎
reach
"USP21 can interact directly with STING and remove the K27 and K63 Ub chains on STING, thereby inhibiting the production of type I interferons."
✎
reach
"To investigate whether USP21 interacts with Nanog, co-immunoprecipitation assays were performed."
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reach
"Here we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs)."
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reach
"Taken together, the results indicate that USP21 can interact with Nanog both in vivo and in vitro."
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reach
"The K to R mutations did not affect the interaction between USP21 and Nanog (XREF_SUPPLEMENTARY), suggesting that binding of USP21 was independent of Nanog ubiquitination."
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sparser
"This phosphorylation reduced the binding of USP21 to Nanog and led to Nanog degradation."
✎
sparser
"Moreover, activation of ERK1 by co-expression of a constitutively active MEK1 (MEK1 CA ) in HEK293T cells significantly impaired the interaction between USP21 and Nanog ( xref )."
✎
sparser
"In this study, we have identified a novel deubiquitinating enzyme USP21 which interacts with NANOG by both yeast two hybrid screening for DUBs and immunoprecipitation analyses."
✎
sparser
"This phosphorylation reduced the binding of USP21 to Nanog and led to Nanog degradation."
✎
sparser
"USP21 directly interacts with NANOG through its ubiquitin carboxyl-terminal hydrolase domain (UCH), and the phosphorylation of USP21 by ERK1 prevents this binding, leaving this site exposed for ubiquitination, ultimately leading to NANOG degradation by the UPS ( xref )."
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reach
"Furthermore, treatment of mESCs with FGF4 reduced the interaction between Nanog and USP21 in mESCs in a manner that could be reversed by the MEK inhibitor PD0325901 (XREF_FIG)."
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reach
"Interestingly, we also noticed that co-expression of MEK1 CA and ERK resulted in the band shift of both Nanog and USP21 (XREF_SUPPLEMENTARY), which is possibly caused by the phosphorylation of Nanog and USP21 by the activated ERK."
✎
reach
"Moreover, depletion of USP21 by shRNAs in mESCs significantly increased the ubiquitination of endogenous Nanog (XREF_FIG), indicating that endogenous Nanog was also a target of USP21."
✎
sparser
"Although USP25 interacted with TRAF3 constitutively in overexpression system in 293T cells, IL-17 treatment did not induce USP25-TRAF3 association in HBECs or MEFs."
✎
sparser
"Therefore, the interaction between USP25 and TRAF3 eliminates K48-linked polyubiquitin chains from TRAF3 and causes ET."
✎
reach
"However, the signals that stimulate an association between USP25 and TRAF3 are unknown."
✎
sparser
"Because USP25 interacted with TRAF3 after stimulation with LPS and because the enzyme activity of USP25 was required for its regulation of TLR4 signaling ( xref and xref ), we hypothesized that USP25 might target TRAF3 for deubiquitination in response to LPS."
✎
reach
"Because USP25 interacted with TRAF3 after stimulation with LPS and because the enzyme activity of USP25 was required for its regulation of TLR4 signaling (XREF_FIG and XREF_FIG), we hypothesized that USP25 might target TRAF3 for deubiquitination in response to LPS."
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reach
"We found that stimulation with LPS or Pam 3 CSK 4, but not poly (I : C), promoted an association between USP25 and TRAF3 (XREF_FIG)."
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reach
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17."
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reach
"Although USP25 interacted with TRAF3 constitutively in overexpression system in 293T cells, IL-17 treatment did not induce USP25-TRAF3 association in HBECs or MEFs."
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reach
"[179] USP25 interacts with TRAF3 and TRAF6 following RNA virus or DNA virus infection and prevents TRAF3 and TRAF6 from proteasomal degradation via deubiquitinating K48 linked polyubiquitin chains."
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reach
"These data suggest that LPS stimulates the recruitment of USP25 and TRAF3 to the TLR4 signaling complex in which USP25 interacts with TRAF3."
✎
sparser
"Upon infection with an RNA or DNA virus, USP25 associates with TRAF3 and TRAF6 and protects TRAF3 and TRAF6 from virus-induced proteasome-dependent or independent degradation ( xref )."
✎
sparser
"USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
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reach
"Therefore, the interaction between USP25 and TRAF3 eliminates K48 linked polyubiquitin chains from TRAF3 and causes ET."
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reach
"Taking it one step further, Lin et al. uncovered that USP25 stabilizes TRAF3 in a DUB activity dependent manner by deubiquitinating K48-Ub of TRAF3 in bone marrow-derived macrophages (BMDM) cells, inhibiting TLR4 signaling-induced innate immune responses [21]."
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reach
"We mentioned in a previous section that USP25 deubiquitinates TRAF3 and interacts with TRAF6, increasing expression of Tnf in HEK293 T cells [21,22], while in MEF cells, USP25 negatively affects TNF-α-induced NF-κB activation [20]."
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reach
"Because the activation of TLR4 results in the K 48 -linked ubiquitination and degradation of TRAF3, we next determined the effects of a deficiency in USP25 on the LPS induced ubiquitination and degradation of TRAF3."
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reach
"We mentioned in a previous section that USP25 deubiquitinates TRAF3 and interacts with TRAF6, increasing expression of Tnf in HEK293T cells [XREF_BIBR, XREF_BIBR], while in MEF cells, USP25 negatively affects TNF-alpha-induced NF-kappaB activation [XREF_BIBR]."
"Ubiquitin-specific protease 25 regulates TLR4-dependent innate immune responses through deubiquitination of the adaptor protein TRAF3"
✎
reach
"Induction of USP25 by viral infection promotes innate antiviral responses by mediating the stabilization of TRAF3 and TRAF6."
✎
reach
"Because USP25 interacted with TRAF3 after stimulation with LPS and because the enzyme activity of USP25 was required for its regulation of TLR4 signaling (XREF_FIG and XREF_FIG), we hypothesized that USP25 might target TRAF3 for deubiquitination in response to LPS."
✎
reach
"Thus, by inhibiting the degradation of TRAF3 during TLR4 activation, USP25 enables a balanced innate immune response."
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reach
"Furthermore, USP25 deficiency results in enhanced ubiquitination and turnover of TRAF6 and TRAF3."
✎
reach
"Deficiency in USP25 in mice potentiated LPS induced degradative ubiquitination of TRAF3, which led to enhanced production of proinflammatory cytokines and impaired production of type I IFNs."
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reach
"Deficiency in USP25 enhanced the extent of ubiquitination of TRAF3 and accelerated its degradation after TLR4 activation, which potentiated TLR4 induced activation of NF-kappaB (nuclear factor kappaB) and MAPK (mitogen activated protein kinase) signaling, but inhibited activation of the transcription factor IRF3 (interferon regulatory factor 3)."
✎
eidos
"] USP25 interacts with TRAF3 and TRAF6 following RNA virus or DNA virus infection and prevents TRAF3 and TRAF6 from proteasomal degradation via deubiquitinating K48-linked polyubiquitin chains ."
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reach
"Several studies showed that USP25 negatively regulates virus-induced type I IFN signaling by stabilizing TRAF2, TRAF3 and TRAF6 [64,65,75,87,121,122,123,124]."
✎
reach
"We found overexpression of USP25 indeed decreased TRAF3 K48 linked ubiquitination."
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reach
"A series of in vitro experiments testified that USP21 regulated the expression of MAPK1 by binding to transcription factor GATA3, thereby regulating the tumor growth and cell stemness of GC."
✎
sparser
"In agreement with this previous study, we confirmed the endogenous interaction between USP21 and GATA3 in human expanding Treg cells ( xref )."
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reach
"In agreement with this previous study, we confirmed the endogenous interaction between USP21 and GATA3 in human expanding Treg cells (XREF_SUPPLEMENTARY)."
✎
reach
"Here, we show how USP21 interacts with and stabilizes GATA3 by mediating its deubiquitination."
✎
reach
"In order to further explore possible functional interactions between USP21 and GATA3, we carried out an in depth characterization of hematopoiesis and lymphocyte differentiation in the Usp21 -/- mice."
✎
sparser
"In Tregs, FOXP3 binds to the promoter region of USP21 and activates its transcription, and USP21 interacts with GATA3 and deubiquitinates it, thus inhibiting its degradation by the proteasome and maintaining its stability."
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reach
"Zhang et al. have reported that in Treg cells, the DUB USP21 interacted with and stabilized GATA3 via deubiquitination with the overexpression of USP21 obviously decreasing the ubiquitination status of GATA3."
✎
sparser
"This work proposes that in Tregs, USP21, GATA3, and FOXP3 may form a positive loop to promote FOXP3 expression and thus modulate Treg activity."
✎
sparser
"Thus, USP21, GATA3, and FOXP3 could form a positive loop in promoting FOXP3 expression that in turns modulates Treg cell activity ( xref )."
✎
reach
"USP21 positively regulates and stabilizes GATA3, which can maintain FOXP3 expression."
✎
reach
"In a search for DUBs that contribute to GATA3 stabilization in FOXP3-expressing cells, both USP7 and USP21 were shown to upregulate GATA3-mediated activity using a reporter assay ."
✎
reach
"Interestingly, Foxp3 directly activates expression of USP21, and siRNA knockdown of USP21 downregulates both GATA3 and Foxp3 protein."
✎
reach
"Overexpression of USP21 can rescue GATA3 from its degradation so as to stabilize the expression of GATA3 [XREF_BIBR]; RT-PCR showed that the mRNA of USP21 is upregulated in the Treg cells of asthma patients."
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reach
"In a search for DUBs that contribute to GATA3 stabilization in FOXP3-expressing cells, both USP7 and USP21 were shown to upregulate GATA3-mediated activity using a reporter assay 131 ."
✎
reach
"In summary, we have identified a USP21 mediated pathway that promotes GATA3 stabilization and expression at the post-translational level."
✎
reach
"Furthermore, USP21 also deubiquitinates GATA3, a transcription factor which limit T reg induced pro inflammatory responses, and its expression was noted to be upregulated in asthmatic patients."
✎
reach
"Recent reports demonstrate that GATA3 can be deubiquitinated by Usp21 which rescues it from proteosomal degradation and stabilises GATA3 protein levels [XREF_BIBR]."
✎
reach
"For example, USP21 can mediate deubiquitination of GATA3 and maintain GATA3 expression in regulatory T cells."
✎
reach
"Another DUB, USP21, which is itself activation induced, interacts with and deubiquitinates GATA3 to stabilize its expression in cell lines and primary human Tregs."
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sparser
"Results from IP directed against both Myc-FOXM1b ( xref ) and FLAG-HA-USP21 ( xref ) demonstrate that USP21 binds to a region encompassing FOXM1 amino acids 321–400."
✎
reach
"An interaction between FOXM1 and USP21 was detected by coimmunoprecipitation (co-IP), regardless of whether the immuno precipitation (IP) was directed against Myc-USP21 (XREF_FIG) or HA-FOXM1b (XREF_FIG)."
✎
reach
"reveal that USP21 directly binds to FOXM1, makes it deubiquitinate, and increases its expression level in vitro and in vivo."
✎
reach
"Because USP21 can directly bind and deubiquitinate FOXM1, we next evaluated the impact of USP21 on FOXM1 stability."
✎
reach
"USP21 increases the stability of FOXM1, and USP21 binds and deubiquitinates FOXM1 in vivo and in vitro, indicating a direct enzyme-substrate relationship."
✎
sparser
"Because USP21 can directly bind and deubiquitinate FOXM1, we next evaluated the impact of USP21 on FOXM1 stability."
✎
sparser
"In addition, an interaction between endogenous FOXM1 and USP21 was detected using antibodies directed against USP21 ( xref )."
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reach
"In addition, an interaction between endogenous FOXM1 and USP21 was detected using antibodies directed against USP21 (XREF_FIG)."
✎
sparser
"Arceci et al. reveal that USP21 directly binds to FOXM1, makes it deubiquitinate, and increases its expression level in vitro and in vivo ."
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reach
"The expression of USP21 WT increased FOXM1 stability, and its half-life was approximately 12.4 h."
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reach
"This is consistent with our previous data demonstrating that FOXM1 abundance is positively enhanced by USP21 overexpression."
✎
reach
"These findings proved that USP21 promoted tumor growth and cancer cell stemness in nasopharyngeal carcinoma by regulating FOXM1."
✎
reach
"USP21 increases the stability of FOXM1, and USP21 binds and deubiquitinates FOXM1 in vivo and in vitro, indicating a direct enzyme-substrate relationship."
✎
reach
"USP21 stabilizes FOXM1, and suppressing USP21 reduces FOXM1 abundance, which subsequently downregulates the FOXM1 transcriptional network."
✎
reach
"Correspondingly, ectopic expression of USP21 significantly increased FOXM1 abundance in 293T cells (XREF_FIG)."
✎
reach
"USP21 overexpression significantly enhanced FOXM1 dependent transcriptional activity compared with control (XREF_FIG)."
✎
reach
"Because FOXM1 is upregulated by USP21, we asked whether a curated list of 114 FOXM1 target genes is correlated with USP21 amplification using gene set enrichment analysis (GSEA)."
✎
reach
"HDACi treatment increased the ubiquitination level of FOXM1 by suppressing ubiquitin-specific peptidase 21 (USP21), which deubiquitinates FOXM1."
✎
reach
"FOXM1 Deubiquitination by USP21 Regulates Cell Cycle Progression and Paclitaxel Sensitivity in Basal like Breast Cancer."
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reach
"Similarly, USP21 WT, but not USP21 C221A, immunopurified from 293T cells reduced polyubiquitination of FOXM1 isolated from proteasome inhibitor treated 293T cells in an in vitro deubiquitination assay (XREF_SUPPLEMENTARY)."
✎
reach
"USP21 increases the stability of FOXM1, and USP21 binds and deubiquitinates FOXM1 in vivo and in vitro, indicating a direct enzyme-substrate relationship."
✎
reach
"Then, the western blot assays indicated that knockdown of USP21 in nasopharyngeal carcinoma cells would inhibit FOXM1 expression, and overexpression of FOXM1 could reverse the cell proliferation ability, cell migration and invasion ability, and cell stemness profiles."
✎
reach
"IB analysis of cell lysates 48 h after transfection revealed that USP21 knockdown reproducibly reduced the level of endogenous FOXM1 (XREF_FIG)."
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reach
"Both USP21 and A20 inhibited SeV- and RIG-I-CARD-induced IFN-beta reporter activity in a dose dependent manner."
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reach
"Interestingly, we found that overexpression of USP21 WT but not C221A mutant inhibited IFN-beta, NF-kappaB, and ISRE reporter activities in HEK293T cells in response to transfected poly (I : C), which was known to be mediated by MDA5 (unpublished data), suggesting that USP21 might also target MDA5."
✎
reach
"Cellular ubiquitin specific proteases, USP21, USP3 and USP15, a subfamily of deubiqutinase, remove K63 linked polyubiquitin chains from RIG-I and block it to induce IFN-beta."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β (Figure 6A), IRF3 (Figure 6B), NF-κB (Figure 6C) and ISRE (Figure 6D) in a dose-dependent manner."
✎
reach
"Reporter assays then indicated that knockdown of USP25 markedly potentiated SEV induced activation of the IFN-beta promoter (XREF_FIG)."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"USP21 also inhibited RIG-I-CARD-induced IFN-beta reporter activity in WT, A20 -/-, ITCH -/-, and TAXBP1 -/- MEFs (unpublished data)."
✎
reach
"In this screening, USP18 and USP21 significantly inhibited RIG-I-CARD-induced IFN-beta reporter activity, whereas other USPs had no effect or fewer effects (XREF_FIG)."
✎
reach
"Fan et al., knowing that USP21 inhibits RIG-I-induced IFN-beta production, searched for its mechanism [XREF_BIBR]."
✎
reach
"Overexpression studies in HEK293T cells revealed that USP21 might also bind and deubiquitinate MDA5 by removing K63 linked polyubiquitination, thus inhibiting IFN-beta, NF-kappaB, and IFN stimulated response element (ISRE) reporter activities."
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reach
"Our data showed that Usp21 knockdown significantly enhanced Ifnb expression in WT but not in Sting -/- MEFs (XREF_FIG)."
✎
reach
"Taken together, our results suggest that USP25 negatively regulates IFN-β expression by inhibiting SEV-induced activation of IRF3 and NF-κB.USPs are cysteine proteases that vary greatly in size and structural complexity."
✎
reach
"Taken together, our results suggest that USP25 negatively regulates IFN-beta expression by inhibiting SEV induced activation of IRF3 and NF-kappaB."
✎
reach
"We found that knockdown of Usp21 in mouse fibroblast L929 cells significantly enhanced the expression of Ifnb, Ifna4, and Isg15 (XREF_FIG)."
✎
sparser
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent
To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"Notably, Usp21 fl/fl Lyz2-cre mice produced significantly higher concentrations of IFNbeta, IL-6, and TNF in serum upon HSV-1 infection compared with infected control mice (XREF_FIG)."
✎
reach
"Furthermore, Knockdown of USP25 potentiated virus induced induction of the IFN-beta."
✎
reach
"Consistently, Usp21 deficiency resulted in production of more IFNbeta and TNF in MEFs and BMDMs in response to HSV-1 infection (XREF_FIG)."
✎
reach
"Usp21 ablation also drastically enhanced the expression of Ifnb, Ifna4, or TNF mRNA in primary PEMs (peritoneal macrophages; XREF_FIG) or BMDMs (BM derived macrophages; XREF_FIG)."
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reach
"USP25 's DUB activity was also found to be necessary for virus induced signaling, as USP25 knockdown MEFs with WT USP25 reconstitution allowed expression of Ifnb, Ifna4 and IL-6 upon SeV or HSV-1 induction, while those with DUB activity mutant USP25 did not [XREF_BIBR]."
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reach
"We next expressed and purified His USP21, MBP and MBP-FOXP3 from Escherichia coli, and carried out an in vitro MBP pulldown assay that confirmed the direct interaction between FOXP3 and USP21 (XREF_FIG)."
✎
reach
"Reciprocal immunoprecipitation of FLAG-FOXP3 and Myc-USP21 revealed an interaction between USP21 and FOXP3 (XREF_FIG), and we also detected the endogenous interaction between USP21 and FOXP3 in human Treg cells (XREF_FIG)."
✎
sparser
"In Tregs, FOXP3 binds to the promoter region of USP21 and activates its transcription, and USP21 interacts with GATA3 and deubiquitinates it, thus inhibiting its degradation by the proteasome and maintaining its stability."
✎
sparser
"Furthermore, we found that FOXP3 could directly bind to the USP21 gene promoter and activated its transcription upon TcR stimulation."
✎
sparser
"We next expressed and purified His-USP21, MBP and MBP-FOXP3 from Escherichia coli , and carried out an in vitro MBP pulldown assay that confirmed the direct interaction between FOXP3 and USP21 ( xref )."
✎
sparser
"Reciprocal immunoprecipitation of FLAG-FOXP3 and Myc-USP21 revealed an interaction between USP21 and FOXP3 ( xref ), and we also detected the endogenous interaction between USP21 and FOXP3 in human Treg cells ( xref )."
✎
reach
"To test whether USP21 is a direct E3 deubiquitinase of FOXP3 that prevents its degradation, we first carried out binding studies to determine whether FOXP3 could directly bind to USP21."
✎
sparser
"This work proposes that in Tregs, USP21, GATA3, and FOXP3 may form a positive loop to promote FOXP3 expression and thus modulate Treg activity."
✎
sparser
"Thus, USP21, GATA3, and FOXP3 could form a positive loop in promoting FOXP3 expression that in turns modulates Treg cell activity ( xref )."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [ xref ]."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [111]."
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reach
"Here USP21 prevents FOXP3 degradation most likely through removing K48 linked polyubiquitin moieties."
✎
reach
"Interestingly, Foxp3 directly activates expression of USP21, and siRNA knockdown of USP21 downregulates both GATA3 and Foxp3 protein."
✎
reach
"USP21 prevents FOXP3 degradation through deubiquination, thus stabilizing Treg phenotype and antagonizing the development of Th1 like Tregs [XREF_BIBR]."
✎
reach
"Similarly, USP21 prevents Foxp3 degradation by deubiquitinating K48-type modifications at residues Lys 206, Lys 216, Lys 227, Lys 252, Lys 277, Lys 332, and Lys 393."
✎
reach
"Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo."
✎
reach
"Therefore, these results support that USP21 prevents FOXP3 depletion in Treg cells through deubiquitination and protection from ubiquitination mediated protein degradation."
✎
reach
"Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells."
✎
reach
"Taken together, our results show that USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo."
✎
reach
"In previous studies, we showed that Foxp3 could be ubiquitinated and degraded by the E3 ubiquitin ligase Stub1 (STIP1 homology and U-Box containing protein 1) or deubiquitinated and stabilized by the deubiquitinase USP21 (ubiquitin specific peptidase 21) (Chen et al., 2013; Yang et al., 2015; Li et al., 2016)."
USP25 affects Interferon
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USP25 inhibits Interferon.
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USP25 inhibits Interferon. 10 / 18
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reach
"We further investigated the effect of USP25 knockdown on virus triggered IFN signaling."
✎
reach
"Collectively, these findings suggest that USP25 inhibits RIG-I and MDA5-dependent type I IFN signaling."
✎
reach
"However, the catalytic mutants (C178A and H607A) devoid of DUB activity lost the ability of USP25 WT-mediated IFN inhibition to some degree, indicating that DUB activity is involved in USP25 inhibition of type I IFN induction.Sequence for siRNAs of human USP25."
✎
reach
"doi: 10.1371/journal.pone.0080976.g005 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org 7B), TRAF2 (Figure 7D), and TRAF6 (The deubiquitinating activity of USP25 is involved in virus-induced type I IFN signaling."
✎
reach
"*P < 0.05 for all pairwise comparisons by one-way ANOVA followed by Dunnett's multiple comparisons test.doi: 10.1371/journal.pone.0080976.g006 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.orgUSP25 deubiquitinates RIG-I, TRAF2 and TRAF6."
✎
reach
"To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-beta-Luc."
✎
reach
"To examine whether the inhibitory effects of USP25 on SEV induced type I IFN signaling is due to its deubiquitinase activity, wild-type USP25 (USP25-WT) and its mutants (C178A and H607A) lacking DUB activity were co-transfected with the promoter luciferase reporter plasmid of IFN-beta, IRF3, NF-kappaB and ISRE, and the luciferase activity was detected."
✎
reach
"In addition, USP25 deficiency inhibits transcriptional activity of interferon regulatory factor, thereby reducing type I interferon production."
| PMC
✎
reach
"However, the catalytic mutants (C178A and H607A) devoid of DUB activity lost the ability of USP25 WT-mediated IFN inhibition to some degree, indicating that DUB activity is involved in USP25 inhibition of type I IFN induction.To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"Several studies showed that USP25 negatively regulates virus-induced type I IFN signaling by stabilizing TRAF2, TRAF3 and TRAF6 [64,65,75,87,121,122,123,124]."
USP25 bound to K63 and IFIH1 inhibits Interferon. 1 / 1
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1
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reach
"Overexpression studies in HEK293T cells revealed that USP21 might also bind and deubiquitinate MDA5 by removing K63 linked polyubiquitination, thus inhibiting IFN-beta, NF-kappaB, and IFN stimulated response element (ISRE) reporter activities."
USP25 activates Interferon.
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USP25 activates Interferon. 7 / 7
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6
✎
reach
"Intraperitoneal injection of VSV in 4-wk-old USP21 -/- also induced a stronger IFN production compared with that in 4-wk-old WT mice (unpublished data)."
✎
reach
"Mutation of the catalytic residues results in significant loss of ability of USP25 mediated IFN inhibition."
✎
reach
"USP25 restricts proinflammatory cytokine production and promotes type I IFN production upon LPS stimulation."
✎
reach
"However, our studies explain that USP25 negatively modulates RIG-I/MDA5-dependent type I IFN signaling."
✎
eidos
"In addition , USP25 deficiency inhibits transcriptional activity of interferon regulatory factor , thereby reducing type I interferon production ( 20 ) ."
| PMC
✎
reach
"However, our studies explain that USP25 negatively modulates RIG-I and MDA5-dependent type I IFN signaling."
✎
reach
"Some of the reported mechanisms include regulation of suppressor of cytokine signaling 3-Phosphorylated signal transducer and activator of transcription 3, Wnt pathway/β-catenin, and NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathways.27, 28, 30 29 A recent report showed that USP25 inhibited Toll-like receptor 4 (TLR4)-triggered proinflammatory signaling and promoted type I interferon signaling through deubiquitination of tumor necrosis factor receptor–associated factor (TRAF)3."
USP25 increases the amount of Interferon.
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USP25 increases the amount of Interferon. 1 / 1
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✎
reach
"Several other DUBs have also been implicated in the regulation of RIG-I ubiquitination and virus induced type I IFN expression; these include A20, USP3, USP15, USP21, and USP25 XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
USP25 deubiquitinates Interferon.
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Modified USP25 leads to the deubiquitination of Interferon. 1 / 1
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✎
reach
"Overexpression of USP21 inhibited RNA virus induced RIG-I polyubiquitination and RIG-I-mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-alpha and beta production, and antiviral responses in MEFs in response to RNA virus infection."
✎
reach
"Consistent with our model, we demonstrate a direct interaction between USP25 and TNKS in adipocytes, both of which cofractionate with a subpopulation of internal GLUT4 containing membranes."
✎
reach
"Binding of both USP25 and IRAP to TNKS in adipocytes could serve to recruit USP25 to GSVs."
✎
sparser
"We show that C44 disrupts the interaction between TNKS and USP25 leading to a higher half-life of AXIN and the breakdown of <beta>-catenin protein."
✎
reach
"The effect of disruption of the interaction between TNKS and USP25 by small molecules on prostate cancer proliferation is unknown."
✎
sparser
"The effect of disruption of the interaction between TNKS and USP25 by small molecules on prostate cancer proliferation is unknown."
✎
reach
"We show that C44 disrupts the interaction between TNKS and USP25 leading to a higher half-life of AXIN and the breakdown of <beta>-catenin protein."
✎
sparser
"The analysis led to the discovery that the small molecule C44 disrupted the interaction between TNKS and USP25, leading to an increase in the half-life of axin, which in turn regulated the Wnt/β-catenin pathway."
✎
sparser
"The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes."
✎
sparser
"In addition, the ubiquitin-specific protease USP25 antagonizes Wnt signaling by promoting deubiquitination and stabilization of PARP5a/b, and disruption of PARP5a interaction with USP25 destabilizes PARP5a/b, leading to Axin1/2 stabilization and subsequent attenuation of Wnt signaling [ xref ]."
✎
sparser
"Here we demonstrate that USP25 and Tankyrase interact, and colocalise with GLUT4 in insulin-sensitive cells."
USP25 affects Neoplasm Invasiveness
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USP25 activates Neoplasm Invasiveness.
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USP25 activates Neoplasm Invasiveness. 10 / 17
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reach
"USP21 inhibition suppressed AMC-HN-8 and TU686 cell proliferation, migration and invasion."
✎
reach
"The expression of USP21 may promote proliferation, migration and invasion of breast cancer cells."
✎
reach
"Thus far, a study proved that USP21 can accelerate cell growth, invasion, and stemness of renal cell carcinoma."
✎
reach
"USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination."
✎
reach
"XREF_BIBR, XREF_BIBR Recently, one report indicated that USP21 promotes cell proliferation and invasion ability in human renal cell carcinoma."
✎
reach
"To further show the importance of this protein in cellular invasion, knockdown of USP25 significantly reduced cell invasion and its overexpression increased cell invasion as assayed by transwell invasion assays."
✎
reach
"Afterward, the role of USP21 in cell migration and invasion was evaluated through Transwell assay, and the data in XREF_FIG showed that overexpression of USP21 accelerated the migration and invasion of AGS cells, whereas knockdown of USP21 pronouncedly reduced the migration and invasion of MKN-45 cells."
✎
reach
"These results demonstrated that USP21 stimulated cell proliferation, migration, invasion, and stemness of GC cells."
USP25 inhibits Neoplasm Invasiveness.
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USP25 inhibits Neoplasm Invasiveness. 6 / 6
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✎
reach
"USP21 is upregulated in renal cell carcinoma tissues and cell lines, and depletion of USP21 inhibits cell proliferation and invasion through binding to the IL-8 promoter region and mediating transcriptional initiation 22."
✎
reach
"Knockdown of USP25 by siRNA in A549, H1299, and SPC-A-1sci cells inhibited cell migration and invasion in vitro, which fell to levels similar to those observed after transfection with the miR-200c mimics."
✎
reach
"Knockdown of USP21 in TNBC cells inhibited cell proliferation, migration and invasion."
✎
reach
"Knockdown of USP21 decreased the cell growth, invasion and cancer stem cell percentage of A-704 cells."
✎
reach
"The miR-27a-3p/USP25 axis was observed to inhibit trophoblast migration and invasion in the pathogenesis of RSA (Zhao et al., 2017)."
✎
reach
"Knockdown of USP21 decreased the cell growth, invasion and cancer stem cell percentage of 786-O cells."
USP25 inhibits Neoplasm Invasiveness. 2 / 2
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2
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reach
"Histologic analysis and subsequent injury scoring showed that Usp25 deficiency increases edema and inflammatory cell infiltration after cerulein administration compared with mice with intact Usp25 (Figure 8B and C)."
✎
reach
"Usp25 deficiency exacerbated pancreatic and lung injury induced by L-arginine, cerulein, and CDE, and increased neutrophil and macrophage infiltration and systemic inflammatory responses."
✎
reach
"[179] USP25 interacts with TRAF3 and TRAF6 following RNA virus or DNA virus infection and prevents TRAF3 and TRAF6 from proteasomal degradation via deubiquitinating K48 linked polyubiquitin chains."
✎
reach
"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see XREF_SUPPLEMENTARY)."
✎
sparser
"Using immunoprecipitation assays we consistently observed that USP25 did not interact with TRAF6(C70A) or TRAF6(K124R) mutants, which cannot mediate self ubiquitination xref ( xref )."
✎
reach
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I and TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
✎
reach
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17."
✎
sparser
"In addition, we observed a weak, but detectable, direct association between USP25 and TRAF3 in pull-down assays in vitro, whereas we did not detect a direct interaction between USP25 and TRAF6 ( xref )."
✎
reach
"In addition, we observed a weak, but detectable, direct association between USP25 and TRAF3 in pull-down assays in vitro, whereas we did not detect a direct interaction between USP25 and TRAF6 (XREF_SUPPLEMENTARY)."
✎
reach
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25.In recent years, USP25 has been extensively studied and some novel functions have been revealed."
✎
sparser
"USP25 interacts with TRAF6 through its UBA-UIM domains, and it deubiquitinates K 48 -linked chains from TRAF3 through its UCH-coil domains, which helps to maintain the cellular abundance of TRAF3 by inhibiting its degradation."
✎
reach
"To test if USP25 recognizes ubiquitinated TRAF6 and deubiquitinates it, we reconstituted Usp25 -/- MEFs with empty vector, Flag tagged USP25 or USP25 (C178S) and examined IL-17-induced association between TRAF6 and USP25 or USP25 (C178S) in these cells."
✎
sparser
"Using antibodies to various TRAF for immunoprecipitation revealed that USP25 interacted with TRAF5 and TRAF6, but not with TRAF3 in HBECs or MEFs after IL-17 stimulation, while TNF stimulation induced neither USP25-TRAF5, USP25-TRAF6 nor USP25-TRAF3 association ( xref and data not shown)."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"USP25 interacts with TRAF5 and TRAF6 and deubiquitinates Act1-mediated K63-linked ubiquitination of TRAF5 and TRAF6, thereby turning off IL-17 signaling."
✎
sparser
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6 and USP25 induced removal of Act1-mediated K63-linked ubiquitination in TRAF5 and TRAF6."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6, and the USP25 deubiquitination activity opposed the activity of the Act1 E3 ubiquitin ligase, which ubiquitinates Lys63 in both TRAF5 and TRAF6."
✎
sparser
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
✎
sparser
"USP25 interacts with RIG-I and TRAF6. (A, B) HEK-293T cells grown in 100-mm dishes were co-transfected with the indicated plasmids encoding the RIG-I (A) or TRAF6 (B) expression vector (4 μg) and HA-USP25WT/ HA-USP25C178A/ HA-USP25H607A (4 μg) using Lipofectamine 2000."
✎
sparser
"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see Figure S1 )."
✎
sparser
"Upon infection with an RNA or DNA virus, USP25 associates with TRAF3 and TRAF6 and protects TRAF3 and TRAF6 from virus-induced proteasome-dependent or independent degradation ( xref )."
✎
sparser
"USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"Furthermore, we found that TRAF-USP25 interaction depended on Act1, as Act1 deficiency impaired their association ( xref ), indicating that Act1 was required for USP25 to engage TRAF5 and TRAF6 in the IL-17 pathway."
✎
sparser
"We also find that SUMO2 can competitively block the interaction between the Usp25 UBR and its ubiquitin substrates."
✎
sparser
"Under this assumption, three residues (Phe-4, Thr-12, and Thr-14) in the N-terminal region of Ub, which interact with USP21, are proposed to play key roles in substrate-specific binding."
✎
reach
"Using the ubiquitin and USP21 complex as a model, a contiguous 18-amino acid segment on wild-type human ubiquitin (positions 54 to 71) was selected for the design (XREF_FIG)."
✎
sparser
"SUMOylation at residues Lys99 and Lys141 of the UIM domain can inactivate USP25 and impair the ability of USP25 to hydrolyse the Ub chain by inhibiting the binding of USP25 to Ub chains in vitro ( xref )."
✎
reach
"Ensembles of the ubiquitin and USP21 complex were created (i) from a 100-ns molecular dynamic (MD) simulation by extracting structures every 40 ps and (ii) from structures whose atoms satisfy multiple atomic distance constraints, such as bond distances, after refining structures whose atoms were randomly initialized within an 8-nm 3 cube centered on the input positions as applied by the CONCOORD method."
✎
reach
"Ub dist binds to the S1 site in MINDY1 with a buried surface area of only $750 Å 2 , a binding interface much smaller than those of other DUBs such as HAUSP/USP7 (1,700 Å 2 ), USP21 (1,700 Å 2 ), or USP2 (1,900 Å 2 ), which rely more on Ub dist binding for activity (Hu et al., 2002; Renatus et al., 2006; Ye et al., 2011) ."
✎
reach
"Here we use the ubiquitin and USP21 complex as our model and evaluate the FlexiBaL-GP design method by its ability to identify ubiquitin variants that tightly binds USP21."
✎
sparser
"The catalytic activity and ubiquitin-binding domains of USP25 appear necessary both to rescue ERAD substrates and to lower the levels of HRD1-associated ubiquitinated species, suggesting that USP25 must bind ubiquitin chains in order to cleave them."
✎
sparser
"To clarify whether SUMO2 can competitively block interaction of the Usp25 UBR with ubiquitin substrates, we carried out NMR competition experiments."
✎
reach
"Overexpression of USP21 significantly reduced ubiquitin incorporation into MARK1 but has less impact on the MARK1K768A mutant (XREF_SUPPLEMENTARY)."
✎
reach
"For example, it is associated with endoplasmic reticulum-associated degradation , and acute endoplasmic reticulum (ER) stress regulates amyloid precursor protein processing through ubiquitin-dependent degradation by USP25 ."
✎
reach
"Accordingly, incubation with USP21 abrogated the Ub smearing pattern, leading to the appearance of oligomeric, as well as monomeric forms of MLKL (Fig. 2f)."
✎
reach
"Deletion of one or both UIM domains of USP25 does not alter C-terminal processing activity but strongly impairs K48 and K63 ubiquitin chain cleavage."
✎
reach
"To further identify which Ub linkage type is targeted by USP25 in vivo, HEK-293T cells were transfected with HA-K48-Ub or HA-K63-Ub in lieu of HA-Ub."
✎
reach
"Interestingly, we observed the opposite pattern with USP21, which rescued ubiquitin availability but was unable to rescue degradation of our panel of substrates."
✎
reach
"Additionally USP21 may target not only ubiquitin conjugated substrates but also substrates conjugated to ubiquitin like proteins ISG15 and NEDD8 (Gong et al., 2000; Ye et al., 2011)."
✎
reach
"Reciprocal immunoprecipitation with anti-EZH2 and immunoblotting with EZH2 and USP21 also confirmed that USP21 interacts with EZH2 in vivo (XREF_FIG)."
✎
reach
"XREF_BIBR - XREF_BIBR Subsequently, we verified the interaction between USP21 and EZH2 through co-IP analysis."
✎
reach
"Here, co-IP and GST pull-down analysis demonstrated that USP21 interacted with EZH2."
✎
sparser
"Reciprocal immunoprecipitation with anti-EZH2 and immunoblotting with EZH2 and USP21 also confirmed that USP21 interacts with EZH2 in vivo ( xref )."
✎
sparser
"We found that there were 11 matching peptides from EZH2, which suggested that USP21 was associated with EZH2 in vivo."
✎
sparser
"Here, co-IP and GST pull-down analysis demonstrated that USP21 interacted with EZH2."
✎
sparser
"EZH2 was reported to have a high expression in BC and correlated with EMT. xref – xref Subsequently, we verified the interaction between USP21 and EZH2 through co-IP analysis."
✎
reach
"Furthermore, we identified that USP21 directly regulated the protein level of EZH2 through its DUB activity."
✎
reach
"USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B-cell lymphoma."
✎
reach
"Moreover, the inhibition of USP21 could decrease the expression of EZH2; while adding MG132, the expression of EZH2 was revived."
✎
reach
"Furthermore, we then identify USP21 modulates the protein level of EZH2, a key regulatory gene of DLBCL growth."
✎
reach
"The deubiquitinase USP21 promotes cell proliferation by maintaining the EZH2 protein level in DLBCL."
✎
reach
"As EZH2 has been reported to promote cell metastasis in BC, our work identified that USP21 deubiquitinated EZH2 and stabilized it."
✎
reach
"45 USP21 could suppress EZH2 ubiquitination and thus promotes cell proliferation and metastasis in bladder carcinoma."
✎
reach
"USP21 can deubiquitinate and stabilize EZH2 to induce cell proliferation and metastasis of bladder cancer (150)."
✎
reach
"Chen Y. et al identify that USP21 can deubiquitinate and stabilize EZH2 to promote cell proliferation and metastasis in bladder carcinoma (31); Zhang P. et al find that ZRANB1 is an EZH2 deubiquitinase and regulates EZH2 function in breast cancer through both catalytic activity-dependent and -independent manner (32)."
✎
reach
"We next asked whether USP21 mediated BRCA2 stabilization involves USP21 interaction with the BRCA2 and RAD51 complex."
✎
reach
"USP21 stabilizes BRCA2 in patient derived HCC tumor cell lines, protects from DNA damage and promotes tumor cell growth in a BRCA2 dependent manner."
✎
reach
"We next asked if USP21 mediated BRCA2 fragment stabilization is associated with changes in poly-ubiquitination."
✎
reach
"Our data collectively point to a mechanism of USP21 mediated BRCA2 stabilization via proteasomal degradation."
✎
reach
"To gain mechanistic insight into USP21 function in HCC, we asked whether USP21 can modulate BRCA2 stability in HCC derived tumor cells 50."
✎
reach
"Together, these findings support the notion that USP21 promotes BRCA2 stability and protects from DNA damage accumulation in BRCA2-proficient tumor cells, which can in turn contribute to increased tumor growth and, ultimately, a more malignant phenotype."
✎
reach
"To determine whether USP21 can promote the deubiquitination of endogenous BRCA2 and/or the BRCA2 associated RAD51 and PALB2 proteins XREF_BIBR, XREF_BIBR, we measured the extent of (poly-) ubiquitin modifications on either protein in the presence or absence of USP21 overexpression."
✎
reach
"We now show that USP21 interacts with and deubiquitinates BRCA2 and that USP21 loss results in decreased BRCA2 expression in tumor cell lines."
✎
reach
"USP21 interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51 loading at DNA double-strand breaks."
✎
reach
"USP21 interacts with, and stabilises the BRCA2–RAD51 complex by antagonising degradative BRCA2 ubiquitination."
✎
sparser
"Biochemical dissection suggests that USP21 can associate with the C-terminal OB domains of BRCA2, and consistent with this, a tumor cell line with a C-terminal BRCA2 truncation is unresponsive to USP21 depletion with regard to BRCA2 stability and tumor growth (Figs. xref d and xref )."
✎
reach
"We now show that USP21 interacts with and deubiquitinates BRCA2 and that USP21 loss results in decreased BRCA2 expression in tumor cell lines."
✎
reach
"USP4, for example, interacts directly with end resection factors CtIP and MRN [172], USP21 deubiquitinates and stabilizes BRCA2 to promote RAD51 binding and successful HR [173], and USP10 deubiquitinates and stabilizes p53 to promote its nuclear localization and apoptosis in response to DSBs [174]."
✎
reach
"To determine whether USP21 is sufficient to deubiquitinate BRCA2 fragments, we performed in vitro deubiquitination assays using HA ubiquitinated, immuno purified BRCA2 fragments as well as full-length Flag-BRCA2."
✎
reach
"To determine whether USP21 can promote the deubiquitination of endogenous BRCA2 and/or the BRCA2 associated RAD51 and PALB2 proteins XREF_BIBR, XREF_BIBR, we measured the extent of (poly-) ubiquitin modifications on either protein in the presence or absence of USP21 overexpression."
✎
reach
"USP21 knockdown with two independent shRNAs caused a reduction in BRCA2 protein levels that was particularly pronounced in the presence of the topoisomerase I inhibitor camptothecin (CPT), which causes DSB induction in HR-permissive S phase cells 36."
✎
reach
"Notably, USP21 overexpression caused a significant, DUB activity dependent increase in BRCA2 fragment levels that correlated with the extent of USP21 interaction and was most pronounced for the OB domain containing constructs."
✎
reach
"Consistent with our model, we demonstrate a direct interaction between USP25 and TNKS in adipocytes, both of which cofractionate with a subpopulation of internal GLUT4 containing membranes."
✎
reach
"Binding of both USP25 and IRAP to TNKS in adipocytes could serve to recruit USP25 to GSVs."
✎
sparser
"We show that C44 disrupts the interaction between TNKS and USP25 leading to a higher half-life of AXIN and the breakdown of <beta>-catenin protein."
✎
reach
"The effect of disruption of the interaction between TNKS and USP25 by small molecules on prostate cancer proliferation is unknown."
✎
sparser
"The effect of disruption of the interaction between TNKS and USP25 by small molecules on prostate cancer proliferation is unknown."
✎
reach
"We show that C44 disrupts the interaction between TNKS and USP25 leading to a higher half-life of AXIN and the breakdown of <beta>-catenin protein."
✎
sparser
"The analysis led to the discovery that the small molecule C44 disrupted the interaction between TNKS and USP25, leading to an increase in the half-life of axin, which in turn regulated the Wnt/β-catenin pathway."
✎
sparser
"The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes."
✎
sparser
"In addition, the ubiquitin-specific protease USP25 antagonizes Wnt signaling by promoting deubiquitination and stabilization of PARP5a/b, and disruption of PARP5a interaction with USP25 destabilizes PARP5a/b, leading to Axin1/2 stabilization and subsequent attenuation of Wnt signaling [ xref ]."
✎
sparser
"Here we demonstrate that USP25 and Tankyrase interact, and colocalise with GLUT4 in insulin-sensitive cells."
✎
reach
"We next expressed and purified His USP21, MBP and MBP-FOXP3 from Escherichia coli, and carried out an in vitro MBP pulldown assay that confirmed the direct interaction between FOXP3 and USP21 (XREF_FIG)."
✎
reach
"Reciprocal immunoprecipitation of FLAG-FOXP3 and Myc-USP21 revealed an interaction between USP21 and FOXP3 (XREF_FIG), and we also detected the endogenous interaction between USP21 and FOXP3 in human Treg cells (XREF_FIG)."
✎
sparser
"In Tregs, FOXP3 binds to the promoter region of USP21 and activates its transcription, and USP21 interacts with GATA3 and deubiquitinates it, thus inhibiting its degradation by the proteasome and maintaining its stability."
✎
sparser
"Furthermore, we found that FOXP3 could directly bind to the USP21 gene promoter and activated its transcription upon TcR stimulation."
✎
sparser
"We next expressed and purified His-USP21, MBP and MBP-FOXP3 from Escherichia coli , and carried out an in vitro MBP pulldown assay that confirmed the direct interaction between FOXP3 and USP21 ( xref )."
✎
sparser
"Reciprocal immunoprecipitation of FLAG-FOXP3 and Myc-USP21 revealed an interaction between USP21 and FOXP3 ( xref ), and we also detected the endogenous interaction between USP21 and FOXP3 in human Treg cells ( xref )."
✎
reach
"To test whether USP21 is a direct E3 deubiquitinase of FOXP3 that prevents its degradation, we first carried out binding studies to determine whether FOXP3 could directly bind to USP21."
✎
sparser
"This work proposes that in Tregs, USP21, GATA3, and FOXP3 may form a positive loop to promote FOXP3 expression and thus modulate Treg activity."
✎
sparser
"Thus, USP21, GATA3, and FOXP3 could form a positive loop in promoting FOXP3 expression that in turns modulates Treg cell activity ( xref )."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [ xref ]."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [111]."
✎
reach
"The authors of this study propose that augmentation of USP21 expression by Foxp3 and TCR activation enhances GATA3 levels, which in turn stabilizes Foxp3 function."
✎
reach
"This last report proposed that after TCR stimulation, FOXP3 upregulates USP21 transcription."
✎
reach
"Interestingly, Foxp3 directly activates expression of USP21, and siRNA knockdown of USP21 downregulates both GATA3 and Foxp3 protein."
✎
reach
"Then, USP21 prevents Foxp3 degradation, which further enhances the transcription of Usp21 and suppresses Th1 like phenotypes."
✎
reach
"We have screened 2640 compounds and identified the gut microbial metabolite gallic acid, which promotes Foxp3 degradation and T reg instability by repressing Usp21 gene transcription."
✎
reach
"However, our data suggest that FOXP3 should be an important target of USP21 in Treg cells, since FOXP3 critically controls Treg-cell development and functional stability."
✎
reach
"We observed increased frequency of CD62L lo CD44 hi effector memory T cells in Usp21 fl/fl Foxp3 Cre mice (XREF_FIG)."
✎
reach
"USP25, a ubiquitin C-terminal hydrolase, also binds to Syk in a phosphotyrosine independent manner [XREF_BIBR]."
✎
reach
"As shown in Fig. 4, forced LYN kinase expression did not however alter the USP25 and SYK interaction, further suggesting that the presence of a phosphotyrosine residue is not required for this peculia[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
sparser
"These results demonstrate that USP25 specifically interacts with SYK and suggest that the binding determinants are not conserved in their respective paralogs."
✎
sparser
"Mapping of the interacting domains on USP25 and SYK is summarized in Fig. 3 B.
Our data also demonstrate that the SYK–USP25 interaction occurs in the absence of the kinase domain of SYK."
✎
reach
"These results demonstrate that USP25 specifically interacts with SYK and suggest that the binding determinants are not conserved in their respective paralogs.To determine whether USP25 binds to SYK in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
reach
"Thus, USP25 and tensin2 bind Syk by different mechanisms and do not share a common binding site."
✎
sparser
"Thus, USP25 and tensin2 bind Syk by different mechanisms and do not share a common binding site."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV induced activation of IFN-beta (XREF_FIG), IRF3 (XREF_FIG), NF-kappaB (XREF_FIG) and ISRE (XREF_FIG) in a dose dependent manner."
✎
reach
"Interestingly, the genetic deletion of USP21 in macrophages enhances IRF3 activation, IFN production, and antiviral response."
✎
reach
"We observed that overexpression of USP25 significantly inhibited SEV-induced activation of IRF3 and NF-κB (Figure 3A and B)."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β (Figure 6A), IRF3 (Figure 6B), NF-κB (Figure 6C) and ISRE (Figure 6D) in a dose-dependent manner."
✎
reach
"We observed that overexpression of USP25 significantly inhibited SEV induced activation of IRF3 and NF-kappaB (XREF_FIG)."
✎
reach
"Collectively, these findings suggest that USP25 inhibits RIG-I/MDA5-dependent type I IFN signaling.To better understand the effects of USP25 in SEV-induced type I IFN signaling, we assessed whether expression of USP25 disrupts SEV-induced activation of IRF3 and NF-κB, the two important transcriptional factors in type I IFN signaling."
✎
reach
"USP21 inhibits RIG-I-CARD-mediated IRF3 activation and negatively regulates antiviral response."
✎
reach
"To better understand the effects of USP25 in SEV induced type I IFN signaling, we assessed whether expression of USP25 disrupts SEV induced activation of IRF3 and NF-kappaB, the two important transcriptional factors in type I IFN signaling."
✎
reach
"USP21 inhibits virus induced IRF3 activation via binding to and deubiquitinating RIG-I."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"The results showed that overexpression of USP25 downregulated SEV induced phosphorylation of IRF3 and p65 (XREF_FIG)."
✎
reach
"Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65."
✎
reach
"The results showed that overexpression of USP25 downregulated SEV-induced phosphorylation of IRF3 and p65 (Figure 3C and D)."
✎
reach
"Overexpression of USP25 inhibited virus induced activation of IFN-beta, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-kappaB), as well as the phosphorylation of IRF3 and NF-kappaB subunit p65."
✎
reach
"USP25 also inhibits the activation and phosphorylation of IRF3 and NF-kappaB [XREF_BIBR]."
✎
reach
"Our results show that expression of Usp25 in Usp25 BMDMs largely reverses ACS-induced phosphorylation of TBK1, IRF3, and P65 (Figure 5A)."
✎
sparser
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent
To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I and TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
✎
reach
"Previous study indicated that USP21 can also bind RIG-I to regulate SeV infection."
✎
reach
"Our data showed that USP21 bound to RIG-I via multiple regions, which were different from the binding regions to STING (XREF_FIG)."
✎
sparser
"Usp21 knockout mice showed enhanced antiviral responses to SeV and VSV, but unlike USP3, viral infection was not necessary to facilitate the interaction between RIG-I and USP21."
✎
sparser
"In antiviral responses, USP21 binds to and deubiquitinates RIG-I in the cytoplasm to exert an immunomodulatory effect; USP21 can also hydrolyzes the K27/63-linked polyubiquitin chain on STING to negatively regulate DNA virus-induced type I interferon production [ xref ]."
✎
reach
"Usp21 knockout mice showed enhanced antiviral responses to SeV and VSV, but unlike USP3, viral infection was not necessary to facilitate the interaction between RIG-I and USP21."
✎
reach
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25.In recent years, USP25 has been extensively studied and some novel functions have been revealed."
✎
sparser
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
✎
sparser
"USP25 interacts with RIG-I and TRAF6. (A, B) HEK-293T cells grown in 100-mm dishes were co-transfected with the indicated plasmids encoding the RIG-I (A) or TRAF6 (B) expression vector (4 μg) and HA-USP25WT/ HA-USP25C178A/ HA-USP25H607A (4 μg) using Lipofectamine 2000."
✎
sparser
"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see Figure S1 )."
✎
sparser
"Previous study indicated that USP21 can also bind RIG-I to regulate SeV infection ( xref )."
✎
reach
"CD3delta interacts with both USP25 and HRD1 in cells (XREF_FIG), suggesting a functional interaction between HRD1 and USP25 in ERAD."
✎
sparser
"The interaction between USP25 and HRD1 could serve as an editing step to help determine whether a protein should undergo ERAD."
✎
reach
"In addition, USP25 interacts with the ubiquitin ligase HRD1 and rescues several endoplasmic reticulum associated degradation (ERAD) substrates from degradation by the proteasome [XREF_BIBR]."
✎
reach
"Blount and colleagues showed that exogeneous USP25 interacts with the E3 ligase Hrd1 and with p97 XREF_BIBR."
✎
sparser
"By conducting co-immunoprecipitation experiments from cells, we found that exogenous USP25 interacts with the ER-resident ubiquitin ligase HRD1 and with endogenous VCP/p97 ( xref )."
✎
reach
"By conducting co-immunoprecipitation experiments from cells, we found that exogenous USP25 interacts with the ER-resident ubiquitin ligase HRD1 and with endogenous VCP and p97 (XREF_FIG)."
✎
reach
"Lastly, neither the UBA nor the UIMs of USP25 appear important for its ability to interact with HRD1, since HRD1 interacts with USP25 lacking either domain (XREF_FIG)."
✎
sparser
"Importantly, HRD1 and endogenous USP25 interact in cells ( xref ), but USP25 does not interact with other ubiquitin ligases implicated in ERAD xref , xref – xref : UFD2/E4B ( xref ) and GP78/AMFR ( xref )."
✎
sparser
"CD3δ interacts with both USP25 and HRD1 in cells ( xref ), suggesting a functional interaction between HRD1 and USP25 in ERAD."
✎
reach
"According to our results, USP25 : a) interacted with and rescued the ERAD substrates CD3delta and APP, and counteracted HRD1 effects on CD3delta, b) localized in part at the ER and interacted with the ERAD components HRD1 and VCP and p97, c) reduced the levels of endogenous ubiquitinated species associated with HRD1 and VCP and p97, and d) regulated the levels of endogenous APP, as knockdown of endogenous USP25 was associated with lower levels of endogenous APP."
✎
sparser
"After treatment with the ionophore, USP25 interaction with APP was decreased ( xref )."
✎
sparser
"According to our results, USP25: a) interacted with and rescued the ERAD substrates CD3δ and APP, and counteracted HRD1 effects on CD3δ, b) localized in part at the ER and interacted with the ERAD components HRD1 and VCP/p97, c) reduced the levels of endogenous ubiquitinated species associated with HRD1 and VCP/p97, and d) regulated the levels of endogenous APP, as knockdown of endogenous USP25 was associated with lower levels of endogenous APP."
✎
sparser
"Our observations that USP25 interacted with APP and affected APP turnover implicate USP25 in Alzheimer's Disease pathogenesis and may serve as a point of intervention for new therapeutic strategies."
✎
reach
"After treatment with the ionophore, USP25 interaction with APP was decreased (XREF_FIG)."
✎
reach
"Our observations that USP25 interacted with APP and affected APP turnover implicate USP25 in Alzheimer 's Disease pathogenesis and may serve as a point of intervention for new therapeutic strategies."
✎
reach
"Together, these findings suggest that the activation of A23187 mediated ERAD resulted in APP degradation, and that USP25 inhibits APP degradation by the proteasome."
✎
reach
"Similarly to what occurs with CD3delta, overexpression of USP25 increases APP half-life."
✎
reach
"The positive effect of USP25 on APP protein is detectable only when the proteasome is active; treatment of transfected cells with the inhibitor MG132 abolishes this effect (XREF_FIG), suggesting that USP25 rescues APP from proteasomal degradation."
✎
reach
"We investigated whether USP25 prevents APP degradation under ER-stress conditions."
✎
sparser
"Although USP25 interacted with TRAF3 constitutively in overexpression system in 293T cells, IL-17 treatment did not induce USP25-TRAF3 association in HBECs or MEFs."
✎
sparser
"Therefore, the interaction between USP25 and TRAF3 eliminates K48-linked polyubiquitin chains from TRAF3 and causes ET."
✎
reach
"However, the signals that stimulate an association between USP25 and TRAF3 are unknown."
✎
sparser
"Because USP25 interacted with TRAF3 after stimulation with LPS and because the enzyme activity of USP25 was required for its regulation of TLR4 signaling ( xref and xref ), we hypothesized that USP25 might target TRAF3 for deubiquitination in response to LPS."
✎
reach
"Because USP25 interacted with TRAF3 after stimulation with LPS and because the enzyme activity of USP25 was required for its regulation of TLR4 signaling (XREF_FIG and XREF_FIG), we hypothesized that USP25 might target TRAF3 for deubiquitination in response to LPS."
✎
reach
"We found that stimulation with LPS or Pam 3 CSK 4, but not poly (I : C), promoted an association between USP25 and TRAF3 (XREF_FIG)."
✎
reach
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17."
✎
reach
"Although USP25 interacted with TRAF3 constitutively in overexpression system in 293T cells, IL-17 treatment did not induce USP25-TRAF3 association in HBECs or MEFs."
✎
reach
"[179] USP25 interacts with TRAF3 and TRAF6 following RNA virus or DNA virus infection and prevents TRAF3 and TRAF6 from proteasomal degradation via deubiquitinating K48 linked polyubiquitin chains."
✎
reach
"These data suggest that LPS stimulates the recruitment of USP25 and TRAF3 to the TLR4 signaling complex in which USP25 interacts with TRAF3."
✎
sparser
"Upon infection with an RNA or DNA virus, USP25 associates with TRAF3 and TRAF6 and protects TRAF3 and TRAF6 from virus-induced proteasome-dependent or independent degradation ( xref )."
✎
sparser
"USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
reach
"Therefore, the interaction between USP25 and TRAF3 eliminates K48 linked polyubiquitin chains from TRAF3 and causes ET."
✎
reach
"CD3delta interacts with both USP25 and HRD1 in cells (XREF_FIG), suggesting a functional interaction between HRD1 and USP25 in ERAD."
✎
sparser
"The interaction between USP25 and HRD1 could serve as an editing step to help determine whether a protein should undergo ERAD."
✎
reach
"In addition, USP25 interacts with the ubiquitin ligase HRD1 and rescues several endoplasmic reticulum associated degradation (ERAD) substrates from degradation by the proteasome [XREF_BIBR]."
✎
reach
"Blount and colleagues showed that exogeneous USP25 interacts with the E3 ligase Hrd1 and with p97 XREF_BIBR."
✎
sparser
"By conducting co-immunoprecipitation experiments from cells, we found that exogenous USP25 interacts with the ER-resident ubiquitin ligase HRD1 and with endogenous VCP/p97 ( xref )."
✎
reach
"By conducting co-immunoprecipitation experiments from cells, we found that exogenous USP25 interacts with the ER-resident ubiquitin ligase HRD1 and with endogenous VCP and p97 (XREF_FIG)."
✎
reach
"Lastly, neither the UBA nor the UIMs of USP25 appear important for its ability to interact with HRD1, since HRD1 interacts with USP25 lacking either domain (XREF_FIG)."
✎
sparser
"Importantly, HRD1 and endogenous USP25 interact in cells ( xref ), but USP25 does not interact with other ubiquitin ligases implicated in ERAD xref , xref – xref : UFD2/E4B ( xref ) and GP78/AMFR ( xref )."
✎
sparser
"CD3δ interacts with both USP25 and HRD1 in cells ( xref ), suggesting a functional interaction between HRD1 and USP25 in ERAD."
✎
reach
"A series of in vitro experiments testified that USP21 regulated the expression of MAPK1 by binding to transcription factor GATA3, thereby regulating the tumor growth and cell stemness of GC."
✎
sparser
"In agreement with this previous study, we confirmed the endogenous interaction between USP21 and GATA3 in human expanding Treg cells ( xref )."
✎
reach
"In agreement with this previous study, we confirmed the endogenous interaction between USP21 and GATA3 in human expanding Treg cells (XREF_SUPPLEMENTARY)."
✎
reach
"Here, we show how USP21 interacts with and stabilizes GATA3 by mediating its deubiquitination."
✎
reach
"In order to further explore possible functional interactions between USP21 and GATA3, we carried out an in depth characterization of hematopoiesis and lymphocyte differentiation in the Usp21 -/- mice."
✎
sparser
"In Tregs, FOXP3 binds to the promoter region of USP21 and activates its transcription, and USP21 interacts with GATA3 and deubiquitinates it, thus inhibiting its degradation by the proteasome and maintaining its stability."
✎
reach
"Zhang et al. have reported that in Treg cells, the DUB USP21 interacted with and stabilized GATA3 via deubiquitination with the overexpression of USP21 obviously decreasing the ubiquitination status of GATA3."
✎
sparser
"This work proposes that in Tregs, USP21, GATA3, and FOXP3 may form a positive loop to promote FOXP3 expression and thus modulate Treg activity."
✎
sparser
"Thus, USP21, GATA3, and FOXP3 could form a positive loop in promoting FOXP3 expression that in turns modulates Treg cell activity ( xref )."
✎
reach
"Ubv.21.4 CDelta2 coimmunoprecipitated with USP21 in cotrans fected human embryonic kidney (HEK) 293T cells (XREF_FIG), blocked the deubiquitination of RIP1 by USP21 (XREF_FIG), and restored NF-kappaB activation (XREF_FIG)."
✎
reach
"For example, Junichiro et al. demonstrated that USP21 constitutively deubiquitinates RIP1 in vitro and in vivo [40]; and a previous study has reported that USP20 deubiquitinates TRAF6 and Tax in vivo [40]."
✎
reach
"USP21 is constitutively associated with RIP1 and deubiquitinates RIP1 in vitro and in vivo."
✎
reach
"A previous study showed that USP21 deubiquitylates receptor interacting protein 1, a suppressor of TNF induced NF-KB activation."
✎
reach
"Ubv.21.4 blocked the deubiquitination of RIP1 by USP21 and restored NF-jB activation, showing that it acts as an inhibitor of USP21 in cells."
✎
reach
"Ubv.21.4 blocked the deubiquitination of RIP1 by USP21 and restored NF‐κB activation, showing that it acts as an inhibitor of USP21 in cells."
✎
reach
"Ubv.21.4 blocked the deubiquitination of RIP1 by USP21 and restored NF‐κB activation, showing that it acts as an inhibitor of USP21 in cells."
✎
sparser
"USP21 interacts with RIP1 and deubiquitinates RIP1 in a DUB-dependent manner ( xref )."
✎
sparser
"To explore the possible functional interactions between USP21 and RIPK1 in these pathways, we derived macrophages and dendritic cells from the bone marrow of Usp21 -/- and wild types age-matched control mice, and compared their responses to TLR3, TLR4 and TNFR stimulation."
✎
reach
"To explore the possible functional interactions between USP21 and RIPK1 in these pathways, we derived macrophages and dendritic cells from the bone marrow of Usp21 -/- and wild types age matched control mice, and compared their responses to TLR3, TLR4 and TNFR stimulation."
✎
sparser
"USP21 is constitutively associated with RIP1 and deubiquitinates RIP1 in vitro and in vivo."
✎
reach
"By contrast, USP21 inhibits TNF-alpha-induced NF-kappaB signaling by promoting the deubiquitination of receptor interacting protein 1 (RIP1) in HeLa cells."
✎
reach
"Ubiquitinated receptor-interacting protein 1 (RIP1) is a positive regulator of NF-jB activation induced by TNF-a, and in turn, USP21 has been shown to down-regulate TNF-a-induced NF-jB activation by deubiquitinating RIP1 [138] ."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV induced activation of IFN-beta (XREF_FIG), IRF3 (XREF_FIG), NF-kappaB (XREF_FIG) and ISRE (XREF_FIG) in a dose dependent manner."
✎
reach
"The deubiquitinases (DUBs) A20 and USP25 negatively regulate IL-17-induced NF-kappaB and MAPK activation by removing ubiquitin modifications on TRAF6."
✎
reach
"USP21 was reported to target RIPK1 and inhibit NF-kappaB activity 96, however mice lacking USP21 show no defect in NF-kappaB signalling 93."
✎
reach
"Interestingly, we found that overexpression of USP21 WT but not C221A mutant inhibited IFN-beta, NF-kappaB, and ISRE reporter activities in HEK293T cells in response to transfected poly (I : C), which was known to be mediated by MDA5 (unpublished data), suggesting that USP21 might also target MDA5."
✎
reach
"We observed that overexpression of USP25 significantly inhibited SEV induced activation of IRF3 and NF-kappaB (XREF_FIG)."
✎
reach
"To better understand the effects of USP25 in SEV induced type I IFN signaling, we assessed whether expression of USP25 disrupts SEV induced activation of IRF3 and NF-kappaB, the two important transcriptional factors in type I IFN signaling."
✎
reach
"USP21 inhibits NF-kB activation through the deubiquitylation of RIPK1 [XREF_BIBR]."
✎
reach
"Because USP25 negatively regulates IL-17-induced activation of NF-kappaB and stabilization of chemokine mRNA, which involves TRAF6 and TRAF5, respectively 26, we examined whether USP25 interacts with these TRAF proteins."
✎
reach
"The analysis suggested that reconstitution of USP25 almost completely inhibited IL-17-induced activation of NF-kappaB compared to USP25 (C178S) (0.89 v.s 1.8 at 15 min, 0.61 v.s. 8.3 at 30 min, respectively) (XREF_FIG)."
✎
reach
"Because IFN-beta reporter activity is dependent on both NF-kappaB and IRF3, we further tested the inhibitory effect of USP21 on SeV-, RIG-I-CARD-, and TBK1 induced NF-kappaB and ISRE reporter activities."
✎
reach
"Overexpression studies in HEK293T cells revealed that USP21 might also bind and deubiquitinate MDA5 by removing K63 linked polyubiquitination, thus inhibiting IFN-beta, NF-kappaB, and IFN stimulated response element (ISRE) reporter activities."
✎
reach
"An additional study has revealed that depletion of USP21 decreases IL33 protein levels and IL33 mediated NF-kappaB p65 promoter activity, indicating USP21 is able to positively regulate the NF-kappaB signaling pathway."
✎
sparser
"We found that the DUB, USP25 xref inhibited IL-17-but not TNF-induced activation of NF-κB in reporter assays in HeLa cells and in 293T cells transfected with IL-17RA and IL-17RC (293T-IL-17RA/C) ( xref and xref )."
✎
sparser
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent
To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
sparser
"The analysis suggested that reconstitution of USP25 almost completely inhibited IL-17-induced activation of NF-κB compared to USP25(C178S) (0.89 v."
✎
sparser
"We now show that USP21 interacts with MEK2, and regulates the Lys48-linked polyubiquitination of MEK2."
✎
reach
"While in hepatocellular carcinoma, USP21 binds to MEK2 and regulates the polyubiquitination at Lys48, thereby stabilizing MEK2 and up-regulating ERK1/2 to support sustained proliferation and oncogenic signals."
✎
sparser
"In the former case, we used either wild-type USP21 or a C221A mutation which has been shown to lack de-ubiquitinase activity We confirmed that USP21 and MEK2 could interact reciprocally and in a manner that is independent of its DUB activity (Fig. xref )."
✎
sparser
"Our findings provide a better understanding of HCC progression and identify a novel strategy for the clinical treatment for HCC by targeting the USP21-MEK2 interaction and its functional consequences."
✎
sparser
"While in hepatocellular carcinoma, USP21 binds to MEK2 and regulates the polyubiquitination at Lys48, thereby stabilizing MEK2 and up-regulating ERK1/2 to support sustained proliferation and oncogenic signals ( xref )."
✎
reach
"Mechanistically, USP21 physically associates with MEK2 and stabilizes MEK2 by deubiquitination, thereby contributing to the activation of the MEK2 substrate ERK1/2."
✎
sparser
"To validate this funding, co-immunoprecipitation assays were used to detect the interaction between ectopically expressed Flag-tagged USP21 and HA-tagged MEK2."
✎
sparser
"Mechanistically, USP21 physically associates with MEK2 and stabilizes MEK2 by deubiquitination, thereby contributing to the activation of the MEK2 substrate ERK1/2."
✎
reach
"We now show that USP21 interacts with MEK2, and regulates the Lys48 linked polyubiquitination of MEK2."
✎
sparser
"Using antibodies to various TRAF for immunoprecipitation revealed that USP25 interacted with TRAF5 and TRAF6, but not with TRAF3 in HBECs or MEFs after IL-17 stimulation, while TNF stimulation induced neither USP25-TRAF5, USP25-TRAF6 nor USP25-TRAF3 association ( xref and data not shown)."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"USP25 interacts with TRAF5 and TRAF6 and deubiquitinates Act1-mediated K63-linked ubiquitination of TRAF5 and TRAF6, thereby turning off IL-17 signaling."
✎
sparser
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6 and USP25 induced removal of Act1-mediated K63-linked ubiquitination in TRAF5 and TRAF6."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6, and the USP25 deubiquitination activity opposed the activity of the Act1 E3 ubiquitin ligase, which ubiquitinates Lys63 in both TRAF5 and TRAF6."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"Furthermore, we found that TRAF-USP25 interaction depended on Act1, as Act1 deficiency impaired their association ( xref ), indicating that Act1 was required for USP25 to engage TRAF5 and TRAF6 in the IL-17 pathway."
✎
reach
"USP25 also deubiquitinated TRAF5 and TRAF6 to regulate in IL-17 signaling [XREF_BIBR]."
✎
reach
"Therefore, USP25 may indirectly lead to deubiquitination of TRAF5 or TRAF6 through its tightly associated proteins."
✎
reach
"We found that Act1 mediated K63 linked ubiquitination of TRAF5 (XREF_SUPPLEMENTARY), which was substantially attenuated by USP25 but not USP25 (C178S) in 293T cells or in an in vitro deubiquitination system (XREF_FIG and XREF_SUPPLEMENTARY)."
✎
reach
"Taken together, our results demonstrate that USP25 negatively regulates IL-17-triggered ubiquitination of TRAF6 and TRAF5."
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1."
✎
reach
"Similarly, Usp25 deubiquitinates both TRAF5 and TRAF6 and thereby restricts downstream gene expression."
✎
sparser
"USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation in stem-cell like property of human renal cell carcinoma [ xref ]."
✎
sparser
"Mechanistically, USP21 can bind to the promoter of IL-8 gene and modify the histone status for transcriptional initiation."
✎
sparser
"Furthermore, decrease USP21 levels is associated with repression of interleukin 8 (IL-8), a chemokine that regulates CSCs characteristics in RCC."
✎
sparser
"However, whether IL-8 expression level is associated with USP21 and CSCs property in RCC cells remains undefined."
✎
sparser
"As expected, decreased binding of USP21 to the promoter regions of IL-8 was associated with increased uH2A level and decrease of H3K4me3 levels (Figure xref and xref ), confirming the function of USP21 in regulating the transcriptional activities of IL-8 ."
✎
sparser
"Mechanistically, USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation."
✎
sparser
"In current study, we showed that USP21 binds to the promoter region of IL-8 gene and regulates its transcriptional activity."
✎
sparser
"Our results showed that USP21 was detected on the promoters of IL-8 and USP21 knockdown significantly reduced the binding of USP21 to the promoter of IL-8 in 786-O cells (Figure xref )."
✎
sparser
"A study showed that USP21 binds to the promoter of interleukin-8 (IL-8) to transcriptionally mediate its initiation xref ."
✎
reach
"On the other hand, USP21 also mediates transcriptional initiation of IL8 leading to an expansion of the stem cell pool in renal carcinoma cells 13."
✎
reach
"Our results showed that knockdown of USP21 led to decrease of IL-8 secretion in RCC cell lines."
✎
reach
"Our study demonstrates that IL-8 affects the CSCs activity in RCC and how IL-8 activity is mediated by USP21 through its binding to the promoter region."
✎
reach
"USP21 also mediates transcriptional initiation of IL-8 by binding to its promoter 13."
✎
sparser
"Furthermore, Mohideen et al. elucidated the existence of an interaction between USP25 and SUMO2/3 proteins ( xref )."
✎
reach
"Taken together, our results demonstrate that the non covalent binding of SUMO2 to the Usp25 SIM impairs the catalytic activity of the enzyme.SUMO has a global fold similar to that of ubiquitin."
✎
reach
"To understand how Usp25 recognizes SUMO molecules, we investigated the non covalent interaction between Usp25 1-146 and SUMO2."
✎
reach
"Our data strongly suggest that the non covalent binding of SUMO2 to the Usp25 UBR prevents its interaction with ubiquitin substrates."
✎
reach
"Using these antibodies, we also observed that endogenous USP25 interacts more efficiently with SUMO3."
✎
reach
"On the other hand, SUMO2 non covalently binds to the Usp25 UBR and impairs the enzymatic activity of Usp25 by competitively blocking its interaction with ubiquitin substrates."
✎
reach
"Taken together, these findings demonstrate that the interaction between USP25 and SUMO3 involves the SUMO-SIM interface.Since several known SUMO targets can interact noncovalently with SUMO (Boddy et [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
sparser
"To verify that USP25 indeed interacts noncovalently with SUMO2/3, we transiently transfected HA-USP25 into HeLa cells and incubated the lysates with immobilized SUMO1, SUMO3, or control beads."
✎
reach
"While USP25 binds both to SUMO1 and SUMO2/3, it is more efficient with the latter."
✎
sparser
"Whereas we cannot exclude that some aspects of exogenous Gli1-activation rely on primary cilium formation, taken together, our data showing (1) an interaction between USP21 and Gli1, (2) the regulation of PKA-dependent phosphorylation of Gli1 by USP21, and (3) the colocalisation of all three proteins at the centrosome in U2OS cells make a strong case for a regulatory role of USP21 that could be independent of cilium formation."
✎
sparser
"Strikingly, the decrease of Gli1 phosphorylation was concomitant with a decrease in its protein levels, suggesting that USP21-induced phosphorylation of Gli1 is coupled with its stabilisation ( xref C)."
✎
reach
"In particular, Gli transcriptional activity is regulated by several kinases, thus we assessed whether USP21 induces Gli1 phosphorylation."
✎
sparser
"In particular, Gli transcriptional activity is regulated by several kinases, thus we assessed whether USP21 induces Gli1 phosphorylation."
✎
reach
"USP21 is able to interact with GLI1, thereby suppressing GLI1 dependent transcription."
✎
reach
"Likewise, overexpression of GFP-USP21 inhibited Gli1 transcriptional activity to a similar degree, and this inhibition depended on its catalytic activity (XREF_FIG C)."
✎
reach
"In this assay, siRNA mediated depletion of USP21 decreased Gli1 transcriptional activity by ~ 40% (XREF_FIG B)."
✎
sparser
"USP21 is able to interact with GLI1, thereby suppressing GLI1-dependent transcription."
✎
sparser
"Whereas we cannot exclude that some aspects of exogenous Gli1-activation rely on primary cilium formation, taken together, our data showing (1) an interaction between USP21 and Gli1, (2) the regulation of PKA-dependent phosphorylation of Gli1 by USP21, and (3) the colocalisation of all three proteins at the centrosome in U2OS cells make a strong case for a regulatory role of USP21 that could be independent of cilium formation."
✎
reach
"In the late stage of herpes simplex virus 1 (HSV-1) infection, protein kinase p38 phosphorylates USP21 and recruits it to bind to STING."
✎
sparser
"In the late stage of herpes simplex virus 1 (HSV-1) infection, protein kinase p38 phosphorylates USP21 and recruits it to bind to STING."
✎
reach
"Taken together, our results demonstrate that PCV2 infection activates the p38-MAPK signaling pathway mediated USP21 phosphorylation to inhibit the K63 ubiquitination of STING, which prevents the phosphorylation and transportation to the nucleus of IRF3, leading to an increase risk for PPV infection."
✎
reach
"Taken together, these data indicate that p38 mediated USP21 phosphorylation enhances the binding of USP21 to STING."
✎
sparser
"Indeed, it was shown that activated p38 phosphorylates USP21, stimulating deubiquitination of STING leading to in STING inhibition xref ."
✎
reach
"Our data showed that phosphorylation of USP21 by p38 promotes its binding to STING and inactivates STING in response to HSV-1 infection."
✎
sparser
"Importantly, GST pull-down assay showed that phosphorylation of USP21 by activated p38 significantly enhanced the binding of USP21 to the purified STING ( xref )."
✎
reach
"The purified USP21 could be phosphorylated by purified active p38 using in vitro kinase assay (XREF_FIG), suggesting that p38 is a direct kinase that phosphorylates USP21."
✎
sparser
"The purified USP21 could be phosphorylated by purified active p38 using in vitro kinase assay ( xref ), suggesting that p38 is a direct kinase that phosphorylates USP21."
✎
reach
"Importantly, GST pull-down assay showed that phosphorylation of USP21 by activated p38 significantly enhanced the binding of USP21 to the purified STING (XREF_FIG)."
✎
sparser
"We also find that SUMO2 can competitively block the interaction between the Usp25 UBR and its ubiquitin substrates."
✎
sparser
"Under this assumption, three residues (Phe-4, Thr-12, and Thr-14) in the N-terminal region of Ub, which interact with USP21, are proposed to play key roles in substrate-specific binding."
✎
reach
"Using the ubiquitin and USP21 complex as a model, a contiguous 18-amino acid segment on wild-type human ubiquitin (positions 54 to 71) was selected for the design (XREF_FIG)."
✎
sparser
"SUMOylation at residues Lys99 and Lys141 of the UIM domain can inactivate USP25 and impair the ability of USP25 to hydrolyse the Ub chain by inhibiting the binding of USP25 to Ub chains in vitro ( xref )."
✎
reach
"Ensembles of the ubiquitin and USP21 complex were created (i) from a 100-ns molecular dynamic (MD) simulation by extracting structures every 40 ps and (ii) from structures whose atoms satisfy multiple atomic distance constraints, such as bond distances, after refining structures whose atoms were randomly initialized within an 8-nm 3 cube centered on the input positions as applied by the CONCOORD method."
✎
reach
"Ub dist binds to the S1 site in MINDY1 with a buried surface area of only $750 Å 2 , a binding interface much smaller than those of other DUBs such as HAUSP/USP7 (1,700 Å 2 ), USP21 (1,700 Å 2 ), or USP2 (1,900 Å 2 ), which rely more on Ub dist binding for activity (Hu et al., 2002; Renatus et al., 2006; Ye et al., 2011) ."
✎
reach
"Here we use the ubiquitin and USP21 complex as our model and evaluate the FlexiBaL-GP design method by its ability to identify ubiquitin variants that tightly binds USP21."
✎
sparser
"The catalytic activity and ubiquitin-binding domains of USP25 appear necessary both to rescue ERAD substrates and to lower the levels of HRD1-associated ubiquitinated species, suggesting that USP25 must bind ubiquitin chains in order to cleave them."
✎
sparser
"To clarify whether SUMO2 can competitively block interaction of the Usp25 UBR with ubiquitin substrates, we carried out NMR competition experiments."
✎
sparser
"Furthermore, Mohideen et al. elucidated the existence of an interaction between USP25 and SUMO2/3 proteins ( xref )."
✎
reach
"Taken together, our results demonstrate that the non covalent binding of SUMO2 to the Usp25 SIM impairs the catalytic activity of the enzyme.SUMO has a global fold similar to that of ubiquitin."
✎
reach
"To understand how Usp25 recognizes SUMO molecules, we investigated the non covalent interaction between Usp25 1-146 and SUMO2."
✎
reach
"Our data strongly suggest that the non covalent binding of SUMO2 to the Usp25 UBR prevents its interaction with ubiquitin substrates."
✎
reach
"Using these antibodies, we also observed that endogenous USP25 interacts more efficiently with SUMO3."
✎
reach
"On the other hand, SUMO2 non covalently binds to the Usp25 UBR and impairs the enzymatic activity of Usp25 by competitively blocking its interaction with ubiquitin substrates."
✎
reach
"Taken together, these findings demonstrate that the interaction between USP25 and SUMO3 involves the SUMO-SIM interface.Since several known SUMO targets can interact noncovalently with SUMO (Boddy et [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
sparser
"To verify that USP25 indeed interacts noncovalently with SUMO2/3, we transiently transfected HA-USP25 into HeLa cells and incubated the lysates with immobilized SUMO1, SUMO3, or control beads."
✎
reach
"While USP25 binds both to SUMO1 and SUMO2/3, it is more efficient with the latter."
✎
sparser
"Results from IP directed against both Myc-FOXM1b ( xref ) and FLAG-HA-USP21 ( xref ) demonstrate that USP21 binds to a region encompassing FOXM1 amino acids 321–400."
✎
reach
"An interaction between FOXM1 and USP21 was detected by coimmunoprecipitation (co-IP), regardless of whether the immuno precipitation (IP) was directed against Myc-USP21 (XREF_FIG) or HA-FOXM1b (XREF_FIG)."
✎
reach
"reveal that USP21 directly binds to FOXM1, makes it deubiquitinate, and increases its expression level in vitro and in vivo."
✎
reach
"Because USP21 can directly bind and deubiquitinate FOXM1, we next evaluated the impact of USP21 on FOXM1 stability."
✎
reach
"USP21 increases the stability of FOXM1, and USP21 binds and deubiquitinates FOXM1 in vivo and in vitro, indicating a direct enzyme-substrate relationship."
✎
sparser
"Because USP21 can directly bind and deubiquitinate FOXM1, we next evaluated the impact of USP21 on FOXM1 stability."
✎
sparser
"In addition, an interaction between endogenous FOXM1 and USP21 was detected using antibodies directed against USP21 ( xref )."
✎
reach
"In addition, an interaction between endogenous FOXM1 and USP21 was detected using antibodies directed against USP21 (XREF_FIG)."
✎
sparser
"Arceci et al. reveal that USP21 directly binds to FOXM1, makes it deubiquitinate, and increases its expression level in vitro and in vivo ."
✎
reach
"Hence, SNHG16 competitively bound to miR-4500 to regulate the expression of USP21.In the current study, we showed that oncogenic USP21 deubiquitinates and stabilizes YY1 and that YY1 transcriptionally activates lncRNA SNHG16, which further acts as a ceRNA to regulate USP21 (Fig. 8)."
✎
reach
"However, the function of these networks and their mechanisms upstream and downstream in association with the pathogenesis of NSCLC remain poorly understood.Our current study, for the first time, reported that USP21 acted as an oncogene by deubiquitinating YY1 to stabilize its protein levels in NSCLC cells."
✎
reach
"Because USP21 is a DUB, we examined whether USP21 could directly interact with and deubiquitinate YY1."
✎
reach
"The high-molecular-weight conjugates observed were then purified and subjected to blotting for YY1, and the blots demonstrated that wt USP21 but not USP21 C221A reduced YY1 ubiquitination (Fig. 5g)."
✎
reach
"The results showed that USP21 silencing decreased the stability of YY1 and increased its degradation (Fig. 5d)."
✎
reach
"In addition, USP21 overexpression significantly increased SNHG16 expression, whereas silencing of USP21 significantly decreased the expression of SNHG16 (Fig. 6b) as well as YY1."
✎
sparser
"KCTD6 interacts preferentially with catalytically inactive USP21-C221S (USP21CS), which in turn isolates higher-molecular-mass species of mono- and di-ubiquitylated KCTD6 ( xref B,C)."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
reach
"USP21 interacts with KCTD6, a CUL3 substrate adapter, through its catalytic domain."
✎
sparser
"USP21 interacts with KCTD6, a CUL3 substrate adapter, through its catalytic domain."
✎
sparser
"This suggests that the direct interaction of KCTD6 with the USP21 catalytic domain disrupts its regulation of Gli1."
✎
sparser
"This might account for the observed association of USP21 with a C-terminally truncated KCTD6 (residues 114–187) in our Y2H screen."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
sparser
"We asked whether USP21 interacts with a fully assembled KCTD6–CUL3 ligase complex."
E3_Ub_ligase binds USP25, KCTD6, and CUL3. 1 / 1
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1
✎
sparser
"Having shown above that the catalytic domain of USP21 also interacts with the KCTD6–CUL3 E3-ligase complex, we wondered whether KCTD6 would be able to influence Gli1 stability in this setting."
✎
sparser
"We now show that USP21 interacts with MEK2, and regulates the Lys48-linked polyubiquitination of MEK2."
✎
reach
"While in hepatocellular carcinoma, USP21 binds to MEK2 and regulates the polyubiquitination at Lys48, thereby stabilizing MEK2 and up-regulating ERK1/2 to support sustained proliferation and oncogenic signals."
✎
sparser
"In the former case, we used either wild-type USP21 or a C221A mutation which has been shown to lack de-ubiquitinase activity We confirmed that USP21 and MEK2 could interact reciprocally and in a manner that is independent of its DUB activity (Fig. xref )."
✎
sparser
"Our findings provide a better understanding of HCC progression and identify a novel strategy for the clinical treatment for HCC by targeting the USP21-MEK2 interaction and its functional consequences."
✎
sparser
"While in hepatocellular carcinoma, USP21 binds to MEK2 and regulates the polyubiquitination at Lys48, thereby stabilizing MEK2 and up-regulating ERK1/2 to support sustained proliferation and oncogenic signals ( xref )."
✎
reach
"Mechanistically, USP21 physically associates with MEK2 and stabilizes MEK2 by deubiquitination, thereby contributing to the activation of the MEK2 substrate ERK1/2."
✎
sparser
"To validate this funding, co-immunoprecipitation assays were used to detect the interaction between ectopically expressed Flag-tagged USP21 and HA-tagged MEK2."
✎
sparser
"Mechanistically, USP21 physically associates with MEK2 and stabilizes MEK2 by deubiquitination, thereby contributing to the activation of the MEK2 substrate ERK1/2."
✎
reach
"We now show that USP21 interacts with MEK2, and regulates the Lys48 linked polyubiquitination of MEK2."
✎
reach
"Reciprocal immunoprecipitation with anti-EZH2 and immunoblotting with EZH2 and USP21 also confirmed that USP21 interacts with EZH2 in vivo (XREF_FIG)."
✎
reach
"XREF_BIBR - XREF_BIBR Subsequently, we verified the interaction between USP21 and EZH2 through co-IP analysis."
✎
reach
"Here, co-IP and GST pull-down analysis demonstrated that USP21 interacted with EZH2."
✎
sparser
"Reciprocal immunoprecipitation with anti-EZH2 and immunoblotting with EZH2 and USP21 also confirmed that USP21 interacts with EZH2 in vivo ( xref )."
✎
sparser
"We found that there were 11 matching peptides from EZH2, which suggested that USP21 was associated with EZH2 in vivo."
✎
sparser
"Here, co-IP and GST pull-down analysis demonstrated that USP21 interacted with EZH2."
✎
sparser
"EZH2 was reported to have a high expression in BC and correlated with EMT. xref – xref Subsequently, we verified the interaction between USP21 and EZH2 through co-IP analysis."
✎
reach
"According to our results, USP25 : a) interacted with and rescued the ERAD substrates CD3delta and APP, and counteracted HRD1 effects on CD3delta, b) localized in part at the ER and interacted with the ERAD components HRD1 and VCP and p97, c) reduced the levels of endogenous ubiquitinated species associated with HRD1 and VCP and p97, and d) regulated the levels of endogenous APP, as knockdown of endogenous USP25 was associated with lower levels of endogenous APP."
✎
sparser
"After treatment with the ionophore, USP25 interaction with APP was decreased ( xref )."
✎
sparser
"According to our results, USP25: a) interacted with and rescued the ERAD substrates CD3δ and APP, and counteracted HRD1 effects on CD3δ, b) localized in part at the ER and interacted with the ERAD components HRD1 and VCP/p97, c) reduced the levels of endogenous ubiquitinated species associated with HRD1 and VCP/p97, and d) regulated the levels of endogenous APP, as knockdown of endogenous USP25 was associated with lower levels of endogenous APP."
✎
sparser
"Our observations that USP25 interacted with APP and affected APP turnover implicate USP25 in Alzheimer's Disease pathogenesis and may serve as a point of intervention for new therapeutic strategies."
✎
reach
"After treatment with the ionophore, USP25 interaction with APP was decreased (XREF_FIG)."
✎
reach
"Our observations that USP25 interacted with APP and affected APP turnover implicate USP25 in Alzheimer 's Disease pathogenesis and may serve as a point of intervention for new therapeutic strategies."
✎
sparser
"KCTD6 interacts preferentially with catalytically inactive USP21-C221S (USP21CS), which in turn isolates higher-molecular-mass species of mono- and di-ubiquitylated KCTD6 ( xref B,C)."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
reach
"USP21 interacts with KCTD6, a CUL3 substrate adapter, through its catalytic domain."
✎
sparser
"USP21 interacts with KCTD6, a CUL3 substrate adapter, through its catalytic domain."
✎
sparser
"This suggests that the direct interaction of KCTD6 with the USP21 catalytic domain disrupts its regulation of Gli1."
✎
sparser
"This might account for the observed association of USP21 with a C-terminally truncated KCTD6 (residues 114–187) in our Y2H screen."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
sparser
"We asked whether USP21 interacts with a fully assembled KCTD6–CUL3 ligase complex."
E3_Ub_ligase binds USP25, KCTD6, and CUL3. 1 / 1
|
1
✎
sparser
"Having shown above that the catalytic domain of USP21 also interacts with the KCTD6–CUL3 E3-ligase complex, we wondered whether KCTD6 would be able to influence Gli1 stability in this setting."
✎
sparser
"USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation in stem-cell like property of human renal cell carcinoma [ xref ]."
✎
sparser
"Mechanistically, USP21 can bind to the promoter of IL-8 gene and modify the histone status for transcriptional initiation."
✎
sparser
"Furthermore, decrease USP21 levels is associated with repression of interleukin 8 (IL-8), a chemokine that regulates CSCs characteristics in RCC."
✎
sparser
"However, whether IL-8 expression level is associated with USP21 and CSCs property in RCC cells remains undefined."
✎
sparser
"As expected, decreased binding of USP21 to the promoter regions of IL-8 was associated with increased uH2A level and decrease of H3K4me3 levels (Figure xref and xref ), confirming the function of USP21 in regulating the transcriptional activities of IL-8 ."
✎
sparser
"Mechanistically, USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation."
✎
sparser
"In current study, we showed that USP21 binds to the promoter region of IL-8 gene and regulates its transcriptional activity."
✎
sparser
"Our results showed that USP21 was detected on the promoters of IL-8 and USP21 knockdown significantly reduced the binding of USP21 to the promoter of IL-8 in 786-O cells (Figure xref )."
✎
sparser
"A study showed that USP21 binds to the promoter of interleukin-8 (IL-8) to transcriptionally mediate its initiation xref ."
USP25 affects cell growth
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9
USP25 activates cell growth.
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7
USP25 activates cell growth. 7 / 7
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7
✎
reach
"Overexpression of USP21 increase the cell growth, invasion and cancer stem cell percentage of 786-O and A-704 cells."
✎
reach
"We identify that knockdown of USP21 inhibits cell proliferation, and overexpression of USP21 promotes cell growth."
✎
reach
"Amplification of USP21 deubiquitinase promotes pancreatic cancer cell growth and stemness via Wnt and beta-catenin signaling [XREF_BIBR]."
✎
reach
"USP21 deubiquitinates and stabilizes BRCA2, promotes HR efficiency, and enhances homologous recombination efficiency and tumor cell growth."
✎
reach
"USP21 stabilizes BRCA2 in patient derived HCC tumor cell lines, protects from DNA damage and promotes tumor cell growth in a BRCA2 dependent manner."
✎
reach
"Thus far, a study proved that USP21 can accelerate cell growth, invasion, and stemness of renal cell carcinoma."
✎
reach
"Here, we have shown that USP21 over-expression promotes HCC cell growth, cell cycle progression and in vivo tumorigenesis, while knockdown of USP21 inhibits these processes."
USP25 inhibits cell growth.
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2
USP25 inhibits cell growth. 2 / 2
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2
✎
sparser
"However, we repeated this experiment with a larger dose escalation of myc-ZNF598 relative to myc-USP21 and did not observe a consistent decrease in exogenous USP21 expression as ZNF598 expression increased ( xref )."
✎
sparser
"Expression vectors containing Flag-tagged GATA3 (Flag-GATA3) and Myc-tagged USP21 (Myc-USP21) were co-transfected into HEK 293T cells."
✎
sparser
"Flag-GSC was pulled down together with Myc-USP21 ( xref ), indicating that that the two proteins interact."
✎
sparser
"Co-immunoprecipitation assays showed the interaction between the cMyc- and GFP-tagged USP25 proteins, indicating that USP25 formed homodimeric or oligomeric complexes in vivo ( xref )."
✎
sparser
"As detailed in xref , quantification of the exogenous USP21 and ZNF598 protein levels in manuscript Figure 3—figure supplement 2C revealed a decrease in myc-USP21 levels at the highest level of myc-ZNF598 plasmid expression ( xref )."
✎
sparser
"Myc-USP21 was immunoprecipitated with anti-Myc antibody and GATA3 was immunoprecipitated with anti-Flag antibody, and it was found that USP21 and Flag-GATA3 were co-immunoprecipitated ( xref )."
✎
sparser
"This was abrogated upon addition of Myc-USP21, indicating that USP21 is a DUB of GSC."
✎
sparser
"To determine whether USP21 interacts with GSC, HEK 293T cells were co-transfected with expression vectors encoding Flag epitope-tagged GSC (Flag-GSC) and Myc-tagged USP21 (Myc-USP21), followed by reciprocal co-IP."
✎
sparser
"To determine whether USP21 is a DUB of GSC, HEK 293T cells were co-transfected with Flag-GSC and HA-ubiquitin-K0 (HA-Ub-K0), with or without Myc-USP21 and Myc-WWP2; after 2 days, immunoprecipitation was performed using an anti-Flag antibody, and immunoblotting was performed with anti-HA and anti-Flag antibodies."
✎
reach
"Indeed, overexpression of USP21 WT but not C221A mutant inhibited Lys63 linked polyubiquitination of MDA5 and MDA5 mediated IFN-beta, NF-kappaB, and ISRE reporter activities (unpublished data) and USP21 could also bind to MDA5 and LGP2 (unpublished data)."
✎
reach
"Furthermore, we also found that USP21 binds to two other RLR family members (MDA5 and LGP2) and deubiquitinates MDA5, suggesting USP21 acts as a major negative regulator to restrict RLR mediated antiviral responses through deubiquitinating RIG-I and MDA5."
✎
sparser
"Overexpression studies in HEK293T cells revealed that USP21 might also bind and deubiquitinate MDA5 by removing K63-linked polyubiquitination, thus inhibiting IFN-β, NF-κB, and IFN-stimulated response element (ISRE) reporter activities."
✎
sparser
"However, the interaction of USP25 with MDA5 has not been established and might be an important aspect to explore."
✎
reach
"Overexpression studies in HEK293T cells revealed that USP21 might also bind and deubiquitinate MDA5 by removing K63 linked polyubiquitination, thus inhibiting IFN-beta, NF-kappaB, and IFN stimulated response element (ISRE) reporter activities."
✎
sparser
"Indeed, overexpression of USP21 WT but not C221A mutant inhibited Lys63-linked polyubiquitination of MDA5 and MDA5-mediated IFN-β, NF-κB, and ISRE reporter activities (unpublished data) and USP21 could also bind to MDA5 and LGP2 (unpublished data)."
✎
sparser
"To study whether HDAC11 was regulated by deubiquitinating enzymes, we conducted immunoprecipitation and identified that USP25 was associated with HDAC11 ( xref )."
✎
sparser
"In this study, we identified that 1 ) CSE reduced an unstable protein HDAC11 in BEAS-2B cells, 2 ) USP25 interacted with HDAC11 and deubiquitinated HDAC11 at sites K50 and K280, 3 ) CSE-mediated USP25 polyubiquitination and subsequent degradation, and 4 ) CSE impaired defensive abilities to P. aeruginosa invasion via USP25/HDAC11 signaling in BEAS-2B cells ( xref )."
✎
reach
"Ectopic expression of USP25 rescued the USP25 siRNA led decrease of HDAC11 protein to an untreated level, suggesting that USP25 specifically regulated the protein stability of HDAC11 (XREF_FIG)."
✎
reach
"Silence of USP25 led to a decrease of HDAC11 as the overexpression of USP25 increased HDAC11 at protein level (XREF_FIG and XREF_FIG)."
✎
sparser
"Using antibodies to various TRAF for immunoprecipitation revealed that USP25 interacted with TRAF5 and TRAF6, but not with TRAF3 in HBECs or MEFs after IL-17 stimulation, while TNF stimulation induced neither USP25-TRAF5, USP25-TRAF6 nor USP25-TRAF3 association ( xref and data not shown)."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"USP25 interacts with TRAF5 and TRAF6 and deubiquitinates Act1-mediated K63-linked ubiquitination of TRAF5 and TRAF6, thereby turning off IL-17 signaling."
✎
sparser
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6 and USP25 induced removal of Act1-mediated K63-linked ubiquitination in TRAF5 and TRAF6."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6, and the USP25 deubiquitination activity opposed the activity of the Act1 E3 ubiquitin ligase, which ubiquitinates Lys63 in both TRAF5 and TRAF6."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"Furthermore, we found that TRAF-USP25 interaction depended on Act1, as Act1 deficiency impaired their association ( xref ), indicating that Act1 was required for USP25 to engage TRAF5 and TRAF6 in the IL-17 pathway."
✎
sparser
"However, we repeated this experiment with a larger dose escalation of myc-ZNF598 relative to myc-USP21 and did not observe a consistent decrease in exogenous USP21 expression as ZNF598 expression increased ( xref )."
✎
sparser
"Expression vectors containing Flag-tagged GATA3 (Flag-GATA3) and Myc-tagged USP21 (Myc-USP21) were co-transfected into HEK 293T cells."
✎
sparser
"Flag-GSC was pulled down together with Myc-USP21 ( xref ), indicating that that the two proteins interact."
✎
sparser
"Co-immunoprecipitation assays showed the interaction between the cMyc- and GFP-tagged USP25 proteins, indicating that USP25 formed homodimeric or oligomeric complexes in vivo ( xref )."
✎
sparser
"As detailed in xref , quantification of the exogenous USP21 and ZNF598 protein levels in manuscript Figure 3—figure supplement 2C revealed a decrease in myc-USP21 levels at the highest level of myc-ZNF598 plasmid expression ( xref )."
✎
sparser
"Myc-USP21 was immunoprecipitated with anti-Myc antibody and GATA3 was immunoprecipitated with anti-Flag antibody, and it was found that USP21 and Flag-GATA3 were co-immunoprecipitated ( xref )."
✎
sparser
"This was abrogated upon addition of Myc-USP21, indicating that USP21 is a DUB of GSC."
✎
sparser
"To determine whether USP21 interacts with GSC, HEK 293T cells were co-transfected with expression vectors encoding Flag epitope-tagged GSC (Flag-GSC) and Myc-tagged USP21 (Myc-USP21), followed by reciprocal co-IP."
✎
sparser
"To determine whether USP21 is a DUB of GSC, HEK 293T cells were co-transfected with Flag-GSC and HA-ubiquitin-K0 (HA-Ub-K0), with or without Myc-USP21 and Myc-WWP2; after 2 days, immunoprecipitation was performed using an anti-Flag antibody, and immunoblotting was performed with anti-HA and anti-Flag antibodies."
✎
sparser
"Compared to CYLD, VRK2 kinase-mediated phosphorylation of USP25 at residues Thr680, Thr727, and Ser745 also suppresses the deubiquitinating activity of USP25 ( xref ) ( xref )."
✎
sparser
"VRK2 kinase-mediated phosphorylation of USP25 suppressed the deubiquitinating activity of USP25 and stabilized the molecular chaperone TRiC ( xref ), leading to the aggregation of misfolded proteins in neurodegenerative diseases ( xref ; xref )."
✎
reach
"Our previous study demonstrates that USP25 is phosphorylated and inhibited by VRK2."
✎
rlimsp
"Here, we report that USP25 is a novel TRiC interacting protein that is also phosphorylated by VRK2."
✎
rlimsp
"Notably, USP25 deubiquitinating activity was suppressed when VRK2 phosphorylated the Thr(680), Thr(727), and Ser(745) residues."
✎
reach
"The interaction between USP21 and CUL3 is most likely indirect and mediated through KCTD6 given that a functional BTB domain is both required and sufficient (XREF_FIG A, C, D)."
✎
sparser
"The interaction between USP21 and CUL3 is most likely indirect and mediated through KCTD6 given that a functional BTB domain is both required and sufficient ( xref A,C,D)."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
sparser
"We asked whether USP21 interacts with a fully assembled KCTD6–CUL3 ligase complex."
E3_Ub_ligase binds USP25, KCTD6, and CUL3. 1 / 1
|
1
✎
sparser
"Having shown above that the catalytic domain of USP21 also interacts with the KCTD6–CUL3 E3-ligase complex, we wondered whether KCTD6 would be able to influence Gli1 stability in this setting."
✎
sparser
"Using antibodies to various TRAF for immunoprecipitation revealed that USP25 interacted with TRAF5 and TRAF6, but not with TRAF3 in HBECs or MEFs after IL-17 stimulation, while TNF stimulation induced neither USP25-TRAF5, USP25-TRAF6 nor USP25-TRAF3 association ( xref and data not shown)."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"USP25 interacts with TRAF5 and TRAF6 and deubiquitinates Act1-mediated K63-linked ubiquitination of TRAF5 and TRAF6, thereby turning off IL-17 signaling."
✎
sparser
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6 and USP25 induced removal of Act1-mediated K63-linked ubiquitination in TRAF5 and TRAF6."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6, and the USP25 deubiquitination activity opposed the activity of the Act1 E3 ubiquitin ligase, which ubiquitinates Lys63 in both TRAF5 and TRAF6."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"Furthermore, we found that TRAF-USP25 interaction depended on Act1, as Act1 deficiency impaired their association ( xref ), indicating that Act1 was required for USP25 to engage TRAF5 and TRAF6 in the IL-17 pathway."
✎
reach
"The interaction between USP21 and CUL3 is most likely indirect and mediated through KCTD6 given that a functional BTB domain is both required and sufficient (XREF_FIG A, C, D)."
✎
sparser
"The interaction between USP21 and CUL3 is most likely indirect and mediated through KCTD6 given that a functional BTB domain is both required and sufficient ( xref A,C,D)."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
sparser
"We asked whether USP21 interacts with a fully assembled KCTD6–CUL3 ligase complex."
E3_Ub_ligase binds USP25, KCTD6, and CUL3. 1 / 1
|
1
✎
sparser
"Having shown above that the catalytic domain of USP21 also interacts with the KCTD6–CUL3 E3-ligase complex, we wondered whether KCTD6 would be able to influence Gli1 stability in this setting."
✎
reach
"To determine whether USP21 can promote the deubiquitination of endogenous BRCA2 and/or the BRCA2 associated RAD51 and PALB2 proteins XREF_BIBR, XREF_BIBR, we measured the extent of (poly-) ubiquitin modifications on either protein in the presence or absence of USP21 overexpression."
✎
reach
"We now show that USP21 interacts with and deubiquitinates BRCA2 and that USP21 loss results in decreased BRCA2 expression in tumor cell lines."
✎
reach
"USP21 interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51 loading at DNA double-strand breaks."
✎
reach
"USP21 interacts with, and stabilises the BRCA2–RAD51 complex by antagonising degradative BRCA2 ubiquitination."
✎
sparser
"Biochemical dissection suggests that USP21 can associate with the C-terminal OB domains of BRCA2, and consistent with this, a tumor cell line with a C-terminal BRCA2 truncation is unresponsive to USP21 depletion with regard to BRCA2 stability and tumor growth (Figs. xref d and xref )."
Valproic acid affects USP25
7
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Valproic acid increases the amount of USP25. 7 / 7
7
|
✎
reach
"By conducting co-immunoprecipitation experiments from cells, we found that exogenous USP25 interacts with the ER-resident ubiquitin ligase HRD1 and with endogenous VCP and p97 (XREF_FIG)."
✎
reach
"Since USP25 interacted with VCP and p97, USP25 might deubiquitinate ERAD substrates while they are bound by VCP and p97."
✎
reach
"Sequence analyses did not identify areas indicative of a direct interaction between USP25 and VCP and p97 (not shown)."
✎
reach
"Since USP25 interacted with VCP and p97, USP25 might deubiquitinate ERAD substrates while they are bound by VCP and p97."
✎
reach
"Because USP25 also interacts with endogenous VCP and p97 (XREF_FIG), we investigated the effect of USP25 on the ubiquitination status of endogenous proteins associated with VCP and p97."
✎
reach
"Because USP25 also interacts with endogenous VCP and p97 (XREF_FIG), we investigated the effect of USP25 on the ubiquitination status of endogenous proteins associated with VCP and p97."
✎
reach
"Sequence analyses did not identify areas indicative of a direct interaction between USP25 and VCP and p97 (not shown)."
USP25 affects activity
|
7
USP25 inhibits activity.
|
6
✎
sparser
"Both USP21 and A20 inhibited SeV- and RIG-I-CARD–induced IFN-β reporter activity in a dose-dependent manner."
✎
sparser
"In this screening, USP18 and USP21 significantly inhibited RIG-I-CARD–induced IFN-β reporter activity, whereas other USPs had no effect or fewer effects ( xref )."
✎
sparser
"In contrast, mutation of S539 had little effect on the binding of mUSP21 to RIG-1 ( xref ) and the inhibition of RIG-I activity by USP21 ( xref )."
✎
sparser
"USP21 inhibited SeV-induced IFN-β reporter activity in WT, A20 −/− , ITCH −/− , and TAXBP1 −/− MEFs ( xref )."
✎
sparser
"USP21 also inhibited RIG-I-CARD–induced IFN-β reporter activity in WT, A20 −/− , ITCH −/− , and TAXBP1 −/− MEFs (unpublished data)."
✎
sparser
"Likewise, overexpression of GFP–USP21 inhibited Gli1 transcriptional activity to a similar degree, and this inhibition depended on its catalytic activity ( xref C)."
USP25 activates activity.
|
1
✎
reach
"By conducting co-immunoprecipitation experiments from cells, we found that exogenous USP25 interacts with the ER-resident ubiquitin ligase HRD1 and with endogenous VCP and p97 (XREF_FIG)."
✎
reach
"Since USP25 interacted with VCP and p97, USP25 might deubiquitinate ERAD substrates while they are bound by VCP and p97."
✎
reach
"Sequence analyses did not identify areas indicative of a direct interaction between USP25 and VCP and p97 (not shown)."
✎
reach
"Since USP25 interacted with VCP and p97, USP25 might deubiquitinate ERAD substrates while they are bound by VCP and p97."
✎
reach
"Because USP25 also interacts with endogenous VCP and p97 (XREF_FIG), we investigated the effect of USP25 on the ubiquitination status of endogenous proteins associated with VCP and p97."
✎
reach
"Because USP25 also interacts with endogenous VCP and p97 (XREF_FIG), we investigated the effect of USP25 on the ubiquitination status of endogenous proteins associated with VCP and p97."
✎
reach
"Sequence analyses did not identify areas indicative of a direct interaction between USP25 and VCP and p97 (not shown)."
✎
reach
"Mechanistically, USP25 deubiquitinated retinoic acid inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor mediated IFN signaling."
✎
reach
"In addition, wild-type USP25 significantly inhibits ubiquitination of RIG-I, TRAF2, and TRAF6, which is essential for activation of type I IFN signaling."
✎
reach
"We observed that overexpression of USP25 significantly inhibited ubiquitination of RIG-I (Figure 7B), TRAF2 (Figure 7D), and TRAF6 (Figure 7E)."
✎
reach
"We observed that overexpression of USP25 significantly inhibited ubiquitination of RIG-I (XREF_FIG), TRAF2 (XREF_FIG), and TRAF6 (XREF_FIG)."
✎
sparser
"As shown in D, USP25 indeed binds directly to SUMO and, again, more efficiently with SUMO3."
✎
sparser
"Taking the spatial location of structural motifs in the Usp25 UBR into account, here we raise the hypothesis that not only the covalent conjugation but also the non-covalent binding of SUMO to Usp25 w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
reach
"Taking the spatial location of structural motifs in the Usp25 UBR into account, here we raise the hypothesis that not only the covalent conjugation but also the non covalent binding of SUMO to Usp25 w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
sparser
"To examine whether USP25 directly interacts with SUMO or requires a bridging factor, we expressed and purified full-length untagged USP25 from bacteria (C) and incubated it with immobilized SUMO1 or S[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
reach
"As shown in Figure 1 D, USP25 indeed binds directly to SUMO and, again, more efficiently with SUMO3.To define which residues of USP25 are involved in the interaction with SUMO, we generated a series o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
sparser
"Our data suggest inhibition of Usp25's catalytic activity upon the non-covalent binding of SUMO2 to the Usp25 SUMO-interacting motif."
USP25 affects activation
|
6
✎
sparser
"USP21 inhibits virus-induced IRF3 activation via binding to and deubiquitinating RIG-I. Genetic deletion of USP21 in primary MEFs, peritoneal macrophages (PMs), and BM–derived dendritic cells (BMDCs) enhances virus- and RIG-I CARD domain (RIG-I-CARD)–induced IRF3 activation, IFN-α/β production, and antiviral response."
✎
sparser
"To further confirm that USP25 inhibited the LPS-induced activation of NF-κB and MAPKs, we performed electrophoretic mobility shift assays (EMSAs) with 32 P-labeled consensus NF-κB and AP-1 (c-Jun–c-Fos) probes and showed that a deficiency in USP25 potentiated LPS-induced, but not poly(I:C)-induced, activation of the transcription factors NF-κB and AP-1 ( xref )."
✎
sparser
"USP21 inhibits NF-kB activation through the deubiquitylation of RIPK1 [ xref ]."
✎
sparser
"Our data showed that USP21 also inhibited cGAS-induced STING-IFNβ activation in a catalytic activity-dependent manner ( xref )."
✎
sparser
"USP21 inhibits RIG-I-CARD–mediated IRF3 activation and negatively regulates antiviral response."
✎
sparser
"Collectively, these data demonstrate that USP25 inhibits LPS-induced activation of NF-κB and promotes LPS-induced activation of IRF3, which is critical for the balanced production of proinflammatory cytokines and type I IFNs upon TLR4 activation."
USP25 activates USP25.
|
3
✎
reach
"Interestingly, we also noticed that co-expression of MEK1 CA and ERK resulted in the band shift of both Nanog and USP21 (XREF_SUPPLEMENTARY), which is possibly caused by the phosphorylation of Nanog and USP21 by the activated ERK."
✎
reach
"Importantly, GST pull-down assay showed that phosphorylation of USP21 by activated p38 significantly enhanced the binding of USP21 to the purified STING (XREF_FIG)."
✎
reach
"The overexpression of USP25 downregulated IFN-beta promoter activity and IFN-beta expression in SeV infected HEK293T cells, and the silencing of USP25 by siRNA enhanced the IFN-beta promoter activity [XREF_BIBR]."
USP25 inhibits USP25.
|
1
USP25 decreases the amount of USP25.
|
1
✎
reach
"The input tagged proteins were verified with the indicated antibodies.doi: 10.1371/journal.pone.0080976.g002 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.orgdoi: 10.1371/journal.pone.0080976.g003 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org manner."
✎
reach
"However, the catalytic mutants (C178A and H607A) devoid of DUB activity lost the ability of USP25 WT-mediated IFN inhibition to some degree, indicating that DUB activity is involved in USP25 inhibition of type I IFN induction.To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"However, the catalytic mutants (C178A and H607A) devoid of DUB activity lost the ability of USP25 WT-mediated IFN inhibition to some degree, indicating that DUB activity is involved in USP25 inhibition of type I IFN induction.Sequence for siRNAs of human USP25."
✎
reach
"*P < 0.05 for all pairwise comparisons by one-way ANOVA followed by Dunnett's multiple comparisons test.doi: 10.1371/journal.pone.0080976.g006 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.orgUSP25 deubiquitinates RIG-I, TRAF2 and TRAF6."
✎
reach
"To examine whether the inhibitory effects of USP25 on SEV-induced type I IFN signaling is due to its deubiquitinase activity, wild-type USP25 (USP25-WT) and its mutants (C178A and H607A) lacking DUB activity were co-transfected with the promoter luciferase reporter plasmid of IFN-β, IRF3, NF-κB and ISRE, and the luciferase activity was detected."
✎
reach
"doi: 10.1371/journal.pone.0080976.g005 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org 7B), TRAF2 (Figure 7D), and TRAF6 (The deubiquitinating activity of USP25 is involved in virus-induced type I IFN signaling."
✎
reach
"Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65."
✎
reach
"The results showed that overexpression of USP25 downregulated SEV induced phosphorylation of IRF3 and p65 (XREF_FIG)."
✎
reach
"Overexpression of USP25 inhibited virus induced activation of IFN-beta, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-kappaB), as well as the phosphorylation of IRF3 and NF-kappaB subunit p65."
✎
reach
"The results showed that overexpression of USP25 downregulated SEV-induced phosphorylation of IRF3 and p65 (Figure 3C and D)."
✎
sparser
"Based on the fact that NLR signaling pathway components were repressed upon USP21 depletion, and USP21 was associated with relA, it is likely USP21 is a positive regulator of the NF-κB signaling pathway in TNBC cells."
✎
sparser
"It was also observed that USP21 was associated with relA, implying a link between USP21 and NF-κB in regulating NLR signaling and TNBC progression."
USP25 affects Neoplasm Metastasis
|
6
USP25 activates Neoplasm Metastasis. 6 / 6
|
6
✎
reach
"A study by Chen et al. reported that USP21 promoted cell proliferation and metastasis in bladder cancer via deubiquitinating EZH2 and stabilizing it."
✎
reach
"Subsequently, transwell assay and wound healing assay confirmed that USP21 promoted BC cells metastasis."
✎
reach
"In bladder cancer, USP21 is highly expressed and patients with high expression levels have poor survival, and USP21 can accelerate the proliferation and metastasis of bladder cancer cells via inhibiting EZH2 ubiquitination."
✎
reach
"USP21 promotes cell proliferation and metastasis through suppressing EZH2 ubiquitination in bladder carcinoma."
✎
reach
"Another study showed that USP21 expression is upregulated in bladder tumors and suggested that USP21 could promote cancer growth and metastasis by inhibiting the ubiquitylation of EZH2 in bladder cancer cell lines [XREF_BIBR]."
✎
reach
"In short, our results indicate that decreased expression of USP25 inhibits human NSCLC cell metastasis in vivo."
✎
reach
"In this study, we found that overexpression of USP25 negatively regulated IL-17- but not TNF triggered signaling."
✎
reach
"Targeting USP25 may modulate responses to IL-17, and could be beneficial in certain types of infections and cancers."
✎
reach
"These results indicate that USP25 restricts IL17 mediated pulmonary inflammation in vivo."
✎
reach
"These data together suggest that USP25 restricts IL-17 and IL-17F signaling in various types of cells."
✎
sparser
"Real-time RT-PCR analysis showed that overexpression of USP25 inhibited IL-17- but not TNF-induced expression of Cxcl1 and Il6 mRNA in HeLa cells and in 293T-IL-17RA/C cells ( xref and xref )."
✎
reach
"Unlike USP33, which has been reported to inhibit mitogen activated protein kinase (MAPK) activation pathway and suppress hepatoma cell growth 26, our study suggests that USP21 activates ERK1/2 to promote HCC cell proliferation."
✎
sparser
"Unlike USP33, which has been reported to inhibit mitogen-activated protein kinase (MAPK) activation pathway and suppress hepatoma cell growth xref , our study suggests that USP21 activates ERK1/2 to promote HCC cell proliferation."
✎
reach
"Moreover, USP21 could promote the malignant transformation of the normal human hepatocytes and increased the tumorigenicity of the HCC cells by activating the ERK signaling through the stabilization of MEK2."
✎
sparser
"Using antibodies to various TRAF for immunoprecipitation revealed that USP25 interacted with TRAF5 and TRAF6, but not with TRAF3 in HBECs or MEFs after IL-17 stimulation, while TNF stimulation induced neither USP25-TRAF5, USP25-TRAF6 nor USP25-TRAF3 association ( xref and data not shown)."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"USP25 interacts with TRAF5 and TRAF6 and deubiquitinates Act1-mediated K63-linked ubiquitination of TRAF5 and TRAF6, thereby turning off IL-17 signaling."
✎
sparser
"Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6 and USP25 induced removal of Act1-mediated K63-linked ubiquitination in TRAF5 and TRAF6."
✎
sparser
"Mechanistically, IL-17 stimulation induced the association of USP25 with TRAF5 and TRAF6, and the USP25 deubiquitination activity opposed the activity of the Act1 E3 ubiquitin ligase, which ubiquitinates Lys63 in both TRAF5 and TRAF6."
✎
reach
"9 At the transcriptional level, the expression of USP21 in mESCs was activated by the LIF and STAT3 pathway, which was critical for the maintenance of mESC and the self-renewal of mESCs."
✎
reach
"At the transcriptional level, the expression of USP21 in mESCs was activated by the LIF and STAT3 pathway, which was critical for the maintenance of mESC and the self-renewal of mESCs."
✎
reach
"In accordance with these results, treatment with Cryptotanshinone, a specific inhibitor of STAT3 by inhibiting STAT3 Y705 phosphorylation, reduced the expression of USP21 (XREF_SUPPLEMENTARY)."
✎
reach
"Moreover, the expression of exogenous STAT3 effectively activated USP21 promoter driven luciferase expression in a dose dependent manner (XREF_FIG), whereas mutating the core STAT3 binding sequence (TGCTTCCCC to TGCCCACCC) within the USP21 promoter abolished the effect of STAT3 (XREF_FIG)."
✎
reach
"Indeed, overexpression of USP21 WT but not C221A mutant inhibited Lys63 linked polyubiquitination of MDA5 and MDA5 mediated IFN-beta, NF-kappaB, and ISRE reporter activities (unpublished data) and USP21 could also bind to MDA5 and LGP2 (unpublished data)."
✎
reach
"Furthermore, we also found that USP21 binds to two other RLR family members (MDA5 and LGP2) and deubiquitinates MDA5, suggesting USP21 acts as a major negative regulator to restrict RLR mediated antiviral responses through deubiquitinating RIG-I and MDA5."
✎
sparser
"Overexpression studies in HEK293T cells revealed that USP21 might also bind and deubiquitinate MDA5 by removing K63-linked polyubiquitination, thus inhibiting IFN-β, NF-κB, and IFN-stimulated response element (ISRE) reporter activities."
✎
sparser
"However, the interaction of USP25 with MDA5 has not been established and might be an important aspect to explore."
✎
reach
"Overexpression studies in HEK293T cells revealed that USP21 might also bind and deubiquitinate MDA5 by removing K63 linked polyubiquitination, thus inhibiting IFN-beta, NF-kappaB, and IFN stimulated response element (ISRE) reporter activities."
✎
sparser
"Indeed, overexpression of USP21 WT but not C221A mutant inhibited Lys63-linked polyubiquitination of MDA5 and MDA5-mediated IFN-β, NF-κB, and ISRE reporter activities (unpublished data) and USP21 could also bind to MDA5 and LGP2 (unpublished data)."
✎
reach
"Importantly, we go on to show that either depletion or overexpression of USP21 suppresses Gli1 dependent transcription in human cells."
✎
reach
"Intriguingly, overexpression of USP21 represses Gli1 dependent transcription, despite the fact that the total amount of Gli1 is clearly increased."
✎
reach
"Importantly, we show that both depletion and overexpression of catalytically active USP21 suppress Gli1 dependent transcription."
✎
sparser
"USP21 is able to interact with GLI1, thereby suppressing GLI1-dependent transcription."
✎
sparser
"Whereas we cannot exclude that some aspects of exogenous Gli1-activation rely on primary cilium formation, taken together, our data showing (1) an interaction between USP21 and Gli1, (2) the regulation of PKA-dependent phosphorylation of Gli1 by USP21, and (3) the colocalisation of all three proteins at the centrosome in U2OS cells make a strong case for a regulatory role of USP21 that could be independent of cilium formation."
CGAS affects USP25
|
5
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, xref – xref and found that USP25 and USP29 interacted with cGAS in such a system (Fig. xref )."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, [35] [36] [37] and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a) ."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established,35–37 and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a)."
Barium(2+) affects USP25
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3
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Barium(2+) inhibits USP25. 5 / 5
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3
2
✎
sparser
"In addition, BA also inhibited USP21 in LNCaP and 22Rv1 cells and a partial knockdown of USP21 resulted in a strong reduction of AR protein (Fig. xref )."
✎
reach
"DUB labeling with HA-UbVS showed that BA treatment of LNCaP and 22Rv1 cells inhibited active USP21."
✎
reach
"In addition, BA also inhibited USP21 in LNCaP and 22Rv1 cells and a partial knockdown of USP21 resulted in a strong reduction of AR protein."
USP25 affects signaling
|
5
✎
sparser
"Next, we examined whether USP21 and A20 can cooperatively inhibit antiviral signaling."
✎
sparser
"Conversely, deubiquitinating enzymes such as CYLD, ubiquitin-specific protease (USP)3, and USP21 inhibit RIG-I-mediated immune signaling by removing the K63 ubiquitin chain from RIG-I protein xref – xref ."
✎
sparser
"Overexpression of USP25 inhibited IL-17-triggered signaling, whereas USP25 deficiency resulted in more phosphorylation of the inhibitor IκBα and kinase Jnk and higher expression of chemokines and cytokines, as well as a prolonged half-life for chemokine CXCL1-encoding mRNA after treatment with IL-17."
✎
sparser
"Overexpression of USP25 inhibited IL-17-triggered signaling, while USP25 deficiency resulted in increased phosphorylation of IκBα and Jnk, increased expression of chemokines and cytokines as well as prolonged half-life of Cxcl1 mRNA following IL-17 treatment."
✎
sparser
"By contrast, USP21 inhibits TNF-α-induced NF-κB signaling by promoting the deubiquitination of receptor-interacting protein 1 (RIP1) in HeLa cells ( xref )."
USP25 affects inflammatory response
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5
USP25 inhibits inflammatory response.
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3
USP25 inhibits inflammatory response. 3 / 3
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3
✎
reach
"These results indicate that USP25 restricts IL17 mediated pulmonary inflammation in vivo."
✎
reach
"IL-17-mediated inflammation is also attenuated by USP25 through TRAF5 and TRAF6 deubiquitination [66]."
✎
reach
"Ubiquitin specific peptidase 25 alleviates acute lung injury and suppresses the inflammatory response in lung epithelial cells."
USP25 activates inflammatory response.
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2
USP25 activates inflammatory response. 2 / 2
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2
USP25 affects cGAS
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5
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, xref – xref and found that USP25 and USP29 interacted with cGAS in such a system (Fig. xref )."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, [35] [36] [37] and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a) ."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established,35–37 and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a)."
✎
reach
"Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling."
✎
reach
"For example, USP21 deubiquitinates receptor interacting protein kinase 1 (RIP1) and repress the signaling transduction activity downstream of TNFalpha receptor 1 (TNFR1) and NFkappaB pathway [XREF_BIBR]."
✎
reach
"Notably, Usp21 fl/fl Lyz2-cre mice produced significantly higher concentrations of IFNbeta, IL-6, and TNF in serum upon HSV-1 infection compared with infected control mice (XREF_FIG)."
✎
reach
"Consistently, Usp21 deficiency resulted in production of more IFNbeta and TNF in MEFs and BMDMs in response to HSV-1 infection (XREF_FIG)."
✎
sparser
"The measured K d value for the interaction between the Usp25 UBR and SUMO2 is 9.40 ± 0.72 μ M ( Fig. 4 C ), which is consistent with our NMR spectral observations."
✎
sparser
"Our data suggest inhibition of Usp25's catalytic activity upon the non-covalent binding of SUMO2 to the Usp25 SUMO-interacting motif."
USP25 affects ISRE
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1
4
✎
eidos
"Knockdown of USP25 gene also led to augmentation of ISRE promoter upon SeV induction [ 20 ] ."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV induced activation of IFN-beta (XREF_FIG), IRF3 (XREF_FIG), NF-kappaB (XREF_FIG) and ISRE (XREF_FIG) in a dose dependent manner."
✎
reach
"Because IFN-beta reporter activity is dependent on both NF-kappaB and IRF3, we further tested the inhibitory effect of USP21 on SeV-, RIG-I-CARD-, and TBK1 induced NF-kappaB and ISRE reporter activities."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β (Figure 6A), IRF3 (Figure 6B), NF-κB (Figure 6C) and ISRE (Figure 6D) in a dose-dependent manner."
USP25 affects ISRE reporter
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5
✎
reach
"Interestingly, we found that overexpression of USP21 WT but not C221A mutant inhibited IFN-beta, NF-kappaB, and ISRE reporter activities in HEK293T cells in response to transfected poly (I : C), which was known to be mediated by MDA5 (unpublished data), suggesting that USP21 might also target MDA5."
✎
reach
"They unveiled that USP21 inhibited ISRE reporter activity induced by SeV and RIG-I-CARD, but not by TANK binding kinase 1 (TBK1) in mouse embryonic fibroblasts (MEF) cells [XREF_BIBR]."
✎
reach
"ISRE reporter activity was also inhibited by USP25 in a dose-dependent manner [20]."
✎
reach
"They unveiled that USP21 inhibited ISRE reporter activity induced by SeV and RIG-I-CARD, but not by TANK-binding kinase 1 (TBK1) in mouse embryonic fibroblasts (MEF) cells [24]."
✎
reach
"ISRE reporter activity was also inhibited by USP25 in a dose dependent manner [XREF_BIBR]."
USP25 affects GC
|
5
✎
reach
"These results demonstrated that USP21 stimulated cell proliferation, migration, invasion, and stemness of GC cells."
✎
reach
"Furthermore, it was also proved in nude mice that overexpression of USP21 stimulated the tumor growth and cell stemness of GC in vivo."
✎
reach
"The results disclosed that overexpression of USP21 remarkably elevated the expression levels of CD44 and CD133 in GC tissue (XREF_FIG), indicating that overexpression of USP21 enhanced the stemness of GC cells."
✎
reach
"We reported that USP21 promoted GC cell proliferation, migration, invasion, and stemness in vitro, and regulated GC tumor growth and cell stemness in mice in vivo."
✎
reach
"Further investigation showed that USP21 downregulates cyclin T1 mRNA levels by increasing methylation of histone K9 in the promoter of cyclin T1, a subunit of the positive transcription elongation factor b (P-TEFb) that interacts with Tat and transactivation response element (TAR) and is required for transcription stimulation and Tat stability."
✎
reach
"Further investigation showed that USP21 downregulates cyclin T1 mRNA levels by increasing methylation of histone K9 in the promoter of cyclin T1, a subunit of the positive transcription elongation factor b (P-TEFb) that interacts with Tat and transactivation response element (TAR) and is required for transcription stimulation and Tat stability."
✎
reach
"First, USP21 deubiquitinates polyubiquitinated Tat causing Tat instability, and second USP21 reduces the mRNA levels of cyclin T1 (CycT1), an important component of P-TEFb, that leads 56 to Tat downregulation."
✎
reach
"First, USP21 deubiquitinates polyubiquitinated Tat causing Tat instability, and second USP21 reduces the mRNA levels of cyclin T1 (CycT1), an important component of P-TEFb, that leads 56 to Tat downregulation."
✎
reach
"Overexpression of USP25 in hippocampus promoted the neural stem cells to glial cell fates and suppressed neuronal cell fate by altering the balance between cyclin D1 and cyclin D2, thus reducing neurogenesis in the hippocampus."
✎
sparser
"The measured K d value for the interaction between the Usp25 UBR and SUMO2 is 9.40 ± 0.72 μ M ( Fig. 4 C ), which is consistent with our NMR spectral observations."
✎
sparser
"Our data suggest inhibition of Usp25's catalytic activity upon the non-covalent binding of SUMO2 to the Usp25 SUMO-interacting motif."
✎
sparser
"USP21 interacts with RIP1 and deubiquitinates RIP1 in a DUB-dependent manner ( xref )."
✎
sparser
"To explore the possible functional interactions between USP21 and RIPK1 in these pathways, we derived macrophages and dendritic cells from the bone marrow of Usp21 -/- and wild types age-matched control mice, and compared their responses to TLR3, TLR4 and TNFR stimulation."
✎
reach
"To explore the possible functional interactions between USP21 and RIPK1 in these pathways, we derived macrophages and dendritic cells from the bone marrow of Usp21 -/- and wild types age matched control mice, and compared their responses to TLR3, TLR4 and TNFR stimulation."
✎
sparser
"USP21 is constitutively associated with RIP1 and deubiquitinates RIP1 in vitro and in vivo."
✎
reach
"At the post-translational level, USP21 was phosphorylated by ERKs induced by differentiation cues."
✎
reach
"At the post-translational level, USP21 was phosphorylated by ERKs induced by differentiation cues."
✎
sparser
"Interestingly, we also noticed that co-expression of MEK1 CA and ERK resulted in the band shift of both Nanog and USP21 ( xref ), which is possibly caused by the phosphorylation of Nanog and USP21 by the activated ERK."
✎
sparser
"At the post-translational level, USP21 was phosphorylated by ERKs induced by differentiation cues."
✎
sparser
"At the post-translational level, USP21 was phosphorylated by ERKs induced by differentiation cues."
MiR-200c affects USP25
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4
MiR-200c inhibits USP25.
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2
MiR-200c activates USP25.
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2
✎
reach
"Hence, it appears that miR-200c negatively regulates tumor metastasis in NSCLC patients by targeting USP25."
✎
reach
"To determine if miR-200c directly targets the 3 ' UTRs of USP25, PKIA, and SMURF2, we constructed vectors containing the full-length wild-type or mutant 3 '-UTR of USP25, PKIA, SMURF2 directly fused to the downstream of the firefly luciferase gene."
✎
reach
"Here, we screened a series of USP members and found that USP21 inhibits HIV-1 production by specifically targeting Tat, but not the other HIV-1 accessory proteins."
✎
reach
"USP21 deubiquitylates Tat via its deubiquitinase activity, but a stronger ability to reduce Tat expression compared to Ub-KO showed that other mechanisms may contribute to USP21 mediated inhibition of Tat."
USP25 affects cell differentiation
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4
USP25 activates cell differentiation. 4 / 4
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4
✎
reach
"Depletion of USP21 promoted the differentiation of mESCs and reduced the efficiency of somatic cell reprogramming."
✎
reach
"Reintroduction of USP21 efficiently rescued the mESC differentiation caused by USP21 depletion, but failed to rescue mESC differentiation caused by Nanog knockdown (XREF_FIG)."
✎
reach
"Similarly, USP21 and OTUD3 antagonized the ZNF598-dependent eS10 ubiquitylation in uS10-KI cells in an activity dependent manner."
✎
reach
"DUBs in the RQC pathway have begun to be explored, as a recent study showed that among 58 DUBs screened, overexpression of either USP21 or OTUD3 in mammalian cells can cause the removal of ZNF598-specific ribosomal ubiquitination [145]."
✎
reach
"Taken together, these results indicate that USP21 or OTUD3 can deubiquitylate both eS10 and uS10, resulting in enhanced readthrough of poly(A)-mediated stall events."
✎
reach
"USP21 and OTUD3 antagonize the ubiquitination of eS10 and uS10 that results from integrated stress response (ISR) and ribosome-associated quality control pathway (RQC) (124)."
✎
reach
"Exogenous expression of USP21 substantially reduced the ZNF598-stimulated eS10 and uS10 ubiquitylation in an activity-dependent manner (Figure 3E)."
USP25 affects Nasopharyngeal Carcinoma
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4
USP25 activates Nasopharyngeal Carcinoma. 4 / 4
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4
✎
reach
"Sphere formation assay was performed on nasopharyngeal carcinoma cells after knockdown of USP21, which revealed that knockdown of USP21 inhibited the stemness profiles of nasopharyngeal carcinoma cells."
✎
reach
"CCK-8 and EdU immunofluorescent staining assays revealed that USP21 promoted the proliferation of nasopharyngeal carcinoma cells."
✎
reach
"These findings proved that USP21 promoted tumor growth and cancer cell stemness in nasopharyngeal carcinoma by regulating FOXM1."
✎
sparser
"In addition, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells ( xref ) and that knockdown of TRAF3 or TRAF6 had no effect on the LPS-induced recruitment of USP25 to TLR4 ( xref )."
✎
reach
"In this regard, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells."
✎
sparser
"In this regard, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells."
✎
reach
"In addition, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells (XREF_SUPPLEMENTARY) and that knockdown of TRAF3 or TRAF6 had no effect on the LPS induced recruitment of USP25 to TLR4 (XREF_SUPPLEMENTARY)."
USP25 affects ISRE promoter
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4
USP25 inhibits ISRE promoter.
|
3
✎
reach
"The results suggest that overexpression of USP25 strongly inhibited SEV induced activation of ISRE promoter in a dose dependent manner (XREF_FIG)."
✎
reach
"The results suggest that overexpression of USP25 strongly inhibited SEV-induced activation of ISRE promoter in a dose-dependent manner (Figure 1B)."
✎
reach
"HEK-293T cells were transfected with ISRE reporter plasmid USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org The results suggest that overexpression of USP25 strongly inhibited SEV-induced activation of ISRE promoter in a dosedependent manner ( Figure 1B) ."
USP25 activates ISRE promoter.
|
1
✎
reach
"USP25’s DUB activity was also found to be necessary for virus-induced signaling, as USP25 knockdown MEFs with WT USP25 reconstitution allowed expression of Ifnb, Ifna4 and IL-6 upon SeV or HSV-1 induction, while those with DUB activity mutant USP25 did not [21]."
✎
reach
"USP25 's DUB activity was also found to be necessary for virus induced signaling, as USP25 knockdown MEFs with WT USP25 reconstitution allowed expression of Ifnb, Ifna4 and IL-6 upon SeV or HSV-1 induction, while those with DUB activity mutant USP25 did not [XREF_BIBR]."
✎
sparser
"In addition, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells ( xref ) and that knockdown of TRAF3 or TRAF6 had no effect on the LPS-induced recruitment of USP25 to TLR4 ( xref )."
✎
reach
"In this regard, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells."
✎
sparser
"In this regard, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells."
✎
reach
"In addition, we found that USP25 interacted with MyD88, but not TRIF, in coimmunoprecipitation studies of transfected cells (XREF_SUPPLEMENTARY) and that knockdown of TRAF3 or TRAF6 had no effect on the LPS induced recruitment of USP25 to TLR4 (XREF_SUPPLEMENTARY)."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
sparser
"We asked whether USP21 interacts with a fully assembled KCTD6–CUL3 ligase complex."
E3_Ub_ligase binds USP25, KCTD6, and CUL3. 1 / 1
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1
✎
sparser
"Having shown above that the catalytic domain of USP21 also interacts with the KCTD6–CUL3 E3-ligase complex, we wondered whether KCTD6 would be able to influence Gli1 stability in this setting."
✎
sparser
"To study whether HDAC11 was regulated by deubiquitinating enzymes, we conducted immunoprecipitation and identified that USP25 was associated with HDAC11 ( xref )."
✎
sparser
"In this study, we identified that 1 ) CSE reduced an unstable protein HDAC11 in BEAS-2B cells, 2 ) USP25 interacted with HDAC11 and deubiquitinated HDAC11 at sites K50 and K280, 3 ) CSE-mediated USP25 polyubiquitination and subsequent degradation, and 4 ) CSE impaired defensive abilities to P. aeruginosa invasion via USP25/HDAC11 signaling in BEAS-2B cells ( xref )."
✎
sparser
"This work proposes that in Tregs, USP21, GATA3, and FOXP3 may form a positive loop to promote FOXP3 expression and thus modulate Treg activity."
✎
sparser
"Thus, USP21, GATA3, and FOXP3 could form a positive loop in promoting FOXP3 expression that in turns modulates Treg cell activity ( xref )."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
sparser
"We asked whether USP21 interacts with a fully assembled KCTD6–CUL3 ligase complex."
E3_Ub_ligase binds USP25, KCTD6, and CUL3. 1 / 1
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1
✎
sparser
"Having shown above that the catalytic domain of USP21 also interacts with the KCTD6–CUL3 E3-ligase complex, we wondered whether KCTD6 would be able to influence Gli1 stability in this setting."
Trichostatin A affects USP25
3
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CGAS affects USP29
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3
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, xref – xref and found that USP25 and USP29 interacted with cGAS in such a system (Fig. xref )."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, [35] [36] [37] and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a) ."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established,35–37 and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a)."
Bisphenol A affects USP25
3
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Bisphenol A decreases the amount of USP25.
2
|
Bisphenol A methylates USP25.
1
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USP29 affects cGAS
|
3
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, xref – xref and found that USP25 and USP29 interacted with cGAS in such a system (Fig. xref )."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, [35] [36] [37] and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a) ."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established,35–37 and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a)."
USP25 affects ubH2A
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3
✎
reach
"Besides, USP21 could promote transcription by deubiquitylating ubH2A in vitro [XREF_BIBR]."
✎
reach
"The USP21 short variant (USP21SV) lacking NES, located mostly in the nucleus in vivo, activates transcription by deubiquitylating ubH2A in vitro."
✎
reach
"Furthermore, both recombinant USP21 variants activate transcription by deubiquitylating ubH2A in vitro."
USP25 affects transcription, DNA-templated
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3
USP25 inhibits transcription, DNA-templated.
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2
USP25 inhibits transcription, DNA-templated. 2 / 2
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2
✎
reach
"USP21 is able to interact with GLI1, thereby suppressing GLI1 dependent transcription."
✎
reach
"Here, we demonstrate that the deubiquitinase, USP21, potently inhibits HIV-1 production by indirectly downregulating the expression of HIV-1 trans-activator of transcription (Tat), which is essential for transcriptional elongation in HIV-1."
USP25 activates transcription, DNA-templated.
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1
USP25 activates transcription, DNA-templated. 1 / 1
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1
✎
reach
"We identified that USP21 deubiquitylates nucleosomal ubH2A in the nucleus and activates transcription XREF_BIBR."
USP25 affects synaptic function 5xFAD mice
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3
✎
eidos
"Inhibition of USP25 reestablishes homeostatic microglial signatures and restores synaptic and cognitive function in 5xFAD mice ."
| PMC
✎
eidos
"To determine whether Usp25 deficiency restores synaptic function in 5xFAD mice , we measured hippocampal LTP and found that it was compromised in 5xFAD compared with WT and Usp25 + / - mice ; however , 5xFAD-associated LTP impairment was reversed in 5xFAD ; Usp25 + / - mice ( Fig. 3 , G and H ) ."
| PMC
✎
eidos
"Inhibition of USP25 reestablishes homeostatic microglial signatures and restores synaptic and cognitive function in 5xFAD mice ."
USP25 affects polyubiquitination
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3
✎
sparser
"Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus–induced RIG-I polyubiquitination and RIG-I–mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection."
✎
sparser
"Interestingly, in our in vitro assay, USP21 deubiquitinates RIG-I-CARD, whereas A20 fails to do so, even though both USP21 and A20 inhibit RIG-I-CARD overexpression-induced RIG-I-CARD polyubiquitination in vivo ( xref )."
✎
sparser
"Furthermore, polyubiquitinated RIG-I mediated by RNF135 can be deubiquitinated by USP21 but not A20 in vitro even though both USP21 and A20 inhibit RNF135-induced RIG-I polyubiquitination in vivo ( xref )."
✎
sparser
"Taken together, our results demonstrate that PCV2 infection activates the p38-MAPK signaling pathway-mediated USP21 phosphorylation to inhibit the K63 ubiquitination of STING, which prevents the phosphorylation and transportation to the nucleus of IRF3, leading to an increase risk for PPV infection."
USP25 affects lipopolysaccharide
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3
USP25 activates lipopolysaccharide. 3 / 3
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3
✎
reach
"To further confirm that USP25 inhibited the LPS induced activation of NF-kappaB and MAPKs, we performed electrophoretic mobility shift assays (EMSAs) with 32 P labeled consensus NF-kappaB and AP-1 (c-Jun-c-Fos) probes and showed that a deficiency in USP25 potentiated LPS induced, but not poly (I : C)-induced, activation of the transcription factors NF-kappaB and AP-1 (XREF_FIG)."
✎
reach
"A deficiency in USP25 potentiated LPS induced, but not poly (I : C)-induced, activation of NF-kappaB and MAPKs, as well as the production of proinflammatory cytokines."
✎
reach
"Because USP25 interacted with TRAF3 after stimulation with LPS and because the enzyme activity of USP25 was required for its regulation of TLR4 signaling (XREF_FIG and XREF_FIG), we hypothesized that USP25 might target TRAF3 for deubiquitination in response to LPS."
USP25 affects initiation
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3
✎
sparser
"In vitro , we found that ubH2A inhibits H3 lysine 4 methylation and proved that USP21 activates transcript initiation by permitting H3 lysine 4 methylation through deubiquitylating ubH2A xref ."
✎
sparser
"USP21 has been reported to deubiquitinate histone H2A and activate transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation during hepatocyte regeneration xref ."
✎
sparser
"Furthermore, we found that USP21 activates transcript initiation using in vitro reconstituted chromatin xref , xref , xref ."
USP25 affects homologous recombination
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3
USP25 activates homologous recombination. 3 / 3
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3
✎
reach
"Deactivation of USP21 reduces the HR activity and increases the DNA damage frequency [XREF_BIBR]."
✎
reach
"Cells overexpressing USP21 increased HR efficiency, and cells defective of USP21 showed a significant decrease in HR [33]."
| PMC
✎
reach
"Notably, tumor associated SCNAs often result from non allelic homologous recombination events 49, consistent with our observation that USP21 positively regulates HR."
USP25 affects cell migration
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3
USP25 activates cell migration.
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2
USP25 activates cell migration. 2 / 2
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2
USP25 inhibits cell migration.
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1
USP25 inhibits cell migration. 1 / 1
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1
✎
reach
"Knockdown of USP25 by siRNA in A549, H1299, and SPC-A-1sci cells inhibited cell migration and invasion in vitro, which fell to levels similar to those observed after transfection with the miR-200c mimics."
USP25 affects cell death
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3
USP25 activates cell death. 3 / 3
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3
✎
reach
"PDAC is characterized by a severely hypoxic microenvironment, and USP25 depletion abrogates HIF-1α transcriptional activity and impairs glycolysis, inducing PDAC cell death in the tumor hypoxic core."
✎
reach
"In this report, we found that PdPT is an inhibitor of multiple DUBs including USP7, USP10, USP14, USP15, USP25 and UCHL5, which contributes to the accumulation of ubiquitinated proteins and subsequent cell death in NSCLC cell lines.Regulated cell death requires activation of various regulators and effectors (23)."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, xref – xref and found that USP25 and USP29 interacted with cGAS in such a system (Fig. xref )."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established, [35] [36] [37] and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a) ."
✎
sparser
"To test this hypothesis, we conducted an unbiased screening of cGAS-interacting DUBs by cotransfection and immunoprecipitation assays as previous established,35–37 and found that USP25 and USP29 interacted with cGAS in such a system (Fig. 1a)."
✎
sparser
"We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or "hot spot," consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences."
✎
reach
"We first screened a panel of DUBs and found that both USP2 and USP21 bound to endogenous SKP2, but only USP2 deubiquitylated and stabilized SKP2 protein."
✎
reach
"In the USP2 and USP21 complex structure, the side chain of Ub Lys48 does not occupy the nearby pocket on USP (see XREF_FIG)."
✎
reach
"In the USP21-diubiquitin complex the N-terminal Ub-domain is in contact with the finger domain."
✎
sparser
"In the USP21-diubiquitin complex the N-terminal Ub-domain is in contact with the finger domain."
✎
reach
"In the USP21 and diubiquitin complex the N-terminal Ub-domain is in contact with the finger domain."
✎
sparser
"Because USP25 negatively regulates IL-17-induced activation of NF-κB and stabilization of chemokine mRNA, which involves TRAF6 and TRAF5, respectively xref , we examined whether USP25 interacts with these TRAF proteins."
✎
sparser
"Furthermore, we found that TRAF-USP25 interaction depended on Act1, as Act1 deficiency impaired their association ( xref ), indicating that Act1 was required for USP25 to engage TRAF5 and TRAF6 in the IL-17 pathway."
✎
sparser
"When we subjected membrane fractions from LPS-treated BMDMs to immunoprecipitation with an antibody against TLR4 (anti-TLR4 antibody), we observed that USP25, TRAF3, and TRAF6 were co-immunoprecipitated ( xref ), supporting the idea that LPS stimulates the formation of a membrane-bound TLR4 signaling complex consisting of USP25, TRAFs, and cIAPs."
✎
sparser
"Interestingly, USP21 inhibits both TRIM25- and RNF135-mediated antiviral response and RIG-I activation ( xref and not depicted)."
✎
sparser
"USP21 inhibits TRIM25- and RNF135-mediated RIG-I polyubiquitination and activation."
✎
sparser
"These results demonstrate that USP21 inhibits TRIM25- or RNF135-mediated RIG-I polyubiquitination and activation to negatively regulate antiviral signaling."
✎
sparser
"When we subjected membrane fractions from LPS-treated BMDMs to immunoprecipitation with an antibody against TLR4 (anti-TLR4 antibody), we observed that USP25, TRAF3, and TRAF6 were co-immunoprecipitated ( xref ), supporting the idea that LPS stimulates the formation of a membrane-bound TLR4 signaling complex consisting of USP25, TRAFs, and cIAPs."
✎
reach
"In vivo tumor xenograft model assays indicated that YY1 knockdown abolished USP21 overexpression-induced tumor growth (Fig. 2e)."
✎
reach
"PDAC is characterized by a severely hypoxic microenvironment, and USP25 depletion abrogates HIF-1α transcriptional activity and impairs glycolysis, inducing PDAC cell death in the tumor hypoxic core."
✎
reach
"These findings proved that USP21 promoted tumor growth and cancer cell stemness in nasopharyngeal carcinoma by regulating FOXM1."
✎
reach
"Consistently, IL-17- but not TNF induced phosphorylation and degradation of IkappaBalpha was impaired by overexpression of USP25 (XREF_FIG)."
✎
reach
"Overexpression of USP25 inhibited IL-17-triggered signaling, while USP25 deficiency resulted in increased phosphorylation of IkappaBalpha and Jnk, increased expression of chemokines and cytokines as well as prolonged half-life of Cxcl1 mRNA following IL-17 treatment."
✎
reach
"Overexpression of USP25 inhibited IL-17-triggered signaling, whereas USP25 deficiency resulted in more phosphorylation of the inhibitor IkappaBalpha and kinase Jnk and higher expression of chemokines and cytokines, as well as a prolonged half-life for chemokine CXCL1 encoding mRNA after treatment with IL-17."
✎
sparser
"By immunoprecipitation, we identified that HBO1 associates with a deubiquitinating enzyme USP25 in THP-1 cells."
✎
sparser
"Among the 19 deubiquitinating enzymes screened, we identified that USP25 associated with HBO1."
✎
sparser
"Results from co-immunoprecipitation studies showed that LPS does not dynamically alter HBO1-USP25 interaction ( xref )."
✎
reach
"USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1."
✎
reach
"Silencing of USP21 enhances polyubiquitination of FOXD1, promotes its proteasomal degradation, and ultimately attenuates MES identity in GSCs, while these effects could be largely restored by reintroduction of FOXD1."
✎
reach
"Amplification of USP21 deubiquitinase promotes pancreatic cancer cell growth and stemness via Wnt and beta-catenin signaling [XREF_BIBR]."
✎
reach
"This suggests that USP25 acts as a DUB of tankyrase to stabilize tankyrase and induce a positive process of Wnt and beta-catenin signaling [XREF_BIBR]."
USP25 affects CD3delta
|
3
✎
reach
"CD3delta interacts with both USP25 and HRD1 in cells (XREF_FIG), suggesting a functional interaction between HRD1 and USP25 in ERAD."
✎
reach
"According to our results, USP25 : a) interacted with and rescued the ERAD substrates CD3delta and APP, and counteracted HRD1 effects on CD3delta, b) localized in part at the ER and interacted with the ERAD components HRD1 and VCP and p97, c) reduced the levels of endogenous ubiquitinated species associated with HRD1 and VCP and p97, and d) regulated the levels of endogenous APP, as knockdown of endogenous USP25 was associated with lower levels of endogenous APP."
✎
reach
"These results together with the interaction between CD3delta and USP25 (XREF_FIG), suggest that USP25 might rescue CD3delta from proteasomal degradation by directly deubiquitinating it."
✎
sparser
"We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or "hot spot," consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences."
✎
reach
"We first screened a panel of DUBs and found that both USP2 and USP21 bound to endogenous SKP2, but only USP2 deubiquitylated and stabilized SKP2 protein."
✎
reach
"In the USP2 and USP21 complex structure, the side chain of Ub Lys48 does not occupy the nearby pocket on USP (see XREF_FIG)."
✎
reach
"In addition, USP18-mediated deISGylation in vitro is approximately 40-fold faster than deISGylation by the cross-reactive deubiquitinating enzymes (DUB) USP21 [15] raising the question whether deISGylation by Ub/ISG15 cross-reactive DUBs is relevant in vivo.Despite enhanced ISGylation, mice homozygous for USP18-C61A (USP18 ) are healthy and display a normal lifespan [27]."
✎
reach
"In addition, USP18-mediated deISGylation in vitro is approximately 40-fold faster than deISGylation by the cross-reactive deubiquitinating enzymes (DUB) USP21 [15] raising the question whether deISGylation by Ub/ISG15 cross-reactive DUBs is relevant in vivo.Despite enhanced ISGylation, mice homozygous for USP18-C61A (USP18C61A/C61A) are healthy and display a normal lifespan [27]."
✎
reach
"Moreover, USP17 is a positive regulator of RORgammat in Th17 cells, whereas USP18 has been reported to modulate T cell activation and Th17 cell differentiation by deubiquitinating of the TAK1 and TAB1 complex [XREF_BIBR] and USP25 has been regarded as a negative regulator of IL-17-mediated inflammation via TRAF5 and TRAF6 deubiquitination [XREF_BIBR]."
✎
reach
"In the USP21-diubiquitin complex the N-terminal Ub-domain is in contact with the finger domain."
✎
sparser
"In the USP21-diubiquitin complex the N-terminal Ub-domain is in contact with the finger domain."
✎
reach
"In the USP21 and diubiquitin complex the N-terminal Ub-domain is in contact with the finger domain."
✎
sparser
"Because USP25 negatively regulates IL-17-induced activation of NF-κB and stabilization of chemokine mRNA, which involves TRAF6 and TRAF5, respectively xref , we examined whether USP25 interacts with these TRAF proteins."
✎
sparser
"Furthermore, we found that TRAF-USP25 interaction depended on Act1, as Act1 deficiency impaired their association ( xref ), indicating that Act1 was required for USP25 to engage TRAF5 and TRAF6 in the IL-17 pathway."
✎
sparser
"When we subjected membrane fractions from LPS-treated BMDMs to immunoprecipitation with an antibody against TLR4 (anti-TLR4 antibody), we observed that USP25, TRAF3, and TRAF6 were co-immunoprecipitated ( xref ), supporting the idea that LPS stimulates the formation of a membrane-bound TLR4 signaling complex consisting of USP25, TRAFs, and cIAPs."
✎
sparser
"Upon infection with an RNA or DNA virus, USP25 associates with TRAF3 and TRAF6 and protects TRAF3 and TRAF6 from virus-induced proteasome-dependent or independent degradation ( xref )."
✎
sparser
"USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
✎
sparser
"USP25 interacts with RIG-I and TRAF6. (A, B) HEK-293T cells grown in 100-mm dishes were co-transfected with the indicated plasmids encoding the RIG-I (A) or TRAF6 (B) expression vector (4 μg) and HA-USP25WT/ HA-USP25C178A/ HA-USP25H607A (4 μg) using Lipofectamine 2000."
✎
sparser
"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see Figure S1 )."
✎
sparser
"Upon infection with an RNA or DNA virus, USP25 associates with TRAF3 and TRAF6 and protects TRAF3 and TRAF6 from virus-induced proteasome-dependent or independent degradation ( xref )."
✎
sparser
"USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively."
✎
sparser
"In our previous study, we demonstrated that USP25 interacts with TRAF3, TRAF5, and TRAF6 in an overexpression system in human embryonic kidney (HEK) 293T cells and that endogenous USP25-TRAF5 and USP25-TRAF6 interactions are promoted by IL-17 ( xref )."
✎
sparser
"By immunoprecipitation, we identified that HBO1 associates with a deubiquitinating enzyme USP25 in THP-1 cells."
✎
sparser
"Among the 19 deubiquitinating enzymes screened, we identified that USP25 associated with HBO1."
✎
sparser
"Results from co-immunoprecipitation studies showed that LPS does not dynamically alter HBO1-USP25 interaction ( xref )."
✎
reach
"To investigate whether USP25 regulates IL-17-mediated airway inflammation, wild-type and Usp25 -/- mice were treated with PBS or IL-17 via intranasal injection, followed by analysis of bronchoalveolar lavage fluid (BALF) and lung inflammation."
✎
reach
"Compared to wild-type cells, the expression of Cxcl1, Tnf and/or Il6 mRNA was enhanced in Usp25 -/- cells treated with IL-17 alone or in synergy with TNF but not with TNF alone (XREF_FIG)."
✎
sparser
"Further investigation will be required to identify USP25 mutants that disrupt the interaction of USP25 and RIG-I/TRAF6 but do not affect DUB activity; and to test whether these domains of USP25 interacting with RIG-I and TRAF6 also contribute to the inhibition of IFN induction by USP25."
✎
sparser
"USP25 interacts with RIG-I and TRAF6. (A, B) HEK-293T cells grown in 100-mm dishes were co-transfected with the indicated plasmids encoding the RIG-I (A) or TRAF6 (B) expression vector (4 μg) and HA-USP25WT/ HA-USP25C178A/ HA-USP25H607A (4 μg) using Lipofectamine 2000."
✎
sparser
"Indeed, co-immunoprecipitation investigation showed that USP25 interacted with RIG-I and TRAF6 (see Figure S1 )."
✎
sparser
"Taken together, our data indicate that CUL3, KCTD6 and USP21 can form a multimeric complex in which the catalytic domain of USP21 interacts with the C-terminal SmrL domain of KCTD6, whereas the BTB domain of the latter mediates interaction with CUL3 ( xref E)."
✎
sparser
"We asked whether USP21 interacts with a fully assembled KCTD6–CUL3 ligase complex."
CD3delta affects USP25
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3
✎
reach
"CD3delta interacts with both USP25 and HRD1 in cells (XREF_FIG), suggesting a functional interaction between HRD1 and USP25 in ERAD."
✎
reach
"According to our results, USP25 : a) interacted with and rescued the ERAD substrates CD3delta and APP, and counteracted HRD1 effects on CD3delta, b) localized in part at the ER and interacted with the ERAD components HRD1 and VCP and p97, c) reduced the levels of endogenous ubiquitinated species associated with HRD1 and VCP and p97, and d) regulated the levels of endogenous APP, as knockdown of endogenous USP25 was associated with lower levels of endogenous APP."
✎
reach
"These results together with the interaction between CD3delta and USP25 (XREF_FIG), suggest that USP25 might rescue CD3delta from proteasomal degradation by directly deubiquitinating it."
Potassium chromate affects USP25
2
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Phenylmercury acetate affects USP25
2
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Pentachlorophenol affects USP25
2
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2
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Lipopolysaccharide, E coli O55-B5 phosphorylates USP25.
1
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Lipopolysaccharide, E coli O55-B5 phosphorylates USP25. 1 / 1
1
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Lipopolysaccharide, E coli O55-B5 increases the amount of USP25.
1
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Lipopolysaccharide, E coli O55-B5 increases the amount of USP25. 1 / 1
1
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Hsa_circ_0039053 affects USP25
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2
✎
reach
"Mechanically, hsa_circ_0039053 positively regulated USP21 expression through interacting with miR-637."
✎
reach
"Collectively, our study confirmed that hsa_circ_0039053 could be regarded as a competing endogenous RNA (ceRNA) to positively modulate the expression of USP21 combining with miR-637, which provided a potential target in HCC treatment."
Hsa-miR-6867-5p affects USP25
2
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Hsa-miR-567 affects USP25
2
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Hsa-miR-511-3p affects USP25
2
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Hsa-miR-5011-5p affects USP25
2
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Hsa-miR-410-3p affects USP25
2
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Hsa-miR-297 affects USP25
2
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Hsa-miR-223-5p affects USP25
2
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Hsa-miR-200c-3p affects USP25
2
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Hsa-miR-190a-3p affects USP25
2
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Entinostat affects USP25
2
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Disulfiram affects USP25
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1
1
Disulfiram inhibits USP25. 2 / 2
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1
1
Cyclosporin A affects USP25
2
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Chloroquine affects USP25
2
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Chloroquine phosphorylates USP25.
1
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Chloroquine decreases the amount of USP25.
1
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All-trans-retinoic acid affects USP25
2
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✎
sparser
"The rather tight specificity of the USP25/SYK interaction is further demonstrated by the absence of any detectable interaction between ZAP70 and USP25 ( Fig. 1 A, left panel) despite a 52% identity be[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
reach
"The rather tight specificity of the USP25 and SYK interaction is further demonstrated by the absence of any detectable interaction between ZAP70 and USP25 despite a 52% identity between SYK and ZAP70 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Ubv.21.4CDelta2 affects USP25
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2
USP25 affects type I IFNs
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2
✎
reach
"Second, in TLR4 triggered innate immune cells, USP25 also promotes the TRIF dependent production of type I IFNs, a process in which TRAF3 is an essential stimulator."
✎
reach
"Consistent with these observations, LPS stimulated, K 48 -linked ubiquitination of TRAF3 was further potentiated, and the degradation of TRAF3 was accelerated in Usp25 -/- BMDMs compared to that in wild-type BMDMs, whereas reconstitution of USP25 deficient MEFs with TRAF3 inhibited the generation of proinflammatory cytokines and restored the generation of type I IFNs in response to LPS."
✎
eidos
"Together , these results indicate that USP25 deficiency suppresses microglia-mediated proinflammatory cytokine production and synapse elimination by targeting WDFY1 and ATP6V0C , respectively ( fig ."
| PMC
✎
eidos
"Mechanistically , USP25 deficiency attenuates microglia-mediated proinflammatory cytokine overproduction and synapse elimination ."
| PMC
USP25 affects response
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2
USP25 affects reporter
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1
1
✎
eidos
"ISRE reporter activity was also inhibited by USP25 in a dose-dependent manner [ 20 ] ."
✎
reach
"Nuclear localization of YAP increased significantly in BJ cells depleted of USP21, compared to the control cells, consistent with the observation that USP21 inhibition increased YAP reporter activity and transcriptional expression of YAP target genes."
USP25 affects protein deubiquitination
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2
USP25 activates protein deubiquitination. 2 / 2
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2
✎
eidos
"TRAF6 mediated deubiquitination by USP25 and A20 mediate the negative feedback regulation of IL-17 induced NFkappaB and MAPK ."
✎
eidos
"Recently , it has been shown that USP25 directly interacts with tankyrases through its C-terminal tail and promotes their deubiquitination and stabilization , thus regulating Wnt / beta-catenin signaling pathway , making an important impact in cell proliferation and human cancer development28 ."
USP25 affects microglia-mediated proinflammatory cytokine overproduction
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2
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β (Figure 6A), IRF3 (Figure 6B), NF-κB (Figure 6C) and ISRE (Figure 6D) in a dose-dependent manner."
USP25 affects macropinocytosis
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2
USP25 activates macropinocytosis. 2 / 2
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2
✎
reach
"USP21 deubiquitinase elevates macropinocytosis to enable oncogenic KRAS bypass in pancreatic cancer."
✎
reach
"1327-1332) identify one such mechanism in which the deubiquitinase USP21 up-regulates the nutrient-scavenging process of macropinocytosis, rescuing PDAC cells from Kras extinction."
USP25 affects innate immune response
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2
USP25 inhibits innate immune response.
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1
USP25 inhibits innate immune response. 1 / 1
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1
✎
reach
"These results suggest that USP25 indeed negatively regulates the antiviral innate immune response."
USP25 activates innate immune response.
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1
USP25 activates innate immune response. 1 / 1
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1
✎
reach
"Thus, by inhibiting the degradation of TRAF3 during TLR4 activation, USP25 enables a balanced innate immune response."
USP25 affects immune response
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2
USP25 inhibits immune response. 2 / 2
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2
✎
reach
"USP2b, USP3, USP18, USP25, UL36USP and HAUSP play a role of antivirus; while USP4, USP13, USP15 and USP17 negatively regulate antiviral immune response."
✎
reach
"Therefore, we speculated that the absence of USP21 might inhibit the Th17-type immune response, which exerted a positive effect on the reduction of liver immunopathological damage and might also lead to immune dysfunction in the host."
USP25 affects growth factor
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2
USP25 activates growth factor. 2 / 2
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2
✎
reach
"In addition, USP21 knockdown in PC12 cells inhibits nerve growth factor induced neurite outgrowth suggesting its role associated with microtubules XREF_BIBR."
✎
reach
"Our functional studies indicate a key role for USP21 in the governance of microtubule- and centrosome associated physiological processes : Depletion of USP21 in A549 cells compromises the reestablishment of a radial array of microtubules during recovery from cold induced depolymerization and also reduces the probability of primary cilium formation, whereas USP21 knockdown in PC12 cells inhibits nerve growth factor induced neurite outgrowth."
USP25 affects glycolytic process
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1
USP25 activates glycolytic process. 2 / 2
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1
1
✎
eidos
"PDAC is characterized by a severely hypoxic microenvironment , and USP25 depletion abrogates HIF-1alpha transcriptional activity and impairs glycolysis , inducing PDAC cell death in the tumor hypoxic core ."
✎
reach
"PDAC is characterized by a severely hypoxic microenvironment, and USP25 depletion abrogates HIF-1α transcriptional activity and impairs glycolysis, inducing PDAC cell death in the tumor hypoxic core."
USP25 affects cell cycle
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2
USP25 activates cell cycle. 2 / 2
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2
✎
reach
"Altogether, these findings strengthen the idea that USP21 promotes cell cycle progression and tumor growth by stabilizing MEK2 and thereby activating ERK1/2 signaling."
✎
reach
"These results demonstrate that USP21 promotes cell proliferation by inducing cell cycle progression in HL-7702 and MHCC97L cell lines."
USP25 affects activities
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2
✎
sparser
"USP21 inhibited TRIM25-mediated IFN-β reporter activities, which was also inhibited by CYLD and A20, but the deubiquitinase activity of A20 was not required ( xref and not depicted)."
✎
sparser
"Furthermore, human USP21 inhibited SeV-induced IFN-β reporter activities in MEFs whereas mouse USP21 inhibited SeV-induced IFN-β reporter activities in HEK293T cells ( xref and not depicted), suggesting that USP21 function in antiviral signaling is not limited by cell type and is conserved between human and mouse."
✎
sparser
"The rather tight specificity of the USP25/SYK interaction is further demonstrated by the absence of any detectable interaction between ZAP70 and USP25 ( Fig. 1 A, left panel) despite a 52% identity be[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
✎
reach
"The rather tight specificity of the USP25 and SYK interaction is further demonstrated by the absence of any detectable interaction between ZAP70 and USP25 despite a 52% identity between SYK and ZAP70 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP25 affects Treg signature genes
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2
✎
reach
"In addition, USP21 prevents the depletion of FOXP3 protein by mediating its deubiquitination and thereby maintaining the expression of Treg signature genes and Treg specific deficiency of Usp21 contributed to the development of Th1-type inflammation [XREF_BIBR]."
✎
reach
"166 Treg specific deletion of USP21 in mice reduces the level of Foxp3 and perturbs the expression of Treg signature genes, causing aberrant T cell activation and autoimmune symptoms."
✎
reach
"Then, USP21 prevents Foxp3 degradation, which further enhances the transcription of Usp21 and suppresses Th1 like phenotypes."
✎
reach
"Furthermore, another study showed that the depletion of USP21 induces the production of Th1 like Tregs as a result of unstable FOXP3 expression, leading to severe autoimmune systemic disorders [XREF_BIBR]."
USP25 affects TBK1-NF-kappaB
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2
✎
reach
"Usp25 deficiency in macrophages enhances TBK1-NF-kappaB signaling, and the induction of inflammatory chemokines and type I interferon-related genes exacerbates pancreatic and lung injury in AP."
✎
reach
"Similarly, in vitro data confirm that Usp25 deficiency enhances the TBK1-NF-kappaB pathway, leading to increased expression of inflammatory cytokines in bone marrow-derived macrophages."
✎
reach
"53 However, Usp25 deficiency in our study increased TBK1 phosphorylation but failed to change the TBK1 protein levels, indicating that USP25 does not affect TBK1 protein stability or deubiquitination."
✎
reach
"Our results show that expression of Usp25 in Usp25 BMDMs largely reverses ACS-induced phosphorylation of TBK1, IRF3, and P65 (Figure 5A)."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [ xref ]."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [111]."
USP25 affects SNHG16
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2
✎
sparser
"Fig. 16: Co-crystal DUB structures using diUb-ABPs. (A) USP21 bound to Met1 diUb ABP that contains a terminal aldehyde warhead (PDB: 2Y5B). (B) SARS PLpro in complex with a triazole linked K48 diUb ABP that contains a terminal propargyl warhead (PDB: 5E6J). (C) Cezanne/OTUD7B in complex with K11 diUb-ABP that contains an internal Michael acceptor warhead (PDB: 5LRV)."
| PMC
✎
sparser
"Co-crystal DUB structures using diUb-ABPs. (A) USP21 bound to Met1 diUb ABP that contains a terminal aldehyde warhead (PDB: 2Y5B). (B) SARS PLpro in complex with a triazole linked K48 diUb ABP that contains a terminal propargyl warhead (PDB: 5E6J). (C) Cezanne/OTUD7B in complex with K11 diUb-ABP that contains an internal Michael acceptor warhead (PDB: 5LRV)"
| PMC
USP25 affects SERCA2a
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2
✎
reach
"In addition, we overexpressed USP25 and SERCA2a in the heart with adenoassociated virus serotype 9 vectors to validate the biological function of USP25 and SERCA2a interaction."
✎
reach
"Mechanistically, USP25 bound to SERCA2a directly via its USP (ubiquitin-specific protease) domain and cysteine at position 178 of USP25 exerts deubiquitination to maintain the stability of the SERCA2a protein by removing the K48 ubiquitin chain and preventing proteasomal pathway degradation, thereby maintaining calcium handling in cardiomyocytes."
✎
reach
"Ablation of USP21 in skeletal muscle promotes oxidative fibre phenotype, inhibiting obesity and type 2 diabetes."
✎
reach
"Consequently, USP21 ablation diminished diet-induced obesity (WT vs. USP21-KO, Δ8.02 g, 17.1%, P < 0.01; litter vs. USP21-MKO, Δ3.48 g, 7.7%, P < 0.05) and insulin resistance."
USP25 affects NSCLC
|
2
✎
reach
"No evidence was presented to support TRIM25 or USP21 mediated GLTSCR2 removal of K63-linked polyubiquitin chains from RIG-I.In this work, we presented evidence that viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm, and cytoplasmic translocation enabled GLTSCR2 to effectively attenuate IFN-β and support viral replication; however, viral infection did not result in elevating GLTSCR2 in cells."
✎
reach
"No evidence was presented to support TRIM25 or USP21 mediated GLTSCR2 removal of K63 linked polyubiquitin chains from RIG-I."
✎
reach
"Overexpression of USP25 inhibited IL-17-triggered signaling, while USP25 deficiency resulted in increased phosphorylation of IkappaBalpha and Jnk, increased expression of chemokines and cytokines as well as prolonged half-life of Cxcl1 mRNA following IL-17 treatment."
✎
reach
"Overexpression of USP25 inhibited IL-17-triggered signaling, whereas USP25 deficiency resulted in more phosphorylation of the inhibitor IkappaBalpha and kinase Jnk and higher expression of chemokines and cytokines, as well as a prolonged half-life for chemokine CXCL1 encoding mRNA after treatment with IL-17."
✎
reach
"USP25 's DUB activity was also found to be necessary for virus induced signaling, as USP25 knockdown MEFs with WT USP25 reconstitution allowed expression of Ifnb, Ifna4 and IL-6 upon SeV or HSV-1 induction, while those with DUB activity mutant USP25 did not [XREF_BIBR]."
✎
reach
"USP25’s DUB activity was also found to be necessary for virus-induced signaling, as USP25 knockdown MEFs with WT USP25 reconstitution allowed expression of Ifnb, Ifna4 and IL-6 upon SeV or HSV-1 induction, while those with DUB activity mutant USP25 did not [21]."
USP25 affects IFN-I
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2
USP25 affects Hypertrophy
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2
USP25 inhibits Hypertrophy. 2 / 2
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2
✎
reach
"Moreover, restoration of USP25 expression via adenoassociated virus serotype 9 vectors in USP25 -/- mice attenuated Ang II-induced cardiac hypertrophy and cardiac dysfunction, whereas myocardial overexpression of SERCA2a could mimic the effect of USP25."
✎
reach
"We confirmed that USP25 inhibited cardiac hypertrophy by deubiquitinating and stabilizing SERCA2a."
✎
reach
"TNKS1 expression levels were found to be considerably repressed in USP25-knockdown glioma cells and elevated in USP25-overexpressed glioma cells, accompanied by Wnt/ β -catenin pathway key protein downregulation and upregulation, respectively."
✎
reach
"Glioma cell invasion, migration, and proliferation activity were dramatically inhibited in USP25-knockdown glioma cells and promoted in USP25-overexpressed glioma cells."
USP25 affects Figure 6B
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2
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reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β ( Figure 6A ), IRF3 ( Figure 6B ), NF-κB ( Figure 6C ) and ISRE ( Figure 6D ) in a dose-dependent To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."
✎
reach
"The results showed that USP25-WT remarkably inhibited SEV-induced activation of IFN-β (Figure 6A), IRF3 (Figure 6B), NF-κB (Figure 6C) and ISRE (Figure 6D) in a dose-dependent manner."
USP25 affects DNA Damage
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2
USP25 inhibits DNA Damage.
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1
USP25 inhibits DNA Damage. 1 / 1
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"USP25 inhibits DNA damage by stabilizing BARD1 protein in a house dust mite-induced asthmatic model in vitro and in vivo."
USP25 activates DNA Damage.
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USP25 activates DNA Damage. 1 / 1
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1
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reach
"As a result, depletion of USP21 decreases homologous recombination efficiency, causes an increase in DNA damage load and impairs tumor cell survival."
USP25 affects ChFP
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2
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reach
"USP21 or OTUD3 overexpression in either eS10-KI or uS10-KI cells resulted in a further enhancement of the ChFP:GFP ratio above the respective transfection controls (Figure 4C,D)."
✎
reach
"OTUB2, OTUD3, USP10 and UCHL1 expression did not alter the ChFP:GFP ratio of the control reporter while OTUD1 and USP21 only modestly elevated the ChFP:GFP ratio indicating that the identified Dubs specifically alter the ability of ribosomes to progress through a poly(A)-induced ribosomal stall (Figure 3B)."
USP25 affects BCR-ABL protein
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2
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reach
"We further found that pharmacological inhibition of USP25 induced rapid degradation of BCR-ABL protein in Ph positive leukemia cells, regardless of their sensitivity to tyrosine kinase inhibitors."
✎
reach
"Deubiquitylase USP25 prevents degradation of BCR-ABL protein and ensures proliferation of Ph positive leukemia cells."
USP25 affects Ala-Gly-Ser
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USP25 activates Ala-Gly-Ser. 2 / 2
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reach
"Afterward, the role of USP21 in cell migration and invasion was evaluated through Transwell assay, and the data in XREF_FIG showed that overexpression of USP21 accelerated the migration and invasion of AGS cells, whereas knockdown of USP21 pronouncedly reduced the migration and invasion of MKN-45 cells."
✎
reach
"To further determine the role of USP21 in the growth and maintenance of CSCs, the sphere forming capability of AGS cells treated with oe-USP21 or of MKN-45 cells treated with si-USP21 was studied."
USP25 affects AP AP-related organ injury
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2
✎
eidos
"Moreover , USP25 expression was upregulated in cerulein-induced AP in mice , while USP25 deficiency attenuates AP and AP-related multiple organ injury ."
✎
eidos
"We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 ( STAT3 ) pathway ."
USP25 affects 5xFAD mice
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2
✎
eidos
"Together , these results indicate that disruptions in excitation / inhibition signaling in 5xFAD mouse hippocampus can be restored by Usp25 haploinsufficiency ( Fig. 3I ) , and demonstrate that USP25 down-regulation reverses synaptic and cognitive deficits in 5xFAD mice ."
| PMC
✎
sparser
"Upon infection with an RNA or DNA virus, USP25 associates with TRAF3 and TRAF6 and protects TRAF3 and TRAF6 from virus-induced proteasome-dependent or independent degradation ( xref )."
✎
sparser
"USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [ xref ]."
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sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [111]."
SNHG16 affects USP25
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2
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reach
"A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500."
✎
reach
"We found that YY1 bound to the SNHG16 promoter region and transcriptionally upregulated the expression of SNHG16, which increased the expression level of USP21 through miR-4500."
✎
reach
"Additionally, Smurf1 mediated degradation of USP25 is via promoting the K48-linkage polyubiquitination of USP25 in an ubiquitin proteasome dependent pathway."
✎
reach
"Smurf1 overexpression decreases USP25 protein turnover, and the E3 ligase enzymatic activity of Smurf1 is required for USP25 degradation."
✎
sparser
"Fig. 16: Co-crystal DUB structures using diUb-ABPs. (A) USP21 bound to Met1 diUb ABP that contains a terminal aldehyde warhead (PDB: 2Y5B). (B) SARS PLpro in complex with a triazole linked K48 diUb ABP that contains a terminal propargyl warhead (PDB: 5E6J). (C) Cezanne/OTUD7B in complex with K11 diUb-ABP that contains an internal Michael acceptor warhead (PDB: 5LRV)."
| PMC
✎
sparser
"Co-crystal DUB structures using diUb-ABPs. (A) USP21 bound to Met1 diUb ABP that contains a terminal aldehyde warhead (PDB: 2Y5B). (B) SARS PLpro in complex with a triazole linked K48 diUb ABP that contains a terminal propargyl warhead (PDB: 5E6J). (C) Cezanne/OTUD7B in complex with K11 diUb-ABP that contains an internal Michael acceptor warhead (PDB: 5LRV)"
| PMC
SERCA2a affects USP25
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2
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reach
"In addition, we overexpressed USP25 and SERCA2a in the heart with adenoassociated virus serotype 9 vectors to validate the biological function of USP25 and SERCA2a interaction."
✎
reach
"Mechanistically, USP25 bound to SERCA2a directly via its USP (ubiquitin-specific protease) domain and cysteine at position 178 of USP25 exerts deubiquitination to maintain the stability of the SERCA2a protein by removing the K48 ubiquitin chain and preventing proteasomal pathway degradation, thereby maintaining calcium handling in cardiomyocytes."
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sparser
"Based on the fact that NLR signaling pathway components were repressed upon USP21 depletion, and USP21 was associated with relA, it is likely USP21 is a positive regulator of the NF-κB signaling pathway in TNBC cells."
✎
sparser
"It was also observed that USP21 was associated with relA, implying a link between USP21 and NF-κB in regulating NLR signaling and TNBC progression."
✎
reach
"At the transcriptional level, the expression of USP21 in mESCs was activated by the LIF and STAT3 pathway, which was critical for the maintenance of mESC and the self-renewal of mESCs."
✎
reach
"9 At the transcriptional level, the expression of USP21 in mESCs was activated by the LIF and STAT3 pathway, which was critical for the maintenance of mESC and the self-renewal of mESCs."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [ xref ]."
✎
sparser
"While USP21 and Stub1 directly interact with FOXP3, the E3 ubiquitin ligase VHL indirectly regulates Th1-like Treg generation by increasing the expression of HIF-1α, which binds to the IFNG promoter, increasing IFNγ production [111]."
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2
EC 3.5.1.98 (histone deacetylase) inhibitor decreases the amount of USP25. 2 / 2
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reach
"To verify our observation in the BEAS-2B cells, we observed that CSE decreased both USP25 and HDAC11 at the protein levels in both concentration and time course studies in human primary small airway epithelial cells (XREF_FIG and XREF_FIG)."
✎
reach
"These data suggested that CSE degraded USP25, as well as HDAC11, in lung epithelial cells."
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reach
"In the ABPP assay, AZ1 strongly blocked labeling of USP25 by DUB ABP, however, it had little impact on USP28."
✎
sparser
"We observed biochemical inhibition of USP25 and USP28 by AZ1 with IC 50 s of 3.47 ± 0.73 μM (n = 4) and 0.98 ± 0.02 μM (n = 2) respectively, in line with reported values for the compound."
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Vismodegib affects USP25
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1
Vismodegib binds USP25. 1 / 1
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1
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reach
"Furthermore, cellular assays were conducted to confirm that Vismodegib could interact with the evolutionarily related deubiquitinases USP28 and USP25 and down-regulate the levels of the two enzymes ' substrate proteins c-Myc, Notch1 and Tankyrase-1/2."
Sodium arsenite affects USP25
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Polyubiquitin affects USP25
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1
Motif affects USP25
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1
Monoubiquitin affects USP25
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1
Mono(2-ethylhexyl) phthalate affects USP25
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Mono(2-ethylhexyl) phthalate decreases the amount of USP25. 1 / 1
1
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MiR-4500 affects USP25
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1
MiR-27a-3p affects USP25
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Methylmercury chloride affects USP25
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Methylmercury chloride increases the amount of USP25. 1 / 1
1
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Interaction affects USP25
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1
Inserts domain molecule tetramer affects USP25
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1
Hsa-miR-513a-5p affects USP25
1
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Hsa-miR-411-5p affects USP25
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Hsa-miR-27a-3p affects USP25
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Hsa-miR-216a-3p affects USP25
1
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Hsa-miR-144-3p affects USP25
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Hsa-miR-128-3p affects USP25
1
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Endoplasmic reticulum affects USP25
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Endoplasmic reticulum inhibits USP25. 1 / 1
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reach
"USP25 was decreased in CHO cells treated with ER stress inducers, whereas HRD1 and BiP were increased."
Dorsomorphin affects USP25
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Dicrotophos affects USP25
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Cycloheximide affects USP25
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1
Cycloheximide activates USP25. 1 / 1
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reach
"To assess the effect of USP21 on FOXM1 half-life, FOXM1 levels were assessed by IB following overexpression of either USP21 WT or USP21 C221A in 293T cells (XREF_FIG) and depletion of USP21 in BLBC MDA-MB-231 cells (XREF_SUPPLEMENTARY) treated with cycloheximide to block protein translation."
Bis(2-chloroethyl) sulfide affects USP25
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Bis(2-chloroethyl) sulfide increases the amount of USP25. 1 / 1
1
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Amiodarone affects USP25
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Acrylamide affects USP25
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sparser
"When we subjected membrane fractions from LPS-treated BMDMs to immunoprecipitation with an antibody against TLR4 (anti-TLR4 antibody), we observed that USP25, TRAF3, and TRAF6 were co-immunoprecipitated ( xref ), supporting the idea that LPS stimulates the formation of a membrane-bound TLR4 signaling complex consisting of USP25, TRAFs, and cIAPs."
Ubvs affects USP25
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1
Ubv21.4 affects USP25
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1
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reach
"Furthermore, the median root mean square deviations of the MD, CONCOORD, and Backrub backbones were 0.63, 0.53, and 0.28 A, respectively, to the wild-type ubiquitin structure (PDB ID : 3I3T) and were 0.64, 0.57, and 0.37 A, respectively, to Ubv21.4, a known variant that tightly binds USP21 (PDB ID : 3MTN)."
Ubv affects USP25
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1
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USP25 affects vismodegib
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Vismodegib binds USP25. 1 / 1
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1
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reach
"Furthermore, cellular assays were conducted to confirm that Vismodegib could interact with the evolutionarily related deubiquitinases USP28 and USP25 and down-regulate the levels of the two enzymes ' substrate proteins c-Myc, Notch1 and Tankyrase-1/2."
USP25 affects virus-induced IFN
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1
USP25 affects type I interferons
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1
USP25 affects translation
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1
USP25-C221A inhibits translation. 1 / 1
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1
✎
reach
"To assess the effect of USP21 on FOXM1 half-life, FOXM1 levels were assessed by IB following overexpression of either USP21 WT or USP21 C221A in 293T cells (XREF_FIG) and depletion of USP21 in BLBC MDA-MB-231 cells (XREF_SUPPLEMENTARY) treated with cycloheximide to block protein translation."
USP25 affects transcription ISGs
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1
USP25 affects stabilization
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1
USP25 affects polyubiquitin
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1
USP25 affects polyubiquitin chains
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1
USP25 affects poly
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1
USP25 affects pathology IL-17-dependent experimental autoimmune encephalomyelitis EAE
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1
USP25 affects oe-USP21
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1
USP25 affects monoubiquitin
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1
USP25 affects miR-4500
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1
USP25 affects isopeptidase
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USP25 affects induced IFN-beta
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1
USP25 affects function
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1
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1
USP25 inhibits epithelial to mesenchymal transition. 1 / 1
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1
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reach
"Knockdown of USP25 suppressed the EMT process, the invasion and migration capability of trophoblast cells, while overexpression of USP25 exhibited opposite results."
USP25 affects energy homeostasis
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1
USP25 activates energy homeostasis. 1 / 1
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1
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reach
"The outcomes of this research provide novel information as to how USP21 in skeletal muscle contributes to systemic energy homeostasis, demonstrating USP21 as a key molecule in the regulation of myofibre type switch, muscle mass control, mitochondrial function, and heat generation and, thus, implicating the potential of this molecule and its downstream substrates network as targets for the treatment and/or prevention of muscle dysfunction and the associated metabolic diseases."
USP25 affects degradation
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1
USP25 affects beta cleavage APP Abeta
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1
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sparser
"When we subjected membrane fractions from LPS-treated BMDMs to immunoprecipitation with an antibody against TLR4 (anti-TLR4 antibody), we observed that USP25, TRAF3, and TRAF6 were co-immunoprecipitated ( xref ), supporting the idea that LPS stimulates the formation of a membrane-bound TLR4 signaling complex consisting of USP25, TRAFs, and cIAPs."
USP25 affects Ubv21.4
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1
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reach
"Furthermore, the median root mean square deviations of the MD, CONCOORD, and Backrub backbones were 0.63, 0.53, and 0.28 A, respectively, to the wild-type ubiquitin structure (PDB ID : 3I3T) and were 0.64, 0.57, and 0.37 A, respectively, to Ubv21.4, a known variant that tightly binds USP21 (PDB ID : 3MTN)."
USP25 affects Ubv.21.4CDelta2
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1
USP25 affects Ubv
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1
USP25 affects Trisomy 21-induced microglial homeostasis brains
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1
USP25 affects TNKS-ARC5 protein
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1
USP25 affects TLR4 signaling-induced innate immune responses
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1
USP25 affects TGFβ-SMAD
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1
USP25 affects TCF/LEF
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1
USP25 affects RIG-I MDA5-dependent IFN signaling
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1
USP25 affects Proteasome
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1
USP25 activates Proteasome. 1 / 1
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reach
"Therefore, in physiological conditions sumoylation would impair the rescue of substrates from proteasome degradation by USP25."
USP25 affects Pancreatitis
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1
USP25 inhibits Pancreatitis. 1 / 1
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reach
"Quantitative assessment of pancreatic injury showed that Usp25 deficiency worsens CDE-induced pancreatitis in mice (Figure 9B and C)."
USP25 affects PDAC cell death
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1
USP25 affects NLR
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1
USP25 affects MluI site
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1
USP25 affects Lys48
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1
USP25 affects K63-polyubiquitin chains
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1
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reach
"Ubiquitylation events are reversible processes, and, accordingly, several deubiquitylating enzymes, in particular ubiquitin specific peptidase 3 (USP3), USP21 and CYLD lysine 63 deubiquitinase (CYLD), modulate RIG-I signalling by removing K63-polyubiquitin chains, although with unique kinetics."
USP25 affects K63
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USP25 affects K48
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1
USP25 affects K27
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1
USP25 affects IL-17-mediated inflammation
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1
USP25 affects Hyperglycemia
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1
USP25 activates Hyperglycemia. 1 / 1
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1
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reach
"USP22 in pancreatic β-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."
USP25 affects Hemagglutinin
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USP25 binds Hemagglutinin. 1 / 1
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sparser
"g001 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org and increasing amounts of HA-USP25 expression plasmids."
✎
reach
"Our results suggest that endogenous USP21 positively regulates Hh signaling through two independent mechanisms : firstly, we have previously shown that USP21 depletion interferes with the formation of primary cilia, the specialised organelles that host the initiation of the Hh signaling cascade in untransformed mammalian cells."
USP25 affects HA-ATP6V0C HA-WDFY1
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1
USP25 affects H3K4me3
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1
USP25 affects ERAD substrate CD3delta [
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1
USP25 affects E3_Ub_ligase
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1
USP25 affects Diabetes Mellitus, Type 2
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1
USP25 inhibits Diabetes Mellitus, Type 2. 1 / 1
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1
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reach
"Ablation of USP21 in skeletal muscle promotes oxidative fibre phenotype, inhibiting obesity and type 2 diabetes."
USP25 affects Cell Survival
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1
USP25 inhibits Cell Survival. 1 / 1
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1
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reach
"As a result, depletion of USP21 decreases homologous recombination efficiency, causes an increase in DNA damage load and impairs tumor cell survival."
USP25 affects CD3delta protein
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1
USP25 affects Bacterial Infections
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1
USP25 activates Bacterial Infections. 1 / 1
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1
✎
reach
"The deubiquitinase USP25 supports colonic inflammation and bacterial infection and promotes colorectal cancer."
USP25 affects BCR-ABL
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1
USP25 affects Abeta-induced phagocytosis synapses
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1
UBL affects USP25
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1
UBA1 affects monoubiquitin
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1
✎
sparser
"When we subjected membrane fractions from LPS-treated BMDMs to immunoprecipitation with an antibody against TLR4 (anti-TLR4 antibody), we observed that USP25, TRAF3, and TRAF6 were co-immunoprecipitated ( xref ), supporting the idea that LPS stimulates the formation of a membrane-bound TLR4 signaling complex consisting of USP25, TRAFs, and cIAPs."
TRAF3 affects K48
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1
TNKS-ARC5 protein affects USP25
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1
✎
sparser
"When we subjected membrane fractions from LPS-treated BMDMs to immunoprecipitation with an antibody against TLR4 (anti-TLR4 antibody), we observed that USP25, TRAF3, and TRAF6 were co-immunoprecipitated ( xref ), supporting the idea that LPS stimulates the formation of a membrane-bound TLR4 signaling complex consisting of USP25, TRAFs, and cIAPs."
STING1 affects K27
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1
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S-2-pentyl-4-pentynoic hydroxamic acid increases the amount of USP25. 1 / 1
1
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PTM [ affects USP25
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1
NLR affects USP25
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1
MluI site affects USP25
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1
MAP2K2 affects Lys48
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1
MACE affects USP25
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1
Lys48 affects USP25
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1
KCTD6 affects E3_Ub_ligase
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1
K63 affects USP25
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1
K48 affects USP25
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1
K27 affects USP25
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1
Hemagglutinin affects USP25
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1
USP25 binds Hemagglutinin. 1 / 1
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1
✎
sparser
"g001 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org and increasing amounts of HA-USP25 expression plasmids."
E3_Ub_ligase affects USP25
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1
Dnmt1 affects monoubiquitin
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1
CUL3 affects E3_Ub_ligase, KCTD6, and USP25
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1
Aroclor 1254 affects USP25
1
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Antirheumatic Agents affects USP25
1
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Antirheumatic Agents increases the amount of USP25. 1 / 1
1
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7,12-dimethyltetraphene affects USP25
1
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7,12-dimethyltetraphene decreases the amount of USP25. 1 / 1
1
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