IndraLab

Statements

ZUP1 affects Interferon
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ZUP1 inhibits Interferon.
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ZUP1 inhibits Interferon. 10 / 16
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"For example, viral DUB activity of CCHFV OTU and equine arteritis virus OTU suppresses type I IFN signaling during infection (7–9), whereas the turnip yellow mosaic virus DUB counters Ub-mediated proteasomal degradation of its polymerase (17)."
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"These results therefore suggest that host cells lack the ability to produce type I IFN in response to MHV-A59 infection.Because ubiquitination plays an important role in the RIG-I-mediated IFN induction cascade 20, and because PLpro domain 2 (PLP2) domain of MHV-A59 contains a conserved DUB motif 22, we hypothesized that the DUB activity of PLP2 domain might block the IFNβ response during MHV-A59 infection."
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"This DUB activity may remove ubiquitin from innate immune signaling factors to suppress the induction of an antiviral state, and indeed was shown to reduce IFN signaling in biochemical experiments using PL2 pro overexpression for several coronaviruses, including SARS-CoV (Matthews et al. 2014a; ) and MERS-CoV Clementz et al. 2010; Bailey-Elkin et al. 2014) ."
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"These results therefore strongly suggested that PLP2 domain that associated with TBK1/IRF3 complex may contribute to the suppressed IFN response via inactivation of TBK1/IRF3 by its DUB activity in MHV-A59 infected cells.Therefore, by tempering the ubiquitination of both TBK1 and IRF3, and subsequent phosphorylation of both, PLP2 would provide a favorable steric conformation for inter-molecular interaction between inactivated TBK1 and IRF3."
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"1108 npg therefore suggest that host cells lack the ability to produce type I IFN in response to MHV-A59 infection.Because ubiquitination plays an important role in the RIG-I-mediated IFN induction cascade [20] , and because PLpro domain 2 (PLP2) domain of MHV-A59 contains a conserved DUB motif [22] , we hypothesized that the DUB activity of PLP2 domain might block the IFNβ response during MHV-A59 infection."
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"This DUB activity may remove ubiquitin from innate immune signaling factors to suppress the induction of an antiviral state, and indeed was shown to reduce IFN signaling in biochemical experiments using PL2pro overexpression for several coronaviruses, including SARS-CoV (Matthews et al. 2014a; Li et al. 2016) and MERS-CoV (Chen et al. 2007; Clementz et al. 2010; Bailey-Elkin et al. 2014)."
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"We found that the DUBmut virus replicates similarly to the wild-type (WT) virus in cultured cells, but the DUBmut virus activates an IFN response at earlier times compared to the wild-type virus infection in macrophages, consistent with DUB activity negatively regulating the IFN response."
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"For example , the UPS was essential for coronavirus replication ( Raaben et al ., 2010 ) , whereas coronavirus papain-like proteases can act as DUBs that block type I IFN production ( Clementz et al ., 2010 ) ."
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"Both of these genes encode DUB that stimulate a type I IFN negative feedback mechanism by removing K63-linked poly ubiquitin chains on critical components of the antiviral signaling pathway such as RIG-I (Tao et al., 2020) and TBK1 (Cai et al., 2018)."
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"It is known that PLpro exhibits deubiquitinating (DUB) activity and antagonizes the induction of type-1 interferon (IFN), the interferon-stimulated gene 15 (ISG15) is the most overexpressed gene upon IFN stimulation and it’s involved in marking newly synthesised protein during an antiviral response."
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ZUP1 activates Interferon.
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ZUP1 activates Interferon. 5 / 5
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"For example, the DUB enzyme cylindromatosis (CYLD) was shown to directly bind RIG-I and mediate the removal of K63-ub and limit IFN induction [45]."
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"Here we characterized the DUB and IFN antagonism activities of the PLP domains of human coronavirus NL63 and severe acute respiratory syndrome (SARS) coronavirus to determine if DUB activity mediates interferon antagonism."
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"For instance, above-mentioned studies found the distantly related HCoV-NL63 and SARS-CoV to be similar in essential features such as protease-independent, DUB-mediated IFN antagonism, while the MERS-CoV that is much closer related to SARS-CoV only inhibits IFN induction when the protease function is intact (e.g., [34, 37])."
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"The blocking of induction of IFN by DUB activity was also confirmed for MERS-CoV, but in contrast to SARS-CoV, this inhibition is not independent of PLP’s protease activity [40, 41]."
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"We further 223 investigated the differences in the interferon response generated in response to WT versus 224 DUBmut virus in our companion study (Volk et al., submitted) , which further supports a role for 225 DUB activity in modulating the interferon response in macrophages.The structure-guided approach used to generate the DUBmut virus allowed for substitution."
| DOI
Mutated ZUP1 activates Interferon. 2 / 2
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"We engineered a recombinant murine coronavirus to express the DUB mutant and showed that the DUB mutant virus activated an earlier type I interferon response in macrophages and exhibited reduced pathogenesis in mice."
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"We engineered a recombinant murine coronavirus to express the DUB mutant and showed that the DUB mutant virus activated an earlier type I interferon response in macrophages and exhibited reduced replication in mice."
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ZUP1 affects Ubiquitin
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ZUP1 binds Ubiquitin.
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"Pull-down experiments in lysate using Ub-, SUMO2-, or UFM1 conjugated agarose revealed that FLAG-ZUFSP and FLAG-ZUFSP (298-578) interacted with Ub-agarose, but not with UFM1- or SUMO2-agarose, suggesting that ZUFSP binds preferentially to Ub."
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"20 Thus, probes containing short Ub peptides may not recapitulate the interaction between DUB and full length Ub."
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"Interestingly, while Ub and ISG15 bound to CCHFV OTU in similar orientations (Fig. 7A and B), the β-grasp domains of these substrates were rotated ~ 75° with respect to the orientation that Ub binds to a representative eukaryotic OTU DUB from yeast, yOTU1 (Fig. 7A)."
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"This closely parallels the use of Ubal to obtain Ub-bound DUB structures, prior to the development of DUB ABPs."
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"Binding of Ub to the DUB would result in fluorescence, and conversely, no fluorescence would occur in the presence of an inhibitor (Ott et al., 2017)."
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Ubiquitin binds ZUP1 and S2. 1 / 1
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"The SARS virus DUB, PLpro, cleaves K48poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of Ub S2 by utilizing a central Phe residue among other hydrophobic residues 42 ."
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ZUP1 inhibits Ubiquitin.
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ZUP1 inhibits Ubiquitin. 3 / 3
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"USP44, USP17L2/DUB3, USP11, ZUFSP and POH1 loss promotes the excessive spreading of Ub at DSBs and concomitant excessive accumulation of 53BP1 [57–65]."
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"In addition , the ubiquitin-proteasome pathway ( UPP ) regulates p53 stability and is modulated by DUBs that can eliminate ubiquitin from p53 ."
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"A20 is an OTU domain DUB that inhibits NF-kB upstream by removing ubiquitin from TRAF6 and RIP1, two signaling molecules of the NF-kB pathway."
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ZUP1 inhibits mutated Ubiquitin. 1 / 1
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"Mutation of the ubiquitin-interacting residues of EAV PLP2 had no evident effect on protease activity but significantly reduced DUB activity in overexpression studies."
24512893
ZUP1 activates Ubiquitin.
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ZUP1 activates Ubiquitin. 2 / 2
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"Also as expected, CCHFV-OTU is inhibited by specific inhibitors of DUB enzymes corresponding to ubiquitin and ISG15 derivates coupled to aldehyde or vinyl sulfone [15À18]."
| PMC
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"DUBs activate ubiquitin prior to conjugation , as well as remove it from the ubiquitinated proteins ( 1 ) ."
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ZUP1 decreases the amount of Ubiquitin.
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ZUP1 decreases the amount of Ubiquitin. 1 / 1
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"Similarly, as one of Coronavirus, it was reported that IBV-encoded PLP-TM functions as a DUB enzyme, which significant reduced the levels of ubiquitin (Ub)-, K48-, and K63-conjugated proteins in the early stage of viral infection [32]."
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Ubiquitin affects ZUP1
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Ubiquitin binds ZUP1.
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"Pull-down experiments in lysate using Ub-, SUMO2-, or UFM1 conjugated agarose revealed that FLAG-ZUFSP and FLAG-ZUFSP (298-578) interacted with Ub-agarose, but not with UFM1- or SUMO2-agarose, suggesting that ZUFSP binds preferentially to Ub."
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"20 Thus, probes containing short Ub peptides may not recapitulate the interaction between DUB and full length Ub."
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"Interestingly, while Ub and ISG15 bound to CCHFV OTU in similar orientations (Fig. 7A and B), the β-grasp domains of these substrates were rotated ~ 75° with respect to the orientation that Ub binds to a representative eukaryotic OTU DUB from yeast, yOTU1 (Fig. 7A)."
28625850
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"This closely parallels the use of Ubal to obtain Ub-bound DUB structures, prior to the development of DUB ABPs."
28196299
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"Binding of Ub to the DUB would result in fluorescence, and conversely, no fluorescence would occur in the presence of an inhibitor (Ott et al., 2017)."
30851297
Ubiquitin binds ZUP1 and S2. 1 / 1
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"The SARS virus DUB, PLpro, cleaves K48poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of Ub S2 by utilizing a central Phe residue among other hydrophobic residues 42 ."
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Ubiquitin inhibits ZUP1.
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Ubiquitin inhibits ZUP1. 5 / 5
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"The ubiquitin variant CC.4 binds to the OTU domain with high affinity and inhibits CCHFV DUB activity [27]."
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"Slopes of linear portions of fluorescent signal formation were used to determine the velocity of substrate cleavage in the presence and absence of ubiquitin variant CC.4 (CC.4) which has been shown previously to inhibit DUB activity of CCHFV isolated OTU-domain [27]."
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"DUB activity of both full length protein and OTU domain is inhibited by ubiquitin variant CC.4."
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"(C) Ubiquitin variant CC.4 inhibits DUB activity of both full length protein and OTU domain to a similar extent as illustrated by the 50% inhibitory concentrations (IC50)."
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"This variation is stated to be advantageous where for example; the DUB to be assayed is inhibited by ubiquitin dimmers [85] ."
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Ubiquitin activates ZUP1.
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Ubiquitin activates ZUP1. 2 / 2
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"For CCHFV, it was recently shown that the stable occupancy of the CCHFV-encoded DUB with a Ub variant, blocking OTU DUB activity, blocked viral infection in addition to enhancing host antiviral responses [205]."
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"New diUb-VME probes were developed containing two ubiquitin moieties conjugated by one of the seven possible linkage types, thereby allowing the determination of DUB’s linkage specificity (Mulder et al. 2014)."
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ZUP1 affects SIRT2
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ZUP1 increases the amount of SIRT2.
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ZUP1 increases the amount of SIRT2. 7 / 7
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"We also found that DUb upregulated SIRT2 expression in DUb-treated HCT116 and LoVo cells and CRC tissues treated with DUb."
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"(G) The results of immunohistochemical staining showed that DUb markedly increased the protein expression of SIRT2 in the CT26 xenograft tumors and patient-derived xenograft (PDX) tumors (n = 3)."
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"Furthermore, the results of IHC staining against SIRT2 antibodies shows that SIRT2 expression in the DUb-treated xenograft tumor is significantly increased as compared with control.Given that DUb upregulated SIRT2 expression, we speculated that DUb inhibited CRC growth by upregulating SIRT2."
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"We firstly found that DUb upregulated the SIRT2 expression in LoVo cells, but DUb did not affect SIRT2 expression after SIRT2 was silenced (Figure 6A)."
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"(F) The results of western blotting showed that DUb markedly increased the protein expression of SIRT2 in the CT26 xenograft tumors and patient-derived xenograft (PDX) tumors (n = 3)."
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"DUb significantly induced mRNA expression of SIRT2 in HCT116 (B) and LoVo cells (C)."
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"*p < 0.05; **p < 0.01; ***p < 0.001.FIGURE 5: DUb increases the expression of SIRT2."
35177983
ZUP1 inhibits SIRT2.
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ZUP1 inhibits SIRT2. 4 / 4
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"Furthermore, the results of IHC staining against SIRT2 antibodies shows that SIRT2 expression in the DUb-treated xenograft tumor is significantly increased as compared with control.Given that DUb upregulated SIRT2 expression, we speculated that DUb inhibited CRC growth by upregulating SIRT2."
35177983
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"Moreover, DUb inhibited CRC progression by upregulating SIRT2."
35177983
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"In the present study, we reported that DUb inhibited CRC growth by upregulating SIRT2."
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"It was further demonstrated that DUb inhibited LoVo cell proliferation, migration and invasion by upregulating SIRT2."
35177983
ZUP1 decreases the amount of SIRT2.
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ZUP1 decreases the amount of SIRT2. 1 / 1
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"In this study, we report an important finding that DUb, a coenzyme Q10 analog, can potently suppress CRC cell proliferation, migration and invasion by up-regulating SIRT2 expression."
35177983
Protease affects ZUP1
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Protease deubiquitinates ZUP1.
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Protease deubiquitinates ZUP1. 6 / 6
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"Analysis of enzymatic activity and structural studies revealed that SARS-CoV PLpro and HCoV-NL63 PLP2 function as both proteases and deubiquitinating (DUB) enzymes [14], [32]–[35]."
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"One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB) activity, and antagonizes the induction of type I interferon (IFN)."
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"Coronavirus papain-like proteases (PLPs) can act as proteases that process virus-encoded large replicase polyproteins and also as deubiquitinating (DUB) enzymes."
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"The papain-like protease of avian infectious bronchitis virus has deubiquitinating activity.Coronavirus papain-like proteases (PLPs) can act as proteases that process virus-encoded large replicase polyproteins and also as deubiquitinating (DUB) enzymes."
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"Analysis of enzymatic activity and structural studies revealed that SARS-CoV PLpro and HCoV-NL63 PLP2 function as both proteases and deubiquitinating (DUB) enzymes [14, [32] [33] [34] [35] ."
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"Abstract Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection."
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Protease activates ZUP1.
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Protease activates ZUP1. 5 / 5
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"Further studies are needed to determine if these inhibitors can be developed into clinically useful antiviral agents.Analysis of SARS-CoV papain-like protease led to the surprising discovery that this protease is also a viral deubiquitinating (DUB) enzyme."
| PMC
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"These findings lead us to an intriguing alternative hypothesis , that protease inhibitors reduce the levels / activity of the DUBs that target these viral oncoproteins , thereby causing increased ubiquitination of E6 and E7 , and consequently increased degradation ."
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"Furthermore , addition of a protease inhibitor that blocks both protease and DUB activity [ 52 ] failed to abrogate the PLP inhibition on activation of IRF-3 dependent promoters [ 14 ] ."
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"For the distantly related arterivirus EAV, infection with a mutant lacking a similar papain-like protease-driven DUB activity resulted in an increased innate immune response after infection, indicating that the viral DUB activity indeed has a function in suppression of innate immune response during infection (van Kasteren et al. 2013)."
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"Further studies are needed to determine if these inhibitors can be developed into clinically useful antiviral agents.Analysis of SARS-CoV papain-like protease led to the surprising discovery that this protease is also a viral deubiquitinating (DUB) enzyme."
| PMC
PLP2 affects ZUP1
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PLP2 inhibits ZUP1.
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PLP2 inhibits ZUP1. 7 / 7
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"We found that mutating 42 the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease 43 activity ."
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"For example, the mutations D91R and T88R largely blocked the PLP2 activity and E90R partially blocked the DUB activity (Figure 4)."
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"We found that mutating the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease activity."
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"We found that mutating the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease activity ."
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"We found that mutating 42 the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease 43 activity."
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"We found that mutating the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease activity ."
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"We found that mutating the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease activity."
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PLP2 activates ZUP1.
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PLP2 activates ZUP1. 1 / 1
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"This result suggests that this inhibitory effect of PLP2 is partially dependent on its DUB activity ."
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ZUP1 affects DNA Damage
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ZUP1 inhibits DNA Damage.
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ZUP1 inhibits DNA Damage. 5 / 5
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"Scale bar, 10 μm. See also Figure S6.Figure 7: ZUFSP Prevents Spontaneous DNA Damage and Promotes Cellular Survival in Response Exogenous DNA Damage (A) U2-OS cells were transfected with control (siCTRL) or ZUFSP (siZUFSP) siRNAs for 72 hr and then lysed and analyzed by immunoblotting with the indicated antibodies."
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"While WT ZUFSP effectively rescued the DNA damage phenotype in ZUFSP depleted cells, the C360S mutant was unable to, suggesting that the DUB activity of ZUFSP is required to prevent spontaneous DNA damage in cells (Figure 7F)."
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"ZUFSP Prevents Spontaneous DNA Damage and Promotes Cellular Survival in Response Exogenous DNA Damage (A) U2-OS cells were transfected with control (siCTRL) or ZUFSP (siZUFSP) siRNAs for 72 hr and then lysed and analyzed by immunoblotting with the indicated antibodies."
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"While WT ZUFSP effectively rescued the DNA damage phenotype in ZUFSP depleted cells, the C360S mutant was unable to, suggesting that the DUB activity of ZUFSP is required to prevent spontaneous DNA damage in cells (XREF_FIG F)."
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"Furthermore, loss of ZUFSP in human cancer cells led to increased endogenous DNA damage in these cells, and we could further show that this endogenous DNA damage originates in S-phase."
29576527
ZUP1 activates DNA Damage.
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ZUP1 activates DNA Damage. 2 / 2
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"While WT ZUFSP effectively rescued the DNA damage phenotype in ZUFSP depleted cells, the C360S mutant was unable to, suggesting that the DUB activity of ZUFSP is required to prevent spontaneous DNA damage in cells (XREF_FIG F)."
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"While WT ZUFSP effectively rescued the DNA damage phenotype in ZUFSP depleted cells, the C360S mutant was unable to, suggesting that the DUB activity of ZUFSP is required to prevent spontaneous DNA damage in cells (Figure 7F)."
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ZUP1 inhibits cell population proliferation. 6 / 6
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"(A) After HCT116 and LoVo cells were treated with DUb or DMSO for 96 h, DUb suppressed the proliferation of HCT116 and LoVo cells (n = 12)."
35177983
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"It was further demonstrated that DUb inhibited LoVo cell proliferation, migration and invasion by upregulating SIRT2."
35177983
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"We demonstrated that DUb significantly reduced the proliferation of HCT116 and LoVo cells in a dose-dependent manner (Figure 3A)."
35177983
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"We found that DUb inhibits CRC cell proliferation through up-regulating SIRT2 in CRC cells."
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"Our findings provided direct evidence that DUb has the potential to be an effective therapeutic agent for CRC.To explore how DUb inhibits CRC cell proliferation, qRT-PCR analysis was performed to determine cancer-related genes using DUb-treated CRC cells."
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"In addition, DUb significantly decreased cell proliferation in tumor tissues as detected by immunohistochemical staining for Ki67 (Figure 1C), which can be used as an index of cell proliferation."
35177983
ZUP1 affects IFNB1
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ZUP1 inhibits IFNB1.
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ZUP1 inhibits IFNB1. 4 / 4
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"We previously found that the DUB activity of MERS-CoV PLpro suppresses IFN-β promoter activity upon activation of cellular innate immune signaling [9]."
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"These reports collectively indicate that coronaviruses express viral proteins with DUB activity to reduce IFN-β, which contributes to rapid viral growth and thus SARSassociated immunopathology."
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"For example, herpes simplex virus 1 encodes the largest tegument protein, UL36, which acts as a DUB to remove ubiquitin chains from TNF receptor associated factor 3 (TRAF3) and consequently inhibits IFN-β signaling [89•]."
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"Our results comparing various 3C pro mutants suggest that the DUB activity of 3C pro enables it to block induction of the IFN-β promoter and the Fig. 4 ."
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Mutated ZUP1 inhibits IFNB1. 1 / 1
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"This was supported by a study by Bailey-Elkin et al., in which they obtained the crystal structure of PLpro-Ub complex and showed that WT MERS-CoV PLpro, but not the DUB mutant PLpro, suppresses IFN-β promotor activity [33]."
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ZUP1 activates IFNB1.
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ZUP1 activates IFNB1. 1 / 1
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"Cell-based assays showed that UbV.ME.4 efficiently suppressed the DUB-induced activation of IFN-β promoter, thereby providing efficient blockade of viral replication and reducing MERS-CoV progeny titer by ~10,000-fold (W. Zhang, Bailey-Elkin, et al., 2017)."
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ZUP1 affects DDX58
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ZUP1 ubiquitinates DDX58.
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ZUP1 ubiquitinates DDX58. 3 / 3
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"Studies have shown that DUB activity of nsp2(N) from EAV can block RIG-I ubiquitination in a catalytic dependent manner (van Kasteren et al., 2012)."
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"Studies have shown that DUB activity of nsp2 (N) from EAV can block RIG-I ubiquitination in a catalytic dependent manner (48) ."
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"The DUB activity of Lb was further confirmed through observation of the inhibitory effects of Lb on ubiquitination of RIG-I, TRAF3, TRAF6, and TBK1, which eventually prevents activation of the type I IFN pathway."
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ZUP1 deubiquitinates DDX58.
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ZUP1 deubiquitinates DDX58. 2 / 2
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"USP3 is also a DUB that deubiquitinates K63-polyUb chain of both RIG-I and MDA5 and suppresses IFN-β activation [25]."
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"However, nairoviruses, like arterviruses, encode DUB enzymes that deubiquitinate RIG-I to prevent innate immune signaling activation (van Kasteren et al., 2012), suggesting that during nairovirus infection/replication a PAMP, likely a viral transcription product, is produced that can activate RIG-I."
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ZUP1 inhibits DDX58.
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ZUP1 inhibits DDX58. 1 / 1
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"For example, the 3C protein of enterovirus 71 (EV71), a member of the Picornaviridae family that causes hand, foot and mouth disease, and occasionally severe central nervous system diseases, downregulates the host microRNA miR-526a to increase the expression of the cellular DUB enzyme CYLD, thus inhibiting the activation of RIG-I 74 ."
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ZUP1 affects CRC
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ZUP1 inhibits CRC. 6 / 6
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"In the present study, we reported that DUb inhibited CRC growth by upregulating SIRT2."
35177983
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"Moreover, DUb inhibited CRC progression by upregulating SIRT2."
35177983
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"These data suggest that DUb inhibits CRC growth by impeding tumor cell proliferation.Given that DUb suppresses mouse-derived CRC growth, we speculated that DUb can also inhibit human-derived CRC growth by attenuating tumor cell proliferation."
35177983
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"Herein, we found that DUb significantly inhibited CRC growth in the patient-derived xenograft (PDX) and CT26 xenograft models."
35177983
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"These results show that DUb reduces CRC growth by suppressing tumor cell proliferation in vivo.To explore the effect of DUb on CRC cell proliferation, HCT116 and LoVo cells were treated with different concentrations of DUb for 96 h, and the cell viability was detected by the MTT assay."
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"Furthermore, the results of IHC staining against SIRT2 antibodies shows that SIRT2 expression in the DUb-treated xenograft tumor is significantly increased as compared with control.Given that DUb upregulated SIRT2 expression, we speculated that DUb inhibited CRC growth by upregulating SIRT2."
35177983
ZUP1 affects CRC growth
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ZUP1 inhibits CRC growth. 6 / 6
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"Therefore, DUb may inhibit CRC growth by affecting the metabolism of colorectal cancer.Taken together, as an important finding of the current study, DUb is determined to suppress CRC growth in xenograft mouse models with CRC CT26 cells and human CRC tissues."
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"Our results show that DUb markedly suppresses CRC growth in xenograft mouse models with colorectal carcinoma CT26 cells and human-derived xenograft tumor."
35177983
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"DUb was found to significantly attenuate CRC growth (Figure 1A) and weight (Figure 1B)."
35177983
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"Scale bar = 50 µm in C. **p < 0.01.FIGURE 2: DUb inhibits the CRC growth in the patient-derived xenograft (PDX) tumor models."
35177983
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"These results shows that DUb reduces the migratory and invasive abilities of CRC cell.To determine the mechanism of DUb inhibiting CRC growth, a qRT-PCR array was performed."
35177983
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"Our results in this study demonstrates that DUb may be the potential agent for the treatment of CRC through upregulating SIRT2.FIGURE 1: DUb inhibits CRC growth in CT26 xenograft tumor models."
35177983
CSH1 affects ZUP1
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CSH1 deubiquitinates ZUP1.
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CSH1 deubiquitinates ZUP1 on proline. 2 / 2
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"In addition, PL pro exhibits deubiquitinating (DUB) activity and antagonizes the induction of type-1 interferon (IFN)."
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"Like its SARS-CoV counterpart, the MERS-CoV PL pro also has deubiquitinating (DUB) and deISGylating activities in vivo as well as in vitro (Yang et al., 2013; Mielech et al., 2014; Lei et al., 2014; Baez-Santos et al., 2014b) ."
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CSH1 deubiquitinates ZUP1. 2 / 2
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"Herbs and natural compounds able to inhibit the PL PRO 's deubiquitinating (DUB) and deISGylating activities would also increase their effectiveness against the CoV 63,48,90 ."
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"It is known that PL pro exhibits deubiquitinating (DUB) activity and antagonizes the induction of type-1 interferon (IFN), the interferon-stimulated gene 15 (ISG15) is the most overexpressed gene upon IFN stimulation and it's involved in marking newly synthesised protein during an antiviral response."
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CSH1 inhibits ZUP1.
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CSH1 inhibits ZUP1. 2 / 2
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"This also resulted in the strongest inhibition by PL pro , providing a maximum window to assess the effects on IFN-␤ promoter inhibition by the PL pro mutants with specifically inactivated DUB activity."
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"23 In previous work, we determined the crystal structure of MERS-CoV PL pro in complex with ubiquitin, 24 facilitating the design of PL pro mutations that impair DUB activity without affecting viral polyprotein 25 cleavage."
| DOI
ZUP1 affects pathogenesis
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ZUP1 activates pathogenesis.
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ZUP1 activates pathogenesis. 4 / 4
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"Collectively, this 173 demonstrates that CoV PL pro 's DUB activity enhances virulence in an animal model and that selective 174 removal of this activity could be a basis for the design of MLV vaccines."
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"In summary, coronaviruses PLPs are multifunctional enzymes with cysteine protease, DUB and deISGylating activities that contribute significantly to infection pathogenesis."
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"This study provides the first 35 direct evidence that the DUB activity of a coronaviral protease contributes to innate immune evasion 36 and can profoundly enhance virulence in an animal model."
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"In summary, this indicates that the DUB activity of nsp3 is a major contributor to the pathogenesis of coronavirus infections."
31635238
ZUP1 inhibits pathogenesis.
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ZUP1 inhibits pathogenesis. 1 / 1
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"Pathogenesis and lethality can thus be reduced by removal of the DUB 649 activity, resulting in earlier, better-regulated and therefore likely more effective innate immune 650 response that helps to clear the virus and decreases pathogenicity, despite the initial viral replication 651 being similar to that seen in wt virus infections."
| DOI
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"This strategy is not unique to viruses because the bacterial virulence factor YopJ also functions as a DUB that inhibits TRAFsmediated innate immune response [35] ."
18957937
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"To assess whether DUB-negative mutants indeed induce a stronger 374 innate immune response than wt rMERS-CoV, mRNA levels of IFN-β, IFIT2, and viperin in infected 375 cells were measured by real-time RT-qPCR."
| DOI
reach
"Importantly, we have recently been able to show that the DUB activity of EAV PLP2 inhibits the innate immune response in infected cells, via the structure-based design of a viable mutant virus lacking this activity (van Kasteren et al., 2013)."
25975520
ZUP1 activates innate immune response.
| 2
reach
"Overexpression studies revealed that viral protease/DUB activity can modulate or block activation of the innate immune response pathway."
24512893
reach
"• Coronaviruses and arteriviruses encode papain-like protease domains that process the replicase polyprotein and are required for viral replication• Many viral papain-like proteases are multifunctional and have protease, deubiquitinating and deISGylating activity• Structural and enzymatic studies revealed the multifunctional nature of coronavirus and arterivirus papain-like proteases• Viral DUB and deISGylating activity is proposed to modulate the innate immune response• An arterivirus papain-like protease has been shown to modulate the innate immune response to viral infection (49) ."
24512893
ZUP1 affects SGCG
| 5
ZUP1 inhibits SGCG.
| 4
ZUP1 inhibits SGCG. 4 / 4
| 4
reach
"For example, viral DUB activity of CCHFV OTU and equine arteritis virus OTU suppresses type I IFN signaling during infection (7) (8) (9) , whereas the turnip yellow mosaic virus DUB counters Ub-mediated proteasomal degradation of its polymerase (17) ."
31337717
reach
"One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB) activity, and antagonizes the induction of type I interferon (IFN)."
20181693
reach
"In particular, the DUB and deISGylating activities encoded by nsp3 suppress the induction and signaling of type I interferons.The functional implication of PTMs on many coronavirus proteins has not been fully characterized, and their biological significance requires further investigations combining reverse genetics and suitable in vivo models."
32201497
reach
"For example, viral DUB activity of CCHFV OTU and equine arteritis virus OTU suppresses type I IFN signaling during infection (7–9), whereas the turnip yellow mosaic virus DUB counters Ub-mediated proteasomal degradation of its polymerase (17)."
31337717
ZUP1 activates SGCG.
| 1
Mutated ZUP1 activates SGCG. 1 / 1
| 1
reach
"We engineered a recombinant murine coronavirus to express the DUB mutant and showed 44 that the DUB mutant virus activated an earlier type I interferon response in macrophages and 45 exhibited reduced pathogenesis in mice."
| DOI
ZUP1 affects Proteasome
| 5
ZUP1 binds Proteasome.
| 3
reach
"The ubiquitin-specific protease USP14 is a UBQ-trimming, proteasome-bound DUB that frees and recycles UBQ before substrate protein degradation by the UPS [33]."
| PMC
reach
"In mammalian cells, a greater number of polypeptides were labeled, most of which were DUBs, including a DUB that associates with the mammalian 26S proteasome, novel protein USP14, a mammalian homolog of yeast Ubp6p [81] ."
26077642
Proteasome binds ZUP1 and cysteine. 1 / 1
| 1
reach
"The first of these ubiquitin ABPs was ubiquitin-nitrile, which allowed the labeling of a proteasome-bound cysteine dependent DUB [36]."
25461387
ZUP1 inhibits Proteasome.
| 1
ZUP1 inhibits Proteasome. 1 / 1
| 1
reach
"Conversely, MuRF2 ubiquitination could be enhancing a de-ubiquitinase (DUB) that prevents proteasome-mediated degradation by this unidentified E3(s)."
26242235
ZUP1 activates Proteasome.
| 1
ZUP1 activates Proteasome. 1 / 1
| 1
reach
"Interestingly, the CCHFV OTU protease comprises a domain on the viral polymerase, and targeting it with a UbV may not only suppress viral pathogenicity but RNA replication as well, since it has been found that viral OTU DUB activity can suppress proteasome-dependent viral polymerase degradation [43]."
28542609
Proteasome affects ZUP1
| 5
Proteasome binds ZUP1.
| 3
reach
"The ubiquitin-specific protease USP14 is a UBQ-trimming, proteasome-bound DUB that frees and recycles UBQ before substrate protein degradation by the UPS [33]."
| PMC
reach
"In mammalian cells, a greater number of polypeptides were labeled, most of which were DUBs, including a DUB that associates with the mammalian 26S proteasome, novel protein USP14, a mammalian homolog of yeast Ubp6p [81] ."
26077642
Proteasome binds ZUP1 and cysteine. 1 / 1
| 1
reach
"The first of these ubiquitin ABPs was ubiquitin-nitrile, which allowed the labeling of a proteasome-bound cysteine dependent DUB [36]."
25461387
Proteasome deubiquitinates ZUP1.
| 2
Proteasome deubiquitinates ZUP1. 2 / 2
| 2
reach
"ISG15 conjugation may also help direct modified proteins to the proteasome, because the proteasome-associated deubiquitinating enzyme (DUB), USP14, can recognize ISG15-modified substrates, or it may function to attract components of the ubiquitin conjugation machinery.ISG15 plays a role in resistance to Ebola virus (also VSV and rabies virus) by blocking the activity of Nedd4 via ISGylation (reviewed in Sadler and Williams, 2008)."
19527883
reach
"Proteasomes function under tonic inhibitory conditions, possibly via the ubiquitin chain-trimming function of USP14, a proteasome-associated deubiquitinating enzyme (DUB)."
26041011
PR-619 affects ZUP1
| 5
PR-619 inhibits ZUP1. 5 / 5
| 5
eidos
"Notably , inhibition of DUB activities by PR-619 in the cell lysate-based experiment is more pronounced than that in the cell-based experiment ."
30240200
eidos
"As expected , PR-619 strongly inhibited the activities of almost all DUBs tested , and SJB3-019A inhibited most of USPs but not OTUs , and its inhibitory efficiency was different for individual USPs ( Figure 4B and Table S3 ) ."
| PMC
eidos
"For example , one study used ABPs to demonstrate the selectivity of P22077 for USP7 in cells , in contrast to PR-619 , which inhibited a broad range of DUBs 239 ."
28959952
eidos
"Treatment of HeLa cells with high concentrations of PR-619 ( 50 muM ) led to reduced intensity in many labeled DUB bands , indicating intracellular inhibition of DUB activity by PR-619 ( Figure 6 ) ."
30240200
eidos
"The recent study on the DUB selectivity of literature inhibitors by MALDI-TOF MS agreed that PR-619 strongly inhibits all DUBs tested ( covering USP / UCH / MJD / OTU families ) at 5 muM ."
26852935
Mutation affects ZUP1
| 5
Mutation inhibits ZUP1. 5 / 5
| 5
eidos
"It is interesting to note that Ile83Ala / Leu86Ala mutations targeted the SAF-A / B , Acinus , and PIAS ( SAP ) domain within Lpro [ 235 ] , and while these mutations selectively abrogate DUB activity [ 240 ] and delay nuclear translocation [ 235 ] , they do not appear to target the likely Ub-binding interface of Lpro , which has been demonstrated to be an effective means to inhibit the DUB activity of other vDUBs [ 162 ] , [ 199 ] ."
28625850
eidos
"Mutations that affect the mobility of the loop and prevent the close conformation resulted in a loss of DUB activity while conserving the protease function [ 27 ] ."
30650571
eidos
"In the case of TYMV , these two activities can be uncoupled by mutations that selectively suppress the DUB activity without altering PRO ( Jupin et al ., 2017 ) ."
29868107
eidos
"This mutation , along with others , abrogated DUB activity yet permitted polyprotein cleavage at the nsp2-3 junction , thus providing an ideal system to directly assess whether PLpro DUB activity alone disrupts cellular signaling ."
28625850
eidos
"Interestingly , this residue ( equivalent of Glu168 in SARS PLpro ) seems to play an important role in Ub1 core recognition , and mutations can cause a significant loss of DUB activity ."
33531496
ZUP1 affects Neoplasms
| 1 3
ZUP1 inhibits Neoplasms.
| 2
ZUP1 inhibits Neoplasms. 2 / 2
| 2
reach
"Our results in this study demonstrates that DUb may be the potential agent for the treatment of CRC through upregulating SIRT2.FIGURE 1: DUb inhibits CRC growth in CT26 xenograft tumor models."
35177983
reach
"Compared with DMSO group, DUb significantly decreased tumor volume (Figure 2A) of human-derived xenograft tumor."
35177983
ZUP1 activates Neoplasms.
| 1 1
ZUP1 activates Neoplasms. 2 / 2
| 1 1
reach
"A benign tumor syndrome of hair follicles known as cylindromatosis is caused by the mutation of CYLD, a USPfamily DUB named after the disease it causes."
19571111
eidos
"Most DUBs will promote the occurrence of tumors , but a small number of DUBs play the opposite role ."
33498168
ZUP1 affects NFkappaB
| 1 3
ZUP1 inhibits NFkappaB.
| 3
ZUP1 inhibits NFkappaB. 3 / 3
| 3
reach
"A20 is an OTU domain DUB that inhibits NF-kB upstream by removing ubiquitin from TRAF6 and RIP1, two signaling molecules of the NF-kB pathway."
19527883
reach
"The YopJ DUB inhibits NF-kB and mitogen-activated protein kinase (MAPK) pathways, a function ascribed previously to its somewhat promiscuous deubiquitination of critical cellular proteins, such as TRAF2, TRAF6, and IkB."
17145306
reach
"Conversely, CYLD, a human DUB that negatively regulates the NF-kB pathway, is specific for K63-based Ub chains."
24854014
ZUP1 activates NFkappaB.
| 1
ZUP1 activates NFkappaB. 1 / 1
| 1
eidos
"Investigations into 19S proteasome deubiquitinates showed that inhibition of these DUBs prevents the breakdown of IkappaBalpha and leads to the inactivation of NF-kappaB , which suppresses cardiac remodeling ( Hu et al ., 2018 ) ."
33584340
PLpro affects ZUP1
| 4
PLpro deubiquitinates ZUP1. 4 / 4
| 4
reach
"In addition, PLpro exhibits deubiquitinating (DUB) activity and antagonizes the induction of type-1 interferon (IFN)."
28112000
reach
"Abstract Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection."
24503068
reach
"It is known that PLpro exhibits deubiquitinating (DUB) activity and antagonizes the induction of type-1 interferon (IFN), the interferon-stimulated gene 15 (ISG15) is the most overexpressed gene upon IFN stimulation and it’s involved in marking newly synthesised protein during an antiviral response."
34515981
reach
"6, 7 On the basis of this similarity in molecular architecture and the predicted specificity of PLpro for cleavage after a diglycine residue, Sulea and co-workers predicted that PLpro has deubiquitinating (DUB) activity.To test this prediction we used our experimentally determined catalytic core domain in an in vitro assay for deubiquitination."
17037501
FLCN affects ZUP1
| 4
FLCN activates ZUP1.
| 3
Mutated FLCN activates ZUP1. 2 / 2
| 2
reach
"Birt–Hogg–Dubé (BHD) syndrome is caused by mutation of the folliculin (FLCN) gene that encodes the tumor suppressor protein folliculin [1]."
36324339
reach
"Inactive mutation of FLCN causes Birt–Hogg–Dubé syndrome (BHD, OMIM#135150)."
25160977
FLCN activates ZUP1. 1 / 1
| 1
reach
"Birt–Hogg–Dubé (BHD) syndrome is caused by mutation of the folliculin (FLCN) gene that encodes the tumor suppressor protein folliculin [1]."
36324339
FLCN inhibits ZUP1.
| 1
FLCN inhibits ZUP1. 1 / 1
| 1
reach
"Loss of the tumor suppressor folliculin (FLCN) leads to Birt–Hogg–Dubé (BHD) syndrome, a condition characterized by cutaneous fibrofolliculomas, spontaneous pneumothorax and pulmonary cyst development, as well as renal cell carcinoma ."
34381247
Valproic acid affects ZUP1
3 |
Valproic acid decreases the amount of ZUP1.
2 |
Valproic acid decreases the amount of ZUP1. 2 / 2
2 |
ctd
No evidence text available
28001369
ctd
No evidence text available
23179753
Valproic acid demethylates ZUP1.
1 |
Valproic acid demethylates ZUP1. 1 / 1
1 |
ctd
No evidence text available
29154799
Ubiquitin-binding surface PLP2 affects ZUP1
| 3
Ubiquitin-binding surface PLP2 inhibits ZUP1. 3 / 3
| 3
eidos
"Here , we used X-ray structure-21 guided mutagenesis and functional studies to identify amino acid substitutions within the 22 ubiquitin-binding surface of PLP2 that reduced DUB activity without affecting polyprotein 23 processing activity ."
| DOI
eidos
"Here , we used X-ray structure-guided mutagenesis and functional studies to identify amino acid substitutions within the ubiquitin-binding surface of PLP2 that reduced DUB activity without affecting polyprotein processing activity ."
| DOI
eidos
"Here , we used X-ray structure-guided mutagenesis and functional studies to identify amino acid substitutions within the ubiquitin-binding surface of PLP2 that reduced DUB activity without affecting polyprotein processing activity ."
32188728
MonoUb affects ZUP1
| 3
ZUP1 binds monoUb. 3 / 3
| 3
reach
"Lys48-linked Ub chains are highly abundant in cells (Kirkpatrick et al., 2006), and their conjugation to other proteins targets them for proteasomal degradation (Chau et al., 1989), but the molecular basis for DUB recognition of Lys48-linked Ub chains remains unclear.Ub-based chemical probes have been widely used to profile DUB activities and to stabilize monoUb-bound DUB complexes for structure determination (Ekkebus et al., 2013, Hemelaar et al., 2004)."
27203180
reach
"Lys48-linked Ub chains are highly abundant in cells (Kirkpatrick et al., 2006) , and their conjugation to other proteins targets them for proteasomal degradation (Chau et al., 1989) , but the molecular basis for DUB recognition of Lys48-linked Ub chains remains unclear.Ub-based chemical probes have been widely used to profile DUB activities and to stabilize monoUb-bound DUB complexes for structure determination Hemelaar et al., 2004) ."
27203180
reach
"While the molecular basis for monoUb specificity for many human and viral DUBs was revealed in structures of monoUb-bound DUB complexes, the molecular basis of Ub chain linkage specificity is understood only for a handful of DUBs (Keusekotten et al., 2013, Mevissen et al., 2013, Sato et al., 2015)."
27203180
ZUP1 affects viral process
| 3
ZUP1 activates viral process.
| 2
ZUP1 activates viral process. 2 / 2
| 2
reach
"For CCHFV, it was recently shown that the stable occupancy of the CCHFV-encoded DUB with a Ub variant, blocking OTU DUB activity, blocked viral infection in addition to enhancing host antiviral responses [205]."
33925004
reach
"Specifically, PLPs use their DUB activity to interfere with the proteins that mediate the intracellular sensing and signaling of viral infection, therefore leading to a dysregulation of the immune pathways, such as the IRF3 and NF-kB pathways, that in turn, results in a decrease in the antiviral response."
32429099
ZUP1 inhibits viral process.
| 1
ZUP1 inhibits viral process. 1 / 1
| 1
reach
"Both Ub and ISG15 are important signaling elements of the host innate immune response against viral infection, which can be negatively regulated by viral DUB and deISGylating enzymes (Calistri et al., 2014)."
25554382
ZUP1 affects viral polymerase
| 3
ZUP1 activates viral polymerase. 3 / 3
| 3
reach
"We also reported that the TYMV papain-like cysteine PRO domain involved in the proteolytic processing of the viral replication precursor protein [29–31], also displays a DUB activity that was able to rescue the viral polymerase from degradation [32]."
29117247
reach
"Interestingly, the CCHFV OTU protease comprises a domain on the viral polymerase, and targeting it with a UbV may not only suppress viral pathogenicity but RNA replication as well, since it has been found that viral OTU DUB activity can suppress proteasome-dependent viral polymerase degradation [43]."
28542609
reach
"We also reported that the TYMV papain-like cysteine PRO domain involved in the proteolytic processing of the viral replication precursor protein [29] [30] [31] , also displays a DUB activity that was able to rescue the viral polymerase from degradation [32] ."
29117247
ZUP1 affects monoUb
| 3
ZUP1 binds monoUb. 3 / 3
| 3
reach
"Lys48-linked Ub chains are highly abundant in cells (Kirkpatrick et al., 2006), and their conjugation to other proteins targets them for proteasomal degradation (Chau et al., 1989), but the molecular basis for DUB recognition of Lys48-linked Ub chains remains unclear.Ub-based chemical probes have been widely used to profile DUB activities and to stabilize monoUb-bound DUB complexes for structure determination (Ekkebus et al., 2013, Hemelaar et al., 2004)."
27203180
reach
"Lys48-linked Ub chains are highly abundant in cells (Kirkpatrick et al., 2006) , and their conjugation to other proteins targets them for proteasomal degradation (Chau et al., 1989) , but the molecular basis for DUB recognition of Lys48-linked Ub chains remains unclear.Ub-based chemical probes have been widely used to profile DUB activities and to stabilize monoUb-bound DUB complexes for structure determination Hemelaar et al., 2004) ."
27203180
reach
"While the molecular basis for monoUb specificity for many human and viral DUBs was revealed in structures of monoUb-bound DUB complexes, the molecular basis of Ub chain linkage specificity is understood only for a handful of DUBs (Keusekotten et al., 2013, Mevissen et al., 2013, Sato et al., 2015)."
27203180
ZUP1 affects cell death
| 1 2
ZUP1 inhibits cell death.
| 1 1
ZUP1 inhibits cell death. 2 / 2
| 1 1
reach
"A report uncovered that the combination treatment of EDL-360 with DUb effectively suppressed glioma tumorigenesis by inducing cell death (Hosni-Ahmed et al., 2014)."
35177983
eidos
"Inhibition of GSH synthesis , in combination with DUB inhibition , led to an accumulation of polyubiquitinated proteins , induction of proteotoxic stress , and cell death ."
30799286
ZUP1 activates cell death.
| 1
ZUP1 activates cell death. 1 / 1
| 1
reach
"DUb was also found to induce PTP-dependent cell death in Clone-9 and MH1C1 cells (Devun et al., 2010)."
35177983
ZUP1 affects Ubiquitination
| 3
ZUP1 inhibits Ubiquitination. 3 / 3
| 3
eidos
"Ubiquitination is reversed by DUBs and disassembles polyubiquitin chains ."
32455657
eidos
"As mentioned above , the DUB do not just reverse ubiquitination , but they also have many diverse functions , such as protein trafficking , apoptosis , chromatin remodeling , DNA damage repair and cell cycle regulation , and are particularly involved in cell signaling related to cancers ( Antao et al. 2020 ) ."
33165832
eidos
"Deubiquitinating enzymes ( DUB ) can reverse ubiquitination by removing ubiquitin from the substrate ( 100 ) ."
33777739
ZUP1 affects SRGN
| 3
ZUP1 binds SRGN. 3 / 3
| 3
reach
"The final data collection and refinement statistics for the ZUFSP-Ub-Prg complex structure is shown in Table 1."
29576527
reach
"The final data collection and refinement statistics for the ZUFSP-Ub and Prg complex structure is shown in XREF_TABLE."
29576527
reach
"(H) Structural superposition of UFM1 onto the ZUFSP-Ub-Prg complex structure."
29576527
ZUP1 affects NF-B
| 3
ZUP1 inhibits NF-B. 3 / 3
| 3
reach
"Importantly, our data showed the DUB activity is responsible for the ability of Nsp11 to inhibit NF-B activation, revealing a novel mechanism evolved by PRRSV to disarm host innate immune responses."
26342881
reach
"As shown in Fig. 6A , the results showed that mutants with impaired DUB activity were attenuated for the ability to suppress NF-B activation."
26342881
reach
"DUB activity is essential for PRRSV Nsp11 to block NF-B activation."
26342881
ZUP1 affects Disease
| 1 2
ZUP1 activates Disease. 2 / 2
| 1 1
eidos
"The above examples describe pathological conditions that are caused by expression of heterologous DUBs or by mutations of endogenous DUBs , although many other disease states or cellular functions have been shown to be modulated by DUBs ."
19571111
reach
"The same enzyme preparations can be employed to identify novel polymerase and DUB inhibitors.The tick-born Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe human disease with high fatality rates."
32497085
Mutated ZUP1 activates Disease. 1 / 1
| 1
reach
"There are only a few DUB mutations that are currently known to cause disease, but it is very likely that more will be recognized in the future."
19571111
ZUP1 affects DNA replication
| 3
ZUP1 inhibits DNA replication. 3 / 3
| 3
reach
"Given that loss of ZUFSP in human cancer cells both causes endogenous DNA replication stress and sensitizes cells to further exogenous DNA damage, it will now be important to understand whether, and how, ZUFSP loss synergizes with defects in other DDR pathways."
29576527
reach
"Given that loss of ZUFSP in human cancer cells both causes endogenous DNA replication stress and sensitizes cells to further exogenous DNA damage, it will now be important to understand whether, and how, ZUFSP loss synergizes with defects in other DDR pathways.Requests for further information or reagents should be directed to the Lead Contact and corresponding author, Yogesh Kulathu (ykulathu@dundee.ac.uk)."
29576527
reach
"Given that loss of ZUFSP in human cancer cells both causes endogenous DNA replication stress and sensitizes cells to further exogenous DNA damage, it will now be important to understand whether, and how, ZUFSP loss synergizes with defects in other DDR pathways.Detailed methods are provided in the online version of this paper and include the following: We thank H. Walden, C. Arkinson, and members of the Kulathu lab for discussions and critical comments on the manuscript."
29576527
WDR48 affects ZUP1
| 3
WDR48 activates ZUP1. 3 / 3
| 3
reach
"WDR48 and WDR20 bind the DUBs relatively far from the catalytic cleft and stimulate DUB catalytic activity via allosteric mechanisms (Figure 1; Yin et al., 2015; Dharadhar et al., 2016; Li et al., 2016)."
29302259
reach
"WDR48 stimulates the activity of three DUBs, USP12, USP46 and USP1, a DUB which regulates the Fanconi anemia DNA damage pathway (Cohn et al., 2007, 2009; Faesen et al., 2011)."
29302259
reach
"WDR48 stimulates the activity of three DUBs, USP12, USP46 and USP1, a DUB which regulates the Fanconi anemia DNA damage pathway (Cohn et al., 2007 (Cohn et al., , 2009 Faesen et al., 2011) ."
29302259
WDR20 affects ZUP1
| 1 2
WDR20 activates ZUP1.
| 1 1
WDR20 activates ZUP1. 2 / 2
| 1 1
reach
"WDR48 and WDR20 bind the DUBs relatively far from the catalytic cleft and stimulate DUB catalytic activity via allosteric mechanisms (Figure 1; Yin et al., 2015; Dharadhar et al., 2016; Li et al., 2016)."
29302259
eidos
"The DUB can be further activated by WDR20 , which anchors at the base of BL1 but allosterically regulates the conformation of BL2 and the catalytic cleft ."
27373336
WDR20 binds ZUP1.
| 1
WDR20 binds ZUP1. 1 / 1
| 1
reach
"WDR20 also binds the DUB via the “top” face of its β-propeller but interacts with the bottom of the palm subdomain of USP12 to promote an optimal alignment of the catalytic cleft (Li et al., 2016)."
29302259
UCHL1 affects ZUP1
| 3
UCHL1 inhibits ZUP1.
| 2
UCHL1 inhibits ZUP1. 2 / 2
| 2
eidos
"Thus , the finding in this study that UCHL1 / L3 inhibition is not as efficient in blocking viral replication as general inhibition of proteasome function or knockdown of ubiquitin is likely attributed to incomplete inhibition of DUBs by UCHL1 / L3 inhibitors ."
18612413
eidos
"Thus , it is speculated that DUB inhibition by UCHL1 / L3 inhibitors alone , in the absence of apparent inhibition of protein degradation , is not sufficient enough to block viral replication ."
18612413
UCHL1 activates ZUP1.
| 1
UCHL1 activates ZUP1. 1 / 1
| 1
eidos
"Although UCHL1 is identified as an important DUB , inhibition of UCHL1 alone has been shown to only partially block the activities of DUBs [ 41 ] ."
18612413
SRGN affects ZUP1
| 3
ZUP1 binds SRGN. 3 / 3
| 3
reach
"The final data collection and refinement statistics for the ZUFSP-Ub-Prg complex structure is shown in Table 1."
29576527
reach
"The final data collection and refinement statistics for the ZUFSP-Ub and Prg complex structure is shown in XREF_TABLE."
29576527
reach
"(H) Structural superposition of UFM1 onto the ZUFSP-Ub-Prg complex structure."
29576527
Mutagenesis affects ZUP1
| 3
Mutagenesis inhibits ZUP1. 3 / 3
| 3
eidos
"Using reporter assays , we found that blocking the DUB activity by mutagenesis did not completely abrogate the ability of USP15 to inhibit the type I IFN signaling pathway ( Fig. 6 ) ."
26061460
eidos
"Inhibition of DUB activity by mutagenesis did not abrogate interferon antagonism ."
26061460
eidos
"However , inhibition of DUB activity by mutagenesis means did not completely abrogate the ability of USP25 to block viral activation of the type I IFN signaling pathway ."
24260525
D1772A affects ZUP1
| 3
D1772A inhibits ZUP1. 3 / 3
| 3
eidos
"Structure-guided mutagenesis of MHV PLP2 reveals that D1772A disrupts 563 ubiquitin binding and reduces DUB activity ."
| DOI
eidos
"Structure-guided mutagenesis of MHV PLP2 reveals that D1772A disrupts ubiquitin binding and reduces DUB activity ."
32188728
eidos
"FIG 2 : Structure-guided mutagenesis of MHV PLP2 reveals that D1772A disrupts ubiquitin binding and reduces DUB activity ."
32188728
D1772A substitution coronavirus papain-like protease Ub-binding site affects ZUP1
| 3
D1772A substitution coronavirus papain-like protease Ub-binding site inhibits ZUP1. 3 / 3
| 3
eidos
"D1772A substitution in the coronavirus papain-like protease Ub-binding site 573 reduces DUB activity and interferon antagonism without reducing protease activity ."
| DOI
eidos
"D1772A substitution in the coronavirus papain-like protease Ub-binding site reduces DUB activity and interferon antagonism without reducing protease activity ."
32188728
eidos
"FIG 3 : D1772A substitution in the coronavirus papain-like protease Ub-binding site reduces DUB activity and interferon antagonism without reducing protease activity ."
32188728
CC.4 affects ZUP1
| 1 2
CC.4 inhibits ZUP1.
| 1 1
CC.4 inhibits ZUP1. 2 / 2
| 1 1
reach
"Slopes of linear portions of fluorescent signal formation were used to determine the velocity of substrate cleavage in the presence and absence of ubiquitin variant CC.4 (CC.4) which has been shown previously to inhibit DUB activity of CCHFV isolated OTU-domain [27]."
32497085
eidos
"DUB activity velocities were plotted versus CC.4 concentrations and fitted to a log ( inhibitor ) - versus-normalized-response - ( variable slope ) equation using GraphPad Prism 7.0 ( GraphPad Software , Inc ., San Diego , CA , USA ) to determine the IC50 values for the inhibition of DUB activity by CC.4 ."
32497085
CC.4 activates ZUP1.
| 1
CC.4 activates ZUP1. 1 / 1
| 1
reach
"Addition of OTU-specific inhibitor CC.4 blocked DUB activity of both enzymes."
32497085
Μ affects ZUP1
| 2
Μ inhibits ZUP1.
| 1
Μ inhibits ZUP1. 1 / 1
| 1
reach
"The anti-psychotic, phthalimide-based pimozide (3.30) is a selective, allosteric, low μM inhibitor of the DUB enzyme USP1–USP1 associated factor 1 (UAF1) complex [106]."
| PMC
Μ activates ZUP1.
| 1
Μ activates ZUP1. 1 / 1
| 1
reach
"Structures of non-selective DUB inhibitors.Structures of USP1/UAF1 inhibitors.Structures of a representative Novartis USP2 inhibitor and the cathepsin K inhibitor dutacatib.Structures of early USP7 inhibitors from Hybrigenics.USP7 IC50 4.2 μM USP7 IC 50 8.0 μM USP7 IC 50 0.42 μM USP47 IC 50 4.3 μM USP47 IC 50 8.7 μM USP47 IC 50 1.Structures of USP7 inhibitors from Progenra.Structures of recent USP7 inhibitors.Structures of USP8 inhibitors from Hybrigenics.Structures of a USP8 binder and two inhibitors of non-DUB cysteine proteases which advanced to clinical trials."
26852935
Ubiquitin interaction affects ZUP1
| 2
Ubiquitin interaction activates ZUP1. 2 / 2
| 2
eidos
"We included the following text in the discussion ; `` Interestingly , OtDUB UBD : ubiquitin interaction strongly promotes DUB activity at high OtDUB concentrations ."
32393759
eidos
"Interestingly , OtDUB UBD : ubiquitin interaction strongly promotes DUB activity at high OtDUB concentrations ."
32393759
Small-molecule affects ZUP1
| 2
Small-molecule activates ZUP1. 2 / 2
| 2
eidos
"They also used this reporter to assess DUB inhibition by small-molecule inhibitors in intact cells ."
32831622
eidos
"Additionally , we demonstrated that the cell-permeable DUB ABPs can be used in assessing the inhibition of DUBs by small-molecule inhibitors in intact cells ."
30240200
Recombinant enzymes nM assay buffer affects ZUP1
| 2
Recombinant enzymes nM assay buffer inhibits ZUP1. 2 / 2
| 2
eidos
"To assess DUB inhibition by biotinylated Ub-based probes , recombinant enzymes ( 50 nM ) in assay buffer were incubated with eight different probe concentrations ( 0-3 muM ) for 30 min at 37 degreesC ."
32953009
eidos
"To assess DUB inhibition by biotinylated Ub-based probes , recombinant enzymes ( 50 nM ) in assay buffer were incubated with eight different probe concentrations ( 0-3 mM ) for 30 min at 37 C."
32953009
PolyUb affects ZUP1
| 2
ZUP1 binds polyUb. 2 / 2
| 2
reach
"Having identified a UBZ domain in ZUFSP that binds polyUb, we asked whether the addition of this domain would confer DUB activity to the catalytic domain of ZUFSP."
29576527
reach
"We have here identified two unannotated UBDs within ZUFSP, the helical ZHA juxtaposed to the catalytic domain that binds the distal Ub and the UBZ domain that binds polyUb."
29576527
Mutation predicted catalytic cysteine aspartic acid residue alanine affects ZUP1
| 2
Mutation predicted catalytic cysteine aspartic acid residue alanine inhibits ZUP1. 2 / 2
| 2
eidos
"They showed that mutation of the predicted catalytic cysteine or aspartic acid residue to alanine leads to loss of DUB activity ( 23 , 24 ) ."
24512893
eidos
"They showed that mutation of the predicted catalytic cysteine or aspartic acid residue to alanine leads to loss of DUB activity ( Lindner et al ., 2005 , Barretto et al ., 2005 ) ."
24512893
Geometrical affects ZUP1
| 2
Geometrical activates ZUP1. 2 / 2
| 2
eidos
"Due to the geometrical differences between all Lys-linked diUb probes , the DUB will only be able to position the probes mimicking its natural substrates in such a way that the active site cysteine is able to react with the reactive element ."
30850060
eidos
"Due to the geometrical differences between al Lys-linked diUb probes , the DUB will only be able to position the probes mimicking its natural substrates in such a way that the active site cysteine is able to react with the reactive element ( see Fig. 1b ) ."
30178261
Biotinylated probes affects ZUP1
| 2
Biotinylated probes inhibits ZUP1. 2 / 2
| 2
eidos
"To assess DUB inhibition by biotinylated Ub-based probes , recombinant enzymes ( 50 nM ) in assay buffer were incubated with eight different probe concentrations ( 0-3 mM ) for 30 min at 37 C."
32953009
eidos
"To assess DUB inhibition by biotinylated Ub-based probes , recombinant enzymes ( 50 nM ) in assay buffer were incubated with eight different probe concentrations ( 0-3 muM ) for 30 min at 37 degreesC ."
32953009
ZUP1 affects ubiquitinated RIG-I STING
| 2
ZUP1 inhibits ubiquitinated RIG-I STING. 2 / 2
| 2
eidos
"Figure 4 : TGEV PL1 displays DUB activity that is dependent on its catalytic activity and reduces the ubiquitinated forms of RIG-I and STING ."
29201911
eidos
"HEK293T cells were transfected with TGEV PL1 , together with Flag-RIG-1 and Flag-STING for 24 h , TGEV PL1 displays DUB activity that is dependent on its catalytic activity and reduces the ubiquitinated forms of RIG-I and STING ."
29201911
eidos
"In fibroblasts derived from Leber Hereditary Optic Neuropathy ( LHON ) harboring the m.11778G > A mutation , DUb highly decreases reactive oxygen species ( ROS ) from affected and control cells [ 102 ] ."
33557229
eidos
"Furthermore , DUB inhibition did not increase ROS levels , nor elicit a strong NRF2-mediated antioxidant response ( based on expression of two canonical target genes NQO1 and GCLC ) ( Figures 4B , 4C and S4B ) ."
30799286
ZUP1 affects polyUb
| 2
ZUP1 binds polyUb. 2 / 2
| 2
reach
"Having identified a UBZ domain in ZUFSP that binds polyUb, we asked whether the addition of this domain would confer DUB activity to the catalytic domain of ZUFSP."
29576527
reach
"We have here identified two unannotated UBDs within ZUFSP, the helical ZHA juxtaposed to the catalytic domain that binds the distal Ub and the UBZ domain that binds polyUb."
29576527
ZUP1 affects ZUP1
| 2
ZUP1 inhibits ZUP1.
| 1
ZUP1 inhibits ZUP1. 1 / 1
| 1
eidos
"DUBs that are cysteine proteases harbor a reactive cysteine residue that can be oxidized by reactive oxygen species ( ROS ) , thus attenuating DUB activity ."
33511009
ZUP1 activates ZUP1.
| 1
ZUP1 activates ZUP1. 1 / 1
| 1
eidos
"When the DUB is inhibited by a DUB inhibitor , the upper band disappears or shows a lower band intensity [ 62,63 ] ."
32781716
ZUP1 affects ZC3H12A
| 2
ZUP1 activates ZC3H12A. 2 / 2
| 2
reach
"Taking our previously foundation together with the report by Liang et al. [21,22], we think that the DUB activation of MCPIP1 plays important role in its negatively regulation of IFN expression pathway, which is similar to A20 [12,[47], [48], [49]]."
29920243
reach
"Taking our previously foundation together with the report by Liang et al. [21, 22] , we think that the DUB activation of MCPIP1 plays important role in its negatively regulation of IFN expression pathway, which is similar to A20 [12,47e49] ."
29920243
ZUP1 affects VCP
| 2
VCP binds ZUP1. 2 / 2
| 2
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U-box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub-dependent proteolysis (Ghislain et al., 1996; Johnson et al., 1995) ."
17145306
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U‐box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub‐dependent proteolysis (Ghislain 1996, Johnson 1995)."
17145306
ZUP1 affects TCEAL1
2 |
TCEAL1 binds ZUP1. 2 / 2
2 |
biogrid
No evidence text available
26186194
biogrid
No evidence text available
28514442
ZUP1 affects STING1
| 1 1
ZUP1 inhibits STING1. 2 / 2
| 1 1
eidos
"All three DUBs seem to prevent STING from proteasome-dependent degradation through uncoupling K48-linked ubiquitination after DNA virus infection ."
33511009
reach
"Thus, these results are consistent with a role for viral DUB activity in antagonizing either the assembly or stability of STING dimers.Recent studies have revealed the arsenal of proteins that viruses use to evade and subvert recognition by pattern-recognition receptors (PRRs) or activation of signaling molecules that are designed to respond to infectious agents [45]."
22312431
ZUP1 affects STING dimers
| 2
ZUP1 inhibits STING dimers. 2 / 2
| 2
reach
"A previous report indicates that only the dimer form of STING is ubiquitinated [9], which coupled with our observation that PLPs with DUB activity reduce the accumulation of STING dimers, supports a role for DUB activity in negatively regulating STING."
22312431
reach
"Similar results were obtained when we evaluated PLpro-TM for disruption of STING dimers (Fig. S3) A previous report indicates that only the dimer form of STING is ubiquitinated [9], which coupled with our observation that PLPs with DUB activity reduce the accumulation of STING dimers, supports a role for DUB activity in negatively regulating STING."
22312431
ZUP1 affects SHCBP1
1 1 |
ZUP1 binds SHCBP1. 2 / 2
1 1 |
biogrid
No evidence text available
16189514
hprd
No evidence text available
16189514
ZUP1 affects SGSM3
| 2
ZUP1 binds SGSM3. 2 / 2
| 2
reach
"(B) Subset of ZUFSP interaction map showing proteins involved in DNA repair, DNA replication, and negative regulation of DNA recombination."
29576527
reach
"(F) ZUFSP interaction map, representing high confidence interacting proteins obtained from SAINT output filtered with 1% Bayesian false discovery rate (BFDR)."
29576527
ZUP1 affects RPA
| 2
ZUP1 ubiquitinates RPA.
| 1
ZUP1 leads to the ubiquitination of RPA. 1 / 1
| 1
reach
"ZUFSP interacts with and modulates ubiquitination of the replication protein A (RPA) complex."
29563501
ZUP1 binds RPA.
| 1
RPA binds ZUP1. 1 / 1
| 1
reach
"The DNA dependent binding of ZUFSP to the RPA complex was confirmed by co-immunoprecipitation experiments."
29476094
ZUP1 affects Protease
| 2
ZUP1 activates Protease. 2 / 2
| 2
reach
"PLpro is thought to antagonize the IFN response through its deubiquitinating enzyme (DUB) activity, which allows the protease to remove ubiquitin from a substrate."
31635238
reach
"In proteases such as those of CoV, the DUB activity may also contribute totheir cellular lifetimes.For reservoir species, an obvious rule or trend was not apparent."
34019767
ZUP1 inhibits Neoplasm Invasiveness. 2 / 2
| 2
reach
"It was further demonstrated that DUb inhibited LoVo cell proliferation, migration and invasion by upregulating SIRT2."
35177983
reach
"We found that DUb significantly inhibited the CRC cell migration and invasion inside Boyden Chambers in a dose-dependent manner (Figure 4)."
35177983
ZUP1 affects NFASC
| 2
ZUP1 inhibits NFASC. 2 / 2
| 2
reach
"A second DUB, A20 (also known as tumour necrosis factor‐α‐induced protein 3, TNFAIP3) negatively regulates NF‐κB signalling."
20073038
reach
"The YopJ DUB inhibits NF‐κB and mitogen‐activated protein kinase (MAPK) pathways, a function ascribed previously to its somewhat promiscuous deubiquitination of critical cellular proteins, such as TRAF2, TRAF6, and IkB."
17145306
ZUP1 affects MAVS
| 2
ZUP1 inhibits MAVS. 2 / 2
| 2
reach
"This enabled us, for the first time, to demonstrate that the DUB activity of MERS-CoV PL pro can suppress the MAVS-mediated induction of IFN-␤ expression.Cells, Antibodies, and Plasmids-HEK293T cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (FCS; Bodinco BV), 100 units/ml penicillin, 100 units/ml streptomycin, and 2 mM L-glutamine (cell culture medium and supplements were obtained from Lonza)."
25320088
reach
"Thisenabled us, for the first time, to demonstrate that the DUB activity of MERS-CoVPLpro can suppress the MAVS-mediated induction of IFN-βexpression.HEK293T cells were cultured in Dulbecco's modified Eagle's medium (DMEM)supplemented with 10% fetal calf serum (FCS; Bodinco BV), 100 units/mlpenicillin, 100 units/ml streptomycin, and 2 mml-glutamine (cell culture medium and supplements were obtainedfrom Lonza)."
25320088
ZUP1 affects ISG15
| 2
ZUP1 inhibits ISG15.
| 1
ZUP1 inhibits ISG15. 1 / 1
| 1
reach
"vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins."
30629698
ZUP1 activates ISG15.
| 1
ZUP1 activates ISG15. 1 / 1
| 1
reach
"Also as expected, CCHFV-OTU is inhibited by specific inhibitors of DUB enzymes corresponding to ubiquitin and ISG15 derivates coupled to aldehyde or vinyl sulfone [15À18]."
| PMC
ZUP1 affects Glioma
| 2
ZUP1 inhibits Glioma. 2 / 2
| 2
reach
"A report uncovered that the combination treatment of EDL-360 with DUb effectively suppressed glioma tumorigenesis by inducing cell death (Hosni-Ahmed et al., 2014)."
35177983
reach
"Recent study demonstrated that DUb combined with either EDL-360 or thialysine significantly inhibited the growth of human acute leukemia or glioma (Hosni-Ahmed et al., 2014)."
35177983
ZUP1 affects FBXW7
| 2
ZUP1 inhibits FBXW7. 2 / 2
| 2
reach
"In this review, we focus on discussing the specific roles of USP28 in cancer pathways, and their potential therapeutic values in cancer treatment.USP28 was the first FBW7-antagonizing DUB in an shRNA screen using c-MYC stability as a readout in human tumor cells16."
29415985
reach
"Below, we will review the mechanisms accounting for the involvement of USP28 in these pathways (Fig 3, Table 1 ), hence demonstrating its significance as a therapeutic target for cancer treatment.Disrupting physiological homeostasis of ubiquitination process USP28 was the first FBW7-antagonizing DUB in an shRNA screen using c-MYC stability as a readout in human tumor cells 16 ."
29415985
ZUP1 affects FANCD2
| 1 1
ZUP1 ubiquitinates FANCD2.
| 1
ZUP1 leads to the ubiquitination of FANCD2. 1 / 1
| 1
reach
"Remarkably, depletion of OTUB1 restored a pharmacologically disabled DSB response, indicating that targeting the OTUB1-E2 interaction might be an attractive route for the development of agents that bolster DSB repair.Another important example of the role played by DUBs in DNA repair relates to USP1, a DUB that modulates both FANCD2/FANCI and PCNA ubiquitylation [196], [197]."
21056014
ZUP1 activates FANCD2.
| 1
ZUP1 activates FANCD2. 1 / 1
| 1
eidos
"Another important example of the role played by DUBs in DNA repair relates to USP1 , a DUB that modulates both FANCD2 / FANCI and PCNA ubiquitylation [ 196 ] , [ 197 ] ."
21056014
ZUP1 affects Cdc48p
| 2
ZUP1 binds Cdc48p. 2 / 2
| 2
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U‐box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub‐dependent proteolysis (Ghislain 1996, Johnson 1995)."
17145306
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U-box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub-dependent proteolysis (Ghislain et al., 1996; Johnson et al., 1995) ."
17145306
ZUP1 affects Carcinogenesis
| 1 1
ZUP1 inhibits Carcinogenesis.
| 1
reach
"A report uncovered that the combination treatment of EDL-360 with DUb effectively suppressed glioma tumorigenesis by inducing cell death (Hosni-Ahmed et al., 2014)."
35177983
ZUP1 activates Carcinogenesis.
| 1
ZUP1 activates Carcinogenesis. 1 / 1
| 1
eidos
"Thus , DUB inhibitors are regarded as potential anti-cancer agents ( 180 ) To date , a number of DUB inhibitors have been identified to inhibit tumorigenesis ( 4 , 10 , 181 ) ."
33643919
VCP affects ZUP1
| 2
VCP binds ZUP1. 2 / 2
| 2
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U-box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub-dependent proteolysis (Ghislain et al., 1996; Johnson et al., 1995) ."
17145306
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U‐box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub‐dependent proteolysis (Ghislain 1996, Johnson 1995)."
17145306
USP14 affects ZUP1
| 2
USP14 inhibits ZUP1.
| 1
USP14 inhibits ZUP1. 1 / 1
| 1
reach
"In addition, loss of the DUB, USP14, reduced neurotransmitter release and increased surface expression of the GABA R (Jarome et al., 2013)."
34602983
USP14 deubiquitinates ZUP1.
| 1
USP14 deubiquitinates ZUP1. 1 / 1
| 1
reach
"Proteasomes function under tonic inhibitory conditions, possibly via the ubiquitin chain-trimming function of USP14, a proteasome-associated deubiquitinating enzyme (DUB)."
26041011
TP53BP1 affects ZUP1
| 2
TP53BP1 activates ZUP1. 2 / 2
| 2
reach
"Using cyclin A as a marker for S/G2-phase and 53BP1 as a DNA damage marker, we observed that both G1- and S/G2-phase cells displays increased 53BP1 signal in ZUFSP depleted cells, indicative of increased DNA breaks in both these cell-cycle phases (Figure 7D)."
29576527
reach
"Using cyclin A as a marker for S/G 2 -phase and 53BP1 as a DNA damage marker, we observed that both G 1 - and S/G 2 -phase cells displays increased 53BP1 signal in ZUFSP depleted cells, indicative of increased DNA breaks in both these cell-cycle phases (XREF_FIG D)."
29576527
TCEAL1 affects ZUP1
2 |
TCEAL1 binds ZUP1. 2 / 2
2 |
biogrid
No evidence text available
26186194
biogrid
No evidence text available
28514442
SHCBP1 affects ZUP1
1 1 |
ZUP1 binds SHCBP1. 2 / 2
1 1 |
biogrid
No evidence text available
16189514
hprd
No evidence text available
16189514
SGSM3 affects ZUP1
| 2
ZUP1 binds SGSM3. 2 / 2
| 2
reach
"(B) Subset of ZUFSP interaction map showing proteins involved in DNA repair, DNA replication, and negative regulation of DNA recombination."
29576527
reach
"(F) ZUFSP interaction map, representing high confidence interacting proteins obtained from SAINT output filtered with 1% Bayesian false discovery rate (BFDR)."
29576527
Picornaviridae family affects ZUP1
| 2
Picornaviridae family increases the amount of ZUP1.
| 1
Picornaviridae family increases the amount of ZUP1. 1 / 1
| 1
reach
"For example, the 3C protein of enterovirus 71 (EV71), a member of the Picornaviridae family that causes hand, foot and mouth disease, and occasionally severe central nervous system diseases, downregulates the host microRNA miR-526a to increase the expression of the cellular DUB enzyme CYLD, thus inhibiting the activation of RIG-I 74 ."
27174148
Picornaviridae family decreases the amount of ZUP1.
| 1
Picornaviridae family decreases the amount of ZUP1. 1 / 1
| 1
reach
"For example, the 3C protein of enterovirus 71 (EV71), a member of the Picornaviridae family that causes hand, foot and mouth disease, and occasionally severe central nervous system diseases, downregulates the host microRNA miR-526a to increase the expression of the cellular DUB enzyme CYLD, thus inhibiting the activation of RIG-I 74 ."
27174148
PRDX5 affects ZUP1
| 2
PRDX5 deubiquitinates ZUP1. 2 / 2
| 2
reach
"PLP deubiquitinating (DUB) activity has been demonstrated in several CoV species, and acts directly and indirectly on several signal molecules in the IRF-3-dependent IFN induction pathway including retinoic acid inducible gene-I (RIG-I), tumor necrosis factor receptor-associated factor 3 (TRAF3), TANK-binding kinase 1 (TBK1) and STING [30, 31]."
30248143
reach
"One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB) activity, and antagonizes the induction of type I interferon (IFN)."
20181693
OtDUB UBD affects ZUP1
| 2
OtDUB UBD activates ZUP1. 2 / 2
| 2
eidos
"Interestingly , OtDUB UBD : ubiquitin interaction strongly promotes DUB activity at high OtDUB concentrations ."
32393759
eidos
"We included the following text in the discussion ; `` Interestingly , OtDUB UBD : ubiquitin interaction strongly promotes DUB activity at high OtDUB concentrations ."
32393759
Msn2 affects ZUP1
| 2
Msn2 inhibits ZUP1. 2 / 2
| 2
eidos
"Further investigations showed that the transcription of UBP6 and other DUB genes was not significantly changed in MSN2-OE cells , indicating that Msn2 does not repress UBP6 and other DUB genes transcriptionally ( Mat Nanyan et al ., 2019b ) ."
32411186
eidos
"( B ) Secondly , a high level of Msn2 may activate the gene expression of DUB repressors such as Rfu1-like protein ( s ) , leading to a reduced or loss function of DUBs ."
32411186
ML364 affects ZUP1
| 1 1
ML364 inhibits ZUP1. 2 / 2
| 1 1
reach
"Pyr-41 was used to inhibit ubiquitin recruitment by E1 ligase preventing ubiquitination; VCP function was blocked by DBeQ and EerI; DUB activity was suppressed by ML364; and proteasomal degradation was avoided by treating with MG132 75,92-94 ."
33986255
eidos
"Pyr-41 was used to inhibit ubiquitin recruitment by E1 ligase preventing ubiquitination ; VCP function was blocked by DBeQ and EerI ; DUB activity was suppressed by ML364 ; and proteasomal degradation was avoided by treating with MG13275 ,92 -94 ."
33986255
Interferon affects ZUP1
| 2
Interferon inhibits ZUP1.
| 1
Interferon inhibits ZUP1. 1 / 1
| 1
reach
"By utilizing DUB activity of ORF64, MHV68 blocked viral DNA induced, STING-mediated IFN production [19]."
31208841
Interferon activates ZUP1.
| 1
Interferon activates ZUP1. 1 / 1
| 1
reach
"Mutating the catalytic residue of USP25 was sufficient to block USP25's effect on IFNβ induction, supporting that IFN-β suppression via USP25 is DUB activity dependent [20] ."
31208841
F1812A mutant affects ZUP1
| 2
F1812A mutant inhibits ZUP1. 2 / 2
| 2
eidos
"Error bars , S.D. Importantly , the F1812A mutant leads to a substantial decrease ( 3 % remaining activity ) in its DUB activity , whereas 50 % of its activity with Z-RLRGG-AMC is maintained ."
26296883
eidos
"Importantly , the F1812A mutant leads to a substantial decrease ( 3 % remaining activity ) in its DUB activity , whereas 50 % of its activity with Z-RLRGG-AMC is maintained ."
26296883
DUB inhibitors affects ZUP1
| 2
DUB inhibitors inhibits ZUP1.
| 1
DUB inhibitors inhibits ZUP1. 1 / 1
| 1
reach
"Some of its members, such as RA-9 (3.29, Figure 3 .5), are partially selective DUB inhibitors, inhibiting >50% overall DUB activity in cervical cancer HeLa cells at 10 mM [105] ."
| PMC
DUB inhibitors activates ZUP1.
| 1
DUB inhibitors activates ZUP1. 1 / 1
| 1
reach
"Some of its members, such as RA-9 (3.29, Figure 3.5), are partially selective DUB inhibitors, inhibiting >50% overall DUB activity in cervical cancer HeLa cells at 10 μM [105]."
| PMC
Cdc48p affects ZUP1
| 2
ZUP1 binds Cdc48p. 2 / 2
| 2
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U‐box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub‐dependent proteolysis (Ghislain 1996, Johnson 1995)."
17145306
reach
"Cdc48p/p97 can simultaneously bind Ufd2p, a U-box E3 that catalyzes polyubiquitin chain extension, and one of two factors that can counteract its action: Otu1p, a DUB, and Ufd3p protein, a WD40 repeat protein of unknown function that has been shown to be required for Ub-dependent proteolysis (Ghislain et al., 1996; Johnson et al., 1995) ."
17145306
£i~rinogen affects ZUP1
| 1
ZUP1 binds £i~rinogen. 1 / 1
| 1
reach
"DUB to its steric configuration fib~inogen interacts with red blood cells -mainly in the small vessel sustem, wh~ce shear stress is lowcausing revecsible aggn~gation, well known as "rculeaux" or "sludge" phenomenon, Hence sludging can be the reason o£ severe ismhemia, and the tendency to aggregate cotTelstas well with concentrations cf £i~rinogen, there is a need to qcantifg the corce~trstion of £ibFirogem."
2302464
Vinclozolin affects ZUP1
1 |
Vinclozolin increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
23034163
Ubiquitin variants affects ZUP1
| 1
Ubiquitin variants inhibits ZUP1. 1 / 1
| 1
eidos
"Previously , ubiquitin variants ( Ubv ) have been developed to selectively inhibit DUBs by binding to the S1 pocket ( Zhang et al , 2017 ; Gorelik & Sidhu , 2017 ) ."
| DOI
Trichloroethene affects ZUP1
1 |
Trichloroethene methylates ZUP1. 1 / 1
1 |
ctd
No evidence text available
27618143
TriUb affects ZUP1
| 1
TriUb activates ZUP1. 1 / 1
| 1
reach
"In scenario 2, the DUB engages the triUb substrate exclusively in an exo-binding mode that leads to the labeling of DUB by the triUb probe."
30914461
Suramin affects ZUP1
| 1
Suramin inhibits ZUP1. 1 / 1
| 1
eidos
"While the mechanism of suramin inhibition is beyond the scope of this study , the IC50 results indicate a possibility that suramin is inhibiting BPLF1 and other DUBs in a nonspecific manner ."
31711927
Sunitinib affects ZUP1
1 |
Sunitinib increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
31533062
Such affects ZUP1
| 1
Such activates ZUP1. 1 / 1
| 1
eidos
"A major limitation of this methodology is that the results are not readily extrapolatable to the substrate preference of a DUB in a more complex environment , such as cell-lysate , which might modulate DUB activity and preference due to other factors present in such samples ."
30850060
Succimer affects ZUP1
1 |
Succimer increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
26378955
Substrate binding affects ZUP1
| 1
Substrate binding activates ZUP1. 1 / 1
| 1
eidos
"] Additionally , substrate binding may promote DUB activation , thereby enabling fine-tuning of linkage specificity ."
33511009
Site MERS-CoV PL pro affects ZUP1
| 1
Site MERS-CoV PL pro inhibits ZUP1. 1 / 1
| 1
eidos
"https://doi.org/10.1101/751578 doi : bioRxiv preprint 312 In our previous work , we described amino acid substitutions in the Ub-binding site of MERS-CoV 313 PL pro that specifically disrupt its DUB activity without affecting the overall proteolytic activity ( 65 ) wt rMERS-CoV on both cell lines ( Fig 1 ) ."
| DOI
Rutin affects ZUP1
| 1
Rutin inhibits ZUP1. 1 / 1
| 1
eidos
"GRL-0167 , hypericin , and rutin , in order , inhibited DUB activity in another study [ 80 ] ."
33669054
Removal polar groups affects ZUP1
| 1
Removal polar groups activates ZUP1. 1 / 1
| 1
eidos
"Finally , DUB activity can actually be increased by the removal of polar groups and maintaining only apolar side chains ."
32732284
Quinolone affects ZUP1
| 1
Quinolone deubiquitinates ZUP1. 1 / 1
| 1
reach
"Despite having similar molecular size and functionality, the diterpene quinolone tanshinone derivatives, 1-6, inhibit the SARS-CoV PL pro isomerization slow-binding mode, whereas the abietane type derivative, 7, is active against PL pro through the simple slow-binding mode.PL pro , located within nsp3, cleaves at nsp1/2, nsp2/3 and nsp3/4 boundaries using the consensus motif LXGG, along with a consensus cleavage sequence of cellular deubiquitinating (DUB) enzymes."
22884354
Protease inhibitor affects ZUP1
| 1
Protease inhibitor inhibits ZUP1. 1 / 1
| 1
reach
"Furthermore, addition of a protease inhibitor that blocks both protease and DUB activity [52] failed to abrogate the PLP inhibition on activation of IRF-3 dependent promoters [14]."
22312431
Propensity be connected consistency survey findings globe affects ZUP1
| 1
Propensity be connected consistency survey findings globe activates ZUP1. 1 / 1
| 1
eidos
"So connected is this generation that their propensity to be digitally connected to one another and the consistency of the survey findings across the globe led Barna ( 2019 ) to dub today 's 18 to 35-year-olds the `` connected generation '' ."
| PMC
Probe affects ZUP1
| 1
Probe inhibits ZUP1. 1 / 1
| 1
eidos
"Kinetic analysis of DUB inhibition by Ub probes ."
32953009
Potential accessory domain affects ZUP1
| 1
Potential accessory domain activates ZUP1. 1 / 1
| 1
eidos
"We cloned the N-terminal domain of OtDUB from genomic DNA of the O. tsutsugamushi Ikeda isolate and included residues past the putative DUB domain to examine a potential accessory domain that could modulate DUB activity 11 , 18 ."
32393759
Position fusing C terminus ZUFSP affects ZUP1
| 1
Position fusing C terminus ZUFSP inhibits ZUP1. 1 / 1
| 1
eidos
"Indeed , changing the position of UBZ by fusing it to the C terminus of ZUFSP resulted in loss of DUB activity , supporting our notion that the UBZ may form the proximal Ub binding site ( Figure S5A ) ."
29576527
Point mutations binding affects ZUP1
| 1
Point mutations binding activates ZUP1. 1 / 1
| 1
eidos
"They establish that point mutations aimed at improving Ub binding do result in a considerably increased DUB activity ."
32732284
Phosphorylation affects ZUP1
| 1
eidos
"Phosphorylation also inhibits certain E2s , E3s and DUBs and modulates the ubiquitylation cycle [ 102 ] ."
33114409
Phosphorylation Ser381 mediated IKKbeta affects ZUP1
| 1
Phosphorylation Ser381 mediated IKKbeta activates ZUP1. 1 / 1
| 1
eidos
"Phosphorylation sites of A20 contains Ser381 , Ser480 , Ser565 , and Thr625 , and phosphorylation at Ser381 mediated by IKKbeta can improve DUB activity ."
| PMC
Phorbol 13-acetate 12-myristate decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
25613284
Perfluorooctane-1-sulfonic acid decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
27153767
Pentachlorophenol affects ZUP1
1 |
Pentachlorophenol increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
23892564
Nature conformational affects ZUP1
| 1
Nature conformational activates ZUP1. 1 / 1
| 1
eidos
"What is the nature of conformational changes that activate DUBs ?"
19489724
Mutations predicted catalytic sites affects ZUP1
| 1
Mutations predicted catalytic sites inhibits ZUP1. 1 / 1
| 1
eidos
"The mutations of the predicted catalytic sites ( Asp42 , Cys45 and His148 ) resulted in the loss of DUB activity , demonstrating these three residues were required for enzyme activity ."
33146853
Mutations catalytic residues PLP-TM Cys1274Ser His1437Lys affects ZUP1
| 1
Mutations catalytic residues PLP-TM Cys1274Ser His1437Lys inhibits ZUP1. 1 / 1
| 1
eidos
"In addition , mutations of the catalytic residues of PLP-TM , Cys1274Ser and His1437Lys , reduced DUB activity against Ub - , K48-and K63-conjugated proteins , indicating that the DUB activity of the PLP-TM wild-type protein is not completely dependent on its catalytic activity ."
28316013
Mutation s surface affects ZUP1
| 1
Mutation s surface inhibits ZUP1. 1 / 1
| 1
eidos
"The ubiquitin-binding surface is distant from the catalytic site , which explains how mutation ( s ) on this surface can reduce DUB activity without affecting polyprotein cleavage ."
23891306
Mutation residue Glu168 affects ZUP1
| 1
Mutation residue Glu168 inhibits ZUP1. 1 / 1
| 1
eidos
"Similarly , the structure and site-directed mutagenesis suggest that mutation of the residue Glu168 , which plays an important role in Ub core recognition , can cause a severe loss of DUB activity ."
24531491
Mutation domain affects ZUP1
| 1
Mutation domain inhibits ZUP1. 1 / 1
| 1
eidos
"A mutation in the SAP domain ( I83A / L86A ) , was previously reported to abolish the ability of Lpro to suppress type I IFN expression , to degrade signaling proteins ( i.e. NF-kappaB p65 , IRF3 and IRF7 ) , and to disrupt its DUB activity [ 36,37,39 ] , and was therefore included in our screening ."
32667958
Mutation S2 binding site affects ZUP1
| 1
Mutation S2 binding site inhibits ZUP1. 1 / 1
| 1
eidos
"Indeed , mutation of the S2 binding site results in slightly reduced DUB activity ( Figure S5F ) ."
29576527
Mutation I847D affects ZUP1
| 1
Mutation I847D inhibits ZUP1. 1 / 1
| 1
eidos
"Indeed , mutating Ile847 to Ala , which conserves its apolar properties , has a significant but mild effect on DUB activity , both in vitro and in vivo , whereas addition of a negative charge in this region ( mutation I847D ) drastically decreased DUB activity ( 28 , 34 ) ."
32732284
Mutating residue Glu156 Lys NL63-PLP2 affects ZUP1
| 1
Mutating residue Glu156 Lys NL63-PLP2 inhibits ZUP1. 1 / 1
| 1
eidos
"Consequently , we predict that mutating residue Glu156 to Lys in NL63-PLP2 should lead to loss of DUB activity ."
22004941
Mutants affects ZUP1
| 1
Mutants activates ZUP1. 1 / 1
| 1
eidos
"Nevertheless , the interacting surface is both small and suboptimal in its composition , as shown by mutants that improve the DUB activity ( Fig. 3A ) ."
32732284
Methylparaben affects ZUP1
1 |
Methylparaben increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
31745603
Methyl affects ZUP1
| 1
Methyl activates ZUP1. 1 / 1
| 1
reach
"Monoubiquitin probes targeting the S1 pocket; internal diubiquitin probes targeting S1-S1 0 pockets; terminal diubiquitin probes targeting S1-S2 pockets; Ub-substrate probes targeting S1-S1 0 pockets.The desired irreversible DUB ABPs were synthesized by chemical ligation of the reactive groups (methyl (E)-4-aminobut-2-enoate et al.) with HA-Ub 1-75 -MESNA and purified by cation exchange chromatography."
| PMC
Methyl methanesulfonate increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
23649840
Magnetite nanoparticle increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
26378955
Linked polyubiquitin chains phosphorylation A20 Ser381 affects ZUP1
| 1
Linked polyubiquitin chains phosphorylation A20 Ser381 activates ZUP1. 1 / 1
| 1
eidos
"The OTU domain of A20 functions as a DUB that cleaves K63 - - linked polyubiquitin chains , and phosphorylation of A20 at Ser381 , which is mediated by IKKbeta , can improve its DUB activity ."
| PMC
Ligand affects ZUP1
| 1
Ligand binds ZUP1. 1 / 1
| 1
reach
"A full description of our findings, along with X-ray structures of other DUB/ligand complexes, will be the subject of a future publication."
26852935
Lethal several point mutations affects ZUP1
| 1
Lethal several point mutations activates ZUP1. 1 / 1
| 1
eidos
"On the other hand , the fact that the cis-cleavage activity is not required for PRRSV replication suggests that the lethal phenotype of several point mutations ( D85N , D85R , T88R , and D91R ) , which blocked both DUB and cis-activity , is not due to a block in cis-cleavage activity , but may be linked to the inactivation of PLP2 DUB activity ."
31561412
Lead diacetate affects ZUP1
1 |
Lead diacetate increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
22641619
KDa affects ZUP1
| 1
KDa activates ZUP1. 1 / 1
| 1
eidos
"Among the 89 DUBs used for the cell-free protein synthesis , only one DUB , PRPF8 , was not obtained , probably due to its large molecular weight ( 274 kDa ) ."
| PMC
Jinfukang affects ZUP1
1 |
Jinfukang decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
27392435
Ionomycin affects ZUP1
1 |
Ionomycin decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
25613284
Involvement cancer pathologies affects ZUP1
| 1
Involvement cancer pathologies activates ZUP1. 1 / 1
| 1
eidos
"Due to their protease activity and their involvement in cancer pathologies , DUBs are emerging as potential targets for pharmacological interference in the ubiquitin regulatory machinery ( 11-13 ) ."
30962318
Interactions affects ZUP1
| 1
Interactions activates ZUP1. 1 / 1
| 1
eidos
"Structural studies of DUBs with di-ubiquitin have demonstrated that in addition to the peptide flanking the ubiquitylated residues , more extensive interactions between DUBs and the proximal ubiquitin in the chain also contribute to the recognition by DUBs ."
27613052
Inhibitor affects ZUP1
| 1
Inhibitor inhibits ZUP1. 1 / 1
| 1
eidos
"The residual activity observed in lysates treated with 50 muM PR-619 is an indication of incomplete inhibition of DUB activity by the inhibitor , suggesting that higher concentrations of the inhibitor would be needed to further decrease the level of DUB activity until a complete inhibition be potentially reached ."
32831622
Indometacin affects ZUP1
1 |
Indometacin increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
28628672
Hypericin affects ZUP1
| 1
Hypericin inhibits ZUP1. 1 / 1
| 1
eidos
"GRL-0167 , hypericin , and rutin , in order , inhibited DUB activity in another study [ 80 ] ."
33669054
Hsa-miR-203a-3p affects ZUP1
1 |
Hsa-miR-203a-3p decreases the amount of ZUP1. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22291592
Host affects ZUP1
| 1
Host activates ZUP1. 1 / 1
| 1
eidos
"Ub and ISG15 are both involved in signaling pathways recognized by the host which further stimulates the innate and anti-viral response.28 , 38 The DUB and deISGYlating activities assists in evasion of the host-innate immune system ."
32324951
Gold atom affects ZUP1
1 |
Gold atom decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
25523186
Glycidol affects ZUP1
1 |
Glycidol decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
24915197
Exposing carbonyl group nucleophilic attack SH group cysteine affects ZUP1
| 1
Exposing carbonyl group nucleophilic attack SH group cysteine inhibits ZUP1. 1 / 1
| 1
eidos
"RA-9 is a non-specific inhibitor that irreversibly inhibits DUBs by exposing its carbonyl group to a nucleophilic attack from the SH - group of cysteine ( 11 ) ."
32236606
Existing toolkit affects ZUP1
| 1
Existing toolkit activates ZUP1. 1 / 1
| 1
eidos
"The novel probes developed by Flierman et al. ( 2016 ) are an exciting addition to the existing toolkit that will allow us to study DUBs that use additional S2 site interactions ."
27105279
Dicrotophos affects ZUP1
1 |
Dicrotophos decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
28302478
Dexamethasone affects ZUP1
1 |
Dexamethasone increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
28628672
Design pro mutations affects ZUP1
| 1
Design pro mutations inhibits ZUP1. 1 / 1
| 1
eidos
"23 In previous work , we determined the crystal structure of MERS-CoV PL pro in complex with ubiquitin , 24 facilitating the design of PL pro mutations that impair DUB activity without affecting viral polyprotein 25 cleavage ."
| DOI
Design PLpro mutations affects ZUP1
| 1
Design PLpro mutations inhibits ZUP1. 1 / 1
| 1
eidos
"In previous work , we determined the crystal structure of MERS-CoV PLpro in complex with ubiquitin , facilitating the design of PLpro mutations that impair DUB activity without affecting viral polyprotein cleavage ."
| DOI
Decabromodiphenyl ether increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
23640034
Cysteine affects ZUP1
| 1
Proteasome binds ZUP1 and cysteine. 1 / 1
| 1
reach
"The first of these ubiquitin ABPs was ubiquitin-nitrile, which allowed the labeling of a proteasome-bound cysteine dependent DUB [36]."
25461387
Cyclosporin A affects ZUP1
1 |
Cyclosporin A increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
25562108
Copper(II) sulfate affects ZUP1
1 |
Copper(II) sulfate increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
19549813
Conjugation ubiquitin side-chain residue lysine targeted protein15 affects ZUP1
| 1
Conjugation ubiquitin side-chain residue lysine targeted protein15 inhibits ZUP1. 1 / 1
| 1
eidos
"Some DUBs recognize and cleave the peptide bond between the C-terminus of ubiquitin and the N-terminus of target proteins as a result of N-terminal ubiquitylation or linear ubiquitin chains21 ( Fig. 1d ) , while other DUBs are restricted to the iso-peptide bonds as a result of the conjugation of ubiquitin to the side-chain residue of ( usually ) lysine at the targeted protein15 ,16 ( Fig. 1d ) ."
33483467
Cisplatin affects ZUP1
1 |
Cisplatin decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
27392435
Chromatin bound proteins affects ZUP1
| 1
Chromatin bound proteins activates ZUP1. 1 / 1
| 1
eidos
"These DUBs are localized to sites of action by interaction with other chromatin bound proteins that act as scaffolds and activate the DUB activity ."
19489724
Charge affects ZUP1
| 1
Charge activates ZUP1. 1 / 1
| 1
eidos
"Indeed , mutating Ile847 to Ala , which conserves its apolar properties , has a significant but mild effect on DUB activity , both in vitro and in vivo , whereas addition of a negative charge in this region ( mutation I847D ) drastically decreased DUB activity ( 28 , 34 ) ."
32732284
Cell-lysate affects ZUP1
| 1
Cell-lysate activates ZUP1. 1 / 1
| 1
eidos
"A major limitation of this methodology is that the results are not readily extrapolatable to the substrate preference of a DUB in a more complex environment , such as cell-lysate , which might modulate DUB activity and preference due to other factors present in such samples ."
30850060
Cell cycle affects ZUP1
| 1
Cell cycle inhibits ZUP1. 1 / 1
| 1
reach
"[57] [58] [59] Our findings rationalize that similar to HCMV, other DUB-encoding viruses may perturb normal cell cycle or apoptotic pathways by inhibiting I-IFN synthesis."
28981114
Catalytic residues Cys PLP2 affects ZUP1
| 1
Catalytic residues Cys PLP2 inhibits ZUP1. 1 / 1
| 1
eidos
"HEK-293T cells were co-transfected with a plasmid expressing M or GP5 protein along with a plasmid expressing wild type ( WT ) nsp2TF or the nsp2TF-C / H > A mutant , in which both catalytic residues ( Cys and His ) of PLP2 were substituted with Ala to eliminate the DUB activity [ 20 ] ."
33735221
Calcium(2+) affects ZUP1
| 1
Calcium(2+) inhibits ZUP1. 1 / 1
| 1
reach
"By employing extracellular and/or intracellular calcium chelating compounds, it is possible to infect cells in Ca depleted conditions and probe resulting infectivity (Dubé et al., 2016)."
32272173
Bisphenol A affects ZUP1
1 |
Bisphenol A increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
25181051
reach
"[57] [58] [59] Our findings rationalize that similar to HCMV, other DUB-encoding viruses may perturb normal cell cycle or apoptotic pathways by inhibiting I-IFN synthesis."
28981114
Binding S1 pocket affects ZUP1
| 1
Binding S1 pocket inhibits ZUP1. 1 / 1
| 1
eidos
"Previously , ubiquitin variants ( Ubv ) have been developed to selectively inhibit DUBs by binding to the S1 pocket ( Zhang et al , 2017 ; Gorelik & Sidhu , 2017 ) ."
| DOI
Benzo[a]pyrene diol epoxide I decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
20382639
Benzene affects ZUP1
1 |
Benzene increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
19162166
Arsenite(1-) affects ZUP1
| 1
Arsenite(1-) activates ZUP1. 1 / 1
| 1
reach
"An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity."
34572530
Arginine mutation key residue core domain binding affects ZUP1
| 1
Arginine mutation key residue core domain binding inhibits ZUP1. 1 / 1
| 1
eidos
"As mimicking the equivalent residue of MERS-CoV PLpro , the arginine mutation of a key residue for Ub core domain binding , Glu168 , can result in unstable binding of SARS-CoV PLpro and Ub and significant loss of DUB activity [ 12 ] ."
24898546
Are redox cycling affects ZUP1
| 1
Are redox cycling inhibits ZUP1. 1 / 1
| 1
eidos
"It is likely that 14 and 15 are redox cycling compounds ( RCCs ) which inhibit USP1 and other DUBs through oxidation of the catalytic cysteine ."
26852935
Applying appropriate inhibitors molecules affects ZUP1
| 1
Applying appropriate inhibitors molecules inhibits ZUP1. 1 / 1
| 1
eidos
"Since the degradation of tumor suppressors and stabilization of oncoproteins by either negative regulation by E3 ligases or positive regulation of DUBs , respectively , promote tumorigenesis , it is necessary to suppress these DUBs by applying appropriate inhibitors or small molecules ."
34201062
Alpha beta-unsaturated carbonyl prostaglandins affects ZUP1
| 1
Alpha beta-unsaturated carbonyl prostaglandins inhibits ZUP1. 1 / 1
| 1
eidos
"USP5 / 7/8/13 / 14/15/22 Inhibitors Inspired by the discovery that the alpha , beta-unsaturated carbonyl in prostaglandins could react with the catalytic cysteine of DUBs to form covalent bonds and result in the inhibition of the DUBs , curcusone D ( Figure 12 ) was reported as a novel USPs inhibitor [ 127 ] ."
33925279
Aflatoxin B1 affects ZUP1
1 |
Aflatoxin B1 increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
19770486
ZUP1 affects £i~rinogen
| 1
ZUP1 binds £i~rinogen. 1 / 1
| 1
reach
"DUB to its steric configuration fib~inogen interacts with red blood cells -mainly in the small vessel sustem, wh~ce shear stress is lowcausing revecsible aggn~gation, well known as "rculeaux" or "sludge" phenomenon, Hence sludging can be the reason o£ severe ismhemia, and the tendency to aggregate cotTelstas well with concentrations cf £i~rinogen, there is a need to qcantifg the corce~trstion of £ibFirogem."
2302464
ZUP1 affects viral
| 1
ZUP1 inhibits viral. 1 / 1
| 1
eidos
"Altogether , our studies indicate that abolishing / reducing the deISGylase / DUB activity of Lpro causes viral attenuation independently of its ability to block expression of IFN and ISGs mRNA ."
32295921
ZUP1 affects viral life cycle
| 1
eidos
"DUB inhibitors further decreases the viral replication when used together with proteasome inhibitors through the additional reduction of recycled free ubiquitin ."
18612413
ZUP1 affects viral infectivity plant cells
| 1
ZUP1 activates viral infectivity plant cells. 1 / 1
| 1
eidos
"Finally , we show that this DUB activity contributes to viral infectivity in plant cells ."
22117220
ZUP1 affects viral accumulation single cells whole plants
| 1
ZUP1 activates viral accumulation single cells whole plants. 1 / 1
| 1
eidos
"Introduction of mutations into the viral genome revealed that the DUB activity contributes to the extent of viral RNA accumulation both in single cells and in whole plants ."
29117247
reach
"In particular, the role of robust DUB activity in promoting viral replication and conferring virulence in CCHFV and SARS-CoV emphasizes the impact of the respective proteases and highlights the emerging importance of understanding their effects when considering potential pathogenicity and therapeutic strategies.With the almost perfectly conserved sequence of Ub, it is not surprising that tick-borne nairoviruses from disparate taxa possess notable DUB activity."
30629698
ZUP1 affects unanchored ubiquitin chains
| 1
ZUP1 activates unanchored ubiquitin chains. 1 / 1
| 1
eidos
"This is because DUBs such as ataxin-3 [ 63 ] and Poh1 [ 12 ] that generate unanchored ubiquitin chains are required for HDAC6-mediated aggresome processing ."
27783058
ZUP1 affects unanchored polyubiquitin chains
| 1
ZUP1 activates unanchored polyubiquitin chains. 1 / 1
| 1
eidos
"Some DUBs produce unanchored polyubiquitin chains that regulate aggresome processing and innate immunity ."
27783058
ZUP1 affects ubiquitylation is dynamic modification
| 1
ZUP1 inhibits ubiquitylation is dynamic modification. 1 / 1
| 1
eidos
"Indeed , ubiquitylation is a dynamic modification that is reversed by dedicated proteases called deubiquitinases , or DUBs ."
29576527
ZUP1 affects ubiquitination process
| 1
ZUP1 inhibits ubiquitination process. 1 / 1
| 1
eidos
"DUBs recognize ligase E3 and remove the Ub bound to the target protein , thereby reversing the ubiquitination process [ 24 ] ."
32897241
ZUP1 affects ubiquitination p53
| 1
ZUP1 inhibits ubiquitination p53. 1 / 1
| 1
eidos
"The ubiquitination of p53 can be reversed by DUBs , a group of enzymes that control the extent of p53 ubiquitination through deubiquitinating p53 ."
33767588
ZUP1 affects ubiquitination cargos
| 1
ZUP1 activates ubiquitination cargos. 1 / 1
| 1
eidos
"DUBs therefore interact with ESCRT components to modulate the ubiquitination status of cargos , or to that of the components of the machinery to control the function of the ESCRT complex and the fate of the ubiquitinated cargo ( Wright et al ., 2011 ) ."
32528512
ZUP1 affects ubiquitination RIG-I TBK1 TRAF3 TRAF6
| 1
ZUP1 inhibits ubiquitination RIG-I TBK1 TRAF3 TRAF6. 1 / 1
| 1
eidos
"Lpro also acts as a deubiquitinating enzyme ( DUB ) that inhibits the ubiquitination of RIG-I , TBK1 , TRAF3 , and TRAF6 to suppress the signal transduction of RLR pathway ( 128 ) ."
33717061
ZUP1 affects ubiquitin-proteasome pathway
| 1
ZUP1 activates ubiquitin-proteasome pathway. 1 / 1
| 1
eidos
"In addition , the ubiquitin-proteasome pathway ( UPP ) regulates p53 stability and is modulated by DUBs that can eliminate ubiquitin from p53 ."
33767588
ZUP1 affects ubiquitin editing
| 1
ZUP1 activates ubiquitin editing. 1 / 1
| 1
eidos
"Pirk controls amyloid fibril stability while DUBs and a yet-to-be identified E3s drive amyloid disassembly , ubiquitin editing and Imd turnover via the proteasome ."
30857831
ZUP1 affects ubiquitin chain editing
| 1
ZUP1 activates ubiquitin chain editing. 1 / 1
| 1
eidos
"Second , in consort with the E3 ligases , DUBs mediate ubiquitin chain editing , which can alter the ubiquitin signal or protein stability ."
33195472
ZUP1 affects transformation cervical cancer
| 1
ZUP1 activates transformation cervical cancer. 1 / 1
| 1
eidos
"Results Increased USP13 expression in pre-malignant cervical disease and cervical cancer To investigate whether DUBs contribute to transformation in cervical cancer , we analysed the cervical cancer dataset from The Cancer Genome Atlas ( TCGA ) [ 34 ] ."
33627786
ZUP1 affects transcriptional
| 1
ZUP1 activates transcriptional. 1 / 1
| 1
eidos
"Notably , USP7 has been identified as the DUB that deubiquitylates FOXO4 and modulates its transcriptional activity in response to oxidative stress [ 98 ] , making USP7 a prime controller of oxidative stress responses that are frequent hallmarks of tumours and are often associated with the DDR defects [ 99 ] ."
23712866
reach
"Moreover, USP16 is a potent antagonist of Polycomb-dependent repression of gene expression [192] and was recently shown to be a DUB that enables the de-repression of gene transcription following DSB repair [112]."
21056014
ZUP1 affects toxicity combined DUB GCLC
| 1
ZUP1 activates toxicity combined DUB GCLC. 1 / 1
| 1
eidos
"It is likely that the inhibition of multiple DUBs contributes to the toxicity of combined DUB and GCLC suppression ."
30799286
ZUP1 affects supercomplexes
| 1
ZUP1 activates supercomplexes. 1 / 1
| 1
eidos
"They concluded that DUb can enhance the activities of supercomplexes such as I / III and II / III but is not determinant in the activities of the individual complexes , I , III , and IV , or in the rate of oxygen consumption , which was completely unaffected by DUb ."
33557229
ZUP1 affects substrate
| 1
ZUP1 activates substrate. 1 / 1
| 1
eidos
"DUB inhibitors may stimulate the degradation of some substrates by directly inhibiting their deubiquitination , or , as discussed , may block the degradation of a substrate indirectly by promoting the degradation of its E3 ."
25325686
ZUP1 affects stabilization tumor suppressors Ub-dependent
| 1
ZUP1 activates stabilization tumor suppressors Ub-dependent. 1 / 1
| 1
eidos
"DUB inhibition leads to degradation of oncogenes and stabilization of tumor suppressors Ub-dependent degradation is rescued by deubiquitinases ( DUBs ) , proteases that selectively remove Ub from Ub-client conjugates ."
30913483
ZUP1 affects similar smears different buffer lysis protocol
| 1
ZUP1 inhibits similar smears different buffer lysis protocol. 1 / 1
| 1
eidos
"As shown in Figure 1C , second lane from the left and USP2 CD - treated lanes , similar smears from a different buffer and lysis protocol ( Materials and Methods ) are not collapsed by the addition of the DUB ."
32580388
reach
"These results show that PEDV infection suppresses production of IFN-β and provides evidence indicating that the PEDV papain-like protease 2 acts as a viral DUB to interfere with the RIG-I- and STING-mediated signalling pathway."
23596270
ZUP1 leads to the ubiquitination of replication protein. 1 / 1
| 1
reach
"ZUFSP interacts with and modulates ubiquitination of the replication protein A (RPA) complex."
29563501
ZUP1 affects remove polyubiquitins substrates
| 1
ZUP1 activates remove polyubiquitins substrates. 1 / 1
| 1
eidos
"These results may suggest that there exists a threshold of DUB activity required for PRRSV replication , in which the DUB activity may be required to remove polyubiquitins from substrates ."
31561412
ZUP1 affects removal ubiquitin ISG15
| 1
ZUP1 activates removal ubiquitin ISG15. 1 / 1
| 1
eidos
"Structural and functional analyses revealed that the papain-like protease ( PLP ) of severe acute respiratory syndrome coronavirus ( SARS-CoV ) has DUB activity that catalyzes the removal of both ubiquitin and ISG15 from substrates [ 115 ] , [ 116 ] ."
25023063
ZUP1 affects removal processing Ub polyubiquitin chains
| 1
ZUP1 activates removal processing Ub polyubiquitin chains. 1 / 1
| 1
eidos
"Additionally , they are more potent than the abovementioned Leucettamol A ( Fig. 5 ) .424 CC0651 , a small-molecule selective allosteric site inhibitor of the E2 enzyme hCdc34 , can block the ubiquitination and degradation of p27 and then inhibit tumor cell proliferation ( Fig. 5 ) .425 In addition , small-molecule microarray-based screening has also been successfully used to identify the inhibitor of the SUMO E2 enzyme Ubc9 , and a few small-molecule inhibitors have been found.426 Targeting DUB activity As mentioned , ubiquitination is a dynamic and reversible process , and DUBs mediate the removal and processing of Ub or polyubiquitin chains from ubiquitinated proteins ."
32140262
ZUP1 affects regulatory mechanism external internal signals
| 1
ZUP1 activates regulatory mechanism external internal signals. 1 / 1
| 1
eidos
"Overall , the E3 and DUBs provide an on-off switch controlling ubiquitination , enabling a regulatory mechanism by external and internal signals ."
33498196
ZUP1 affects regulation mitophagy
| 1
ZUP1 activates regulation mitophagy. 1 / 1
| 1
eidos
"Besides , other studies identified additional DUBs which may also contribute to the regulation of mitophagy ."
30126257
ZUP1 affects regulation Pol iota ubiquitination
| 1
ZUP1 activates regulation Pol iota ubiquitination. 1 / 1
| 1
eidos
"Results Pol iota is a substrate and interacting partner of USP7 The monoubiquitination of Pol iota is dependent on its ubiquitin-binding motifs ( UBMs ) and their capacity to bind and recruit ubiquitin-laden E2 enzymes.26 ,28 While these domains are major drivers of Pol iota monoubiquitination , we considered whether additional regulation of Pol iota ubiquitination might also be mediated by DUBs ."
33279577
ZUP1 affects recycled free ubiquitin
| 1
ZUP1 activates recycled free ubiquitin. 1 / 1
| 1
eidos
"However , additional reduction of recycled free ubiquitin by DUB inhibition can further enhance the inhibitory effect of proteasome inhibitor ."
18612413
ZUP1 affects proteotoxic stress provoked GSH
| 1
ZUP1 activates proteotoxic stress provoked GSH. 1 / 1
| 1
eidos
"These results suggest that inhibition of DUBs induces proteotoxic stress provoked by GSH depletion and raised the question whether , in BSO-sensitive cell lines , single agent BSO treatment is sufficient to induce high levels of proteotoxic stress ."
30799286
ZUP1 affects proteotoxic ER stress
| 1
ZUP1 inhibits proteotoxic ER stress. 1 / 1
| 1
eidos
"DUB inhibition and GSH depletion induces both proteotoxic and ER stress Since DUBs remove ubiquitin groups from proteins , and an accumulation of ubiquitinated proteins can lead to cell death ( D'Arcy and Linder , 2014 ) , we measured total protein ubiquitination in cells eight hours after single agent or combined treatment with BSO and each of the three DUB inhibitors ."
30799286
ZUP1 affects proteolysis UPS substrate
| 1
ZUP1 activates proteolysis UPS substrate. 1 / 1
| 1
eidos
"Usp7 inhibitors also highlight a counterintuitive principle : that DUB inhibitors can block proteolysis of a UPS substrate , albeit indirectly ."
25325686
ZUP1 affects protein
| 1
ZUP1 activates protein. 1 / 1
| 1
eidos
"The activity of DUBs restores ubiquitinated proteins back to their original forms thereby reversing the effects caused by ubiquitination ."
33136002
ZUP1 affects protein virus-infected cells
| 1
ZUP1 inhibits protein virus-infected cells. 1 / 1
| 1
eidos
"Deubiquitinating function of an avian IBV papain-like protease 1947 Similar to the CoV porcine epidemic diarrhea virus ( PEDV ) [ 28 ] , the DUB activity of IBV also dramatically reduced Ub-conjugated protein levels in virus-infected cells , and the IBV PLP plays an important role in this DUB activity ."
28316013
ZUP1 affects protein targets
| 1
ZUP1 inhibits protein targets. 1 / 1
| 1
eidos
"Most DUBs reduce the degradation of protein targets by protecting them from the proteasome , thereby a high concentration of TGF-beta , promoted by specific DUBs , might lead to tumor occurrence and metastasis ."
33498168
ZUP1 affects proteasome function
| 1
ZUP1 activates proteasome function. 1 / 1
| 1
eidos
"Recently , many USP14 inhibitors , such as b-AP15 ( 36 ) , RA-9 ( 47 ) , and AC17 ( 48 ) , have been found to inhibit proteasome function by blocking DUB activity ."
30962318
ZUP1 affects proteasomal
| 1
ZUP1 activates proteasomal. 1 / 1
| 1
eidos
"Thus , b-AP15 effectively inhibits proteasomal activity by inhibiting the DUBs that process polyubiquitylated proteins prior to their engagement by the proteasome ."
22613766
ZUP1 affects prospects identifying compounds
| 1
ZUP1 inhibits prospects identifying compounds. 1 / 1
| 1
eidos
"Processing of such substrates thus requires the DUB to function in a non-physiological manner , thereby potentially diminishing prospects for identifying compounds that will operate in cellular or therapeutic settings ."
28959952
ZUP1 affects proIL‐1β
| 1
ZUP1 deubiquitinates proIL‐1β. 1 / 1
| 1
reach
"In line with this work, Zhang et al.81 have shown that POH1, a DUB that forms part of the 19S subunit of the proteasome, interacts with and deubiquitinates proIL‐1β by decreasing the K63‐linked polyubiquitin chains, as well as decreasing the efficacy of proIL‐1β cleavage."
31679183
ZUP1 affects pro-apoptotic protein p53
| 1
ZUP1 inhibits pro-apoptotic protein p53. 1 / 1
| 1
eidos
"WP1130 , an inhibitor of DUBs , can suppress the activities of USP9X , USP5 , USP14 and UCH37 , deregulate anti-apoptotic protein MCL-1 and upregulate pro-apoptotic protein p53 ."
33643919
ZUP1 affects patients developing resistance
| 1
ZUP1 activates patients developing resistance. 1 / 1
| 1
eidos
"9 A significant challenge with proteasome-targeted therapeutics is drug resistance leading to relapse and death in the treated patients.6 Recent research has discovered that increased activity of DUBs resulted in MM patients developing a resistance to Bortezomib , while combinational treatment of DUB inhibitors and proteasome inhibitors led to enhanced Bortezomib efficacy.1 , 3 , 10 , 11 This finding coupled with the cost of molecularly-targeted therapeutics , and the potential for severe side effects like peripheral neuropathy , has created an urgent need for more advanced biochemical screening methods for members of the UPS including the proteasome and DUBs ."
32831622
ZUP1 affects own ubiquitination
| 1
ZUP1 inhibits own ubiquitination. 1 / 1
| 1
eidos
"However , whether DUBs can reverse their own ubiquitination and regulate their own protein stability requires further investigation ."
33864866
ZUP1 affects overall buildup ubiquitinated proteins
| 1
ZUP1 inhibits overall buildup ubiquitinated proteins. 1 / 1
| 1
eidos
"Since USP7 targets numerous proteins for deubiquitination , loss of this DUB could lead to an overall buildup of ubiquitinated proteins ."
30799286
ZUP1 affects observed stabilization RdRp
| 1
ZUP1 activates observed stabilization RdRp. 1 / 1
| 1
eidos
"As 140K harbours the papain-like PRO domain , and , noting that the substrate specificity of TYMV PRO defined as ( K / R ) LXG ( G / S / A ) ( Jakubiec et al , 2007 ) overlaps the C-terminal Ub sequence RLRGG , we therefore asked whether , in addition to its endopeptidase activity involved in polyprotein processing , TYMV PRO might also possess a DUB activity that might contribute to the observed stabilization of 66K RdRp ."
22117220
ZUP1 affects nucleolar SUMOylation
| 1
ZUP1 activates nucleolar SUMOylation. 1 / 1
| 1
eidos
"Here , we report that USP36 , a nucleolar deubiquitinating enzyme ( DUB ) , promotes nucleolar SUMOylation ."
33852194
ZUP1 affects nuclear factor kappa-light-chain-enhancer
| 1
ZUP1 activates nuclear factor kappa-light-chain-enhancer. 1 / 1
| 1
reach
"For instance, USP7, a host DUB, prevents degradation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) by deubiquitination from K48 of NF-κB p65 subunit in the TLR (TLR3 and TLR9) pathway to enhance stability of NF-kB, which upregulates the transcription of pro-inflammatory cytokines [29] ."
33922750
ZUP1 affects norovirus infection
| 1
ZUP1 activates norovirus infection. 1 / 1
| 1
eidos
"119 To investigate the relationship between DUBs and virus infection , an inhibitor of DUB , WP1130 ( Figure 5 ) , was evaluated to determine whether DUBs promoted norovirus infection ."
28981632
reach
"In addition, loss of the DUB, USP14, reduced neurotransmitter release and increased surface expression of the GABA R (Jarome et al., 2013)."
34602983
ZUP1 affects neuron-to-neuron propagation human coronavirus OC43
| 1
ZUP1 activates neuron-to-neuron propagation human coronavirus OC43. 1 / 1
| 1
eidos
"Dub e M , Le Coupanec A , Wong AH , Rini JM , Desforges M , Talbot PJ ( 2018 ) Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43 ."
33747891
ZUP1 affects nerve cell death
| 1
ZUP1 activates nerve cell death. 1 / 1
| 1
eidos
"Additionally , impairment in function of 26S proteasome , ubiquitinating enzymes , and DUBs can lead to nerve cell death and the progression of neurodegenerative diseases ."
32455657
ZUP1 affects modulation ubiquitin network
| 1
ZUP1 activates modulation ubiquitin network. 1 / 1
| 1
eidos
"Driven by the hypothesis that additional DUBs may contribute to the modulation of the ubiquitin network by L. pneumophila , we performed bioinformatic analyses of Dot / Icm substrates ( Burstein et al ., 2009 ; Zhu et al ., 2011 ) to identify proteins of potential DUB activity ."
33136002
ZUP1 affects modalities
| 1
ZUP1 activates modalities. 1 / 1
| 1
eidos
"Some DUBs modulate multiple modalities of RCD by regulating various substrates and are powerful regulators of cell fate ."
33919439
ZUP1 affects metabolic process
| 1
ZUP1 inhibits metabolic process. 1 / 1
| 1
reach
"Therefore, DUb may inhibit CRC growth by affecting the metabolism of colorectal cancer.Taken together, as an important finding of the current study, DUb is determined to suppress CRC growth in xenograft mouse models with CRC CT26 cells and human CRC tissues."
35177983
ZUP1 affects mature
| 1
ZUP1 activates mature. 1 / 1
| 1
eidos
"First , as UBLs are often translated as pro-proteins or as linear fusion proteins , DUB activity is required to cleave the C termini of UBLs and generate their mature forms ."
21151032
ZUP1 affects malfunction ubiquitin system
| 1
ZUP1 inhibits malfunction ubiquitin system. 1 / 1
| 1
eidos
"However , dysregulation of the DUBs may induce the malfunction of the ubiquitin system , which could subsequently regulate a serial of oncogenes or tumor suppressor genes ( 21 , 22 ) ."
33718205
ZUP1 affects maintain homeostasis context GSH
| 1
ZUP1 inhibits maintain homeostasis context GSH. 1 / 1
| 1
eidos
"Combined suppression of GCLC and deubiquitinating enzymes ( DUBs ) leads to a high level of proteotoxic stress and results in cell death , suggesting that DUB activity is critical to maintain homeostasis in the context of GSH depletion ."
30799286
ZUP1 inhibits lipid hydroperoxide. 1 / 1
| 1
eidos
"These results suggest that while BSO and DUB inhibition induce lipid peroxides , this does not contribute to the cell death observed ."
30799286
ZUP1 affects ligand
| 1
Ligand binds ZUP1. 1 / 1
| 1
reach
"A full description of our findings, along with X-ray structures of other DUB/ligand complexes, will be the subject of a future publication."
26852935
ZUP1 affects lane left USP2CD-treated lanes
| 1
ZUP1 inhibits lane left USP2CD-treated lanes. 1 / 1
| 1
eidos
"As shown in Figure 1C , second lane from the left and USP2CD-treated lanes , similar smears from a different buffer and lysis protocol ( Materials and Methods ) are not collapsed by the addition of the DUB ."
32580388
ZUP1 affects interleukins
| 1
ZUP1 activates interleukins. 1 / 1
| 1
eidos
"We will now discuss DUBs that induce interleukins , which are listed in Table 2 ."
31208841
ZUP1 affects interferon unknown mechanisms
| 1
ZUP1 inhibits interferon unknown mechanisms. 1 / 1
| 1
eidos
"In addition , African swine fever virus , a large DNA virus , has a DUB that is thought to block the production of interferon by unknown mechanisms ."
| PMC
ZUP1 affects interferon antagonism
| 1
ZUP1 activates interferon antagonism. 1 / 1
| 1
eidos
"Inhibition of DUB activity by mutagenesis did not abrogate interferon antagonism ."
26061460
ZUP1 affects interaction
| 1
ZUP1 inhibits interaction. 1 / 1
| 1
eidos
"The authors proposed that HDAC6 negatively regulates the NLRP3 inflammasome through its interaction with ubiquitinated NLRP3 and independently of its deacetylase activity [ 64 ] and that DUBs would be required to reduce this interaction and hence allow inflammasome activation ."
31679183
ZUP1 affects initial inflammatory subsequent interferon response
| 1
ZUP1 inhibits initial inflammatory subsequent interferon response. 1 / 1
| 1
eidos
"DUB activity is hypothesized to cause dysregulation of both the initial inflammatory and subsequent interferon response ."
33594371
ZUP1 affects inflammatory cytokine
| 1
ZUP1 inhibits inflammatory cytokine. 1 / 1
| 1
eidos
"In addition , because viral DUBs often negatively regulate host innate immunity , it is expected that inactivation of DUB activity should promote the inflammatory cytokine production as reported by several cases [ 12,15,16,19,61 ] ."
31561412
ZUP1 affects inflammasome activation
| 1
ZUP1 activates inflammasome activation. 1 / 1
| 1
eidos
"This study showed that chemical inhibition of USP7 and USP47 blocked inflammasome formation and that although both DUBs contributed to inflammasome activation , its activation was majorly impaired when both USP7 and USP47 were not present ."
31679183
ZUP1 affects induction proteotoxic stress
| 1
ZUP1 inhibits induction proteotoxic stress. 1 / 1
| 1
eidos
"Inhibition of GSH synthesis , in combination with DUB inhibition , led to an accumulation of polyubiquitinated proteins , induction of proteotoxic stress , and cell death ."
30799286
ZUP1 affects immune response
| 1
ZUP1 activates immune response. 1 / 1
| 1
eidos
"Although the specificities and functions of various deubiquitinases have not been fully characterized , some DUBs that modulate the immune response have been identified ."
26061460
ZUP1 affects immediate respiration concomitant membrane potential
| 1
ZUP1 inhibits immediate respiration concomitant membrane potential. 1 / 1
| 1
eidos
"DUb caused an immediate increase in respiration and concomitant decline in membrane potential , suggesting opening of a leak channel in both groups ( Figure 3d ) ."
32674111
ZUP1 affects human cancers
| 1
ZUP1 inhibits human cancers. 1 / 1
| 1
eidos
"In this review , we summarize the biological and molecular functions of BAP1 and explain how the inactivation of this DUB might cause human cancers ."
33462414
ZUP1 affects host antiviral response
| 1
ZUP1 inhibits host antiviral response. 1 / 1
| 1
eidos
"This DUB activity may remove ubiquitins from critical intermediates in the innate immune signaling pathway , thereby suppressing host antiviral response ."
| PMC
ZUP1 affects homogeneity
| 1
ZUP1 activates homogeneity. 1 / 1
| 1
eidos
"In fact , prevention of the current leakage was found to improve the temperature homogeneity over the welding area by Dub e et al. [ 72 ] ."
| PMC
reach
"In addition, loss of the DUB, USP14, reduced neurotransmitter release and increased surface expression of the GABA R (Jarome et al., 2013)."
34602983
ZUP1 affects fusion protein
| 1
ZUP1 activates fusion protein. 1 / 1
| 1
eidos
"The fusion protein has minimal enzymatic activity and is significantly activated upon the cleavage of the ubiquitin-enzyme junction by DUBs ."
19489724
ZUP1 affects functional DUB redundancy
| 1
ZUP1 activates functional DUB redundancy. 1 / 1
| 1
eidos
"Our study suggests that functional DUB redundancy may explain why inhibitors that are effective in destabilizing a protein in one physiological context may fail in another context due to expression of DUBs that are functionally redundant ."
33417828
ZUP1 affects free chains are volatile signals
| 1
ZUP1 inhibits free chains are volatile signals. 1 / 1
| 1
eidos
"One possibility is that these free chains are very volatile signals that can rapidly activate a signaling complex and are subsequently degraded by the DUBs present in the cytosol ."
22964110
ZUP1 affects fluorescent signal
| 1
ZUP1 activates fluorescent signal. 1 / 1
| 1
eidos
"Therefore , DUBs can produce a fluorescent signal by cleaving the ubiquitin C terminus of Ub-PLA2 to give a free amino terminus for catalytically active PLA2 ."
32781716
ZUP1 affects explore innate immune signaling
| 1
ZUP1 activates explore innate immune signaling. 1 / 1
| 1
eidos
"Intriguingly , PLpro was recently shown to have unexpected DUB / delSGylation activities ( 29 , 30 ) , which prompted us to explore its effect on innate immune signaling ."
17761676
ZUP1 activates evasion of host immune response. 1 / 1
| 1
reach
"This study provides the first 35 direct evidence that the DUB activity of a coronaviral protease contributes to innate immune evasion 36 and can profoundly enhance virulence in an animal model."
| DOI
ZUP1 affects entire process
| 1
ZUP1 inhibits entire process. 1 / 1
| 1
eidos
"12 The entire process can be reversed by DUBs ."
| PMC
ZUP1 affects electrophilic warhead
| 1
ZUP1 activates electrophilic warhead. 1 / 1
| 1
eidos
"VME was applied as an electrophilic warhead due to its broad reactivity toward DUBs ."
32953009
ZUP1 affects efficiency viral infection
| 1
ZUP1 activates efficiency viral infection. 1 / 1
| 1
eidos
"We observed that debilitating the DUB activity by mutation of the catalytic Cys783 residue is not lethal but leads to decreased viral infectivity , suggesting that the DUB activity indeed contributes to the efficiency of viral infection ."
22117220
ZUP1 affects efficacy proIL-1b cleavage
| 1
ZUP1 inhibits efficacy proIL-1b cleavage. 1 / 1
| 1
eidos
"In line with this work , Zhang et al. [ 81 ] have shown that POH1 , a DUB that forms part of the 19S subunit of the proteasome , interacts with and deubiquitinates proIL-1b by decreasing the K63-linked polyubiquitin chains , as well as decreasing the efficacy of proIL-1b cleavage ."
31679183
ZUP1 affects dysfunction
| 1
ZUP1 activates dysfunction. 1 / 1
| 1
eidos
"Herein we report a novel mechanism by which cylindromatosis ( CYLD ) , a DUB mediates cardiac pathological remodeling and dysfunction ."
32553594
ZUP1 affects drug
| 1
ZUP1 activates drug. 1 / 1
| 1
reach
"Importantly, this work provides proof of concept that potent and selective DUB inhibitors can be achieved and that structural characterization of chemical leads with their cognate DUB target could accelerate probe and drug discovery programs.Detailed methods are provided in the online version of this paper and include the following: Zhang, X.Y., Varthi, M., Sykes, S.M., Phillips, C., Warzecha, C., Zhu, W., Wyce, A., Thorne, A.W., Berger, S.L., and McMahon, S.B."
29056421
ZUP1 affects domain TYMV such
| 1
ZUP1 inhibits domain TYMV such. 1 / 1
| 1
eidos
"Because of its DUB activity , the PRO domain of TYMV can counteract such degradation and inhibit 66K degradation ( 24 ) ."
32732284
ZUP1 affects discovery DUB
| 1
ZUP1 activates discovery DUB. 1 / 1
| 1
eidos
"Subsequently , the OTU family was found to include DUBs [ 33 , 34 ] , which in turn led to the discovery of the DUB activity in PLP2 ."
| PMC
ZUP1 affects diphosphate(4-)
| 1
ZUP1 deubiquitinates diphosphate(4-). 1 / 1
| 1
reach
"DUB, deubiquitylating enzyme; NAE, NEDD8-activating enzyme; PPi, inorganic pyrophosphate; SAE, SUMO-activating enzyme.Figure 2: a | In the first step of UBL activation, E1s bind ATP and a cognate UBL and catalyse the formation of a UBL carboxy- terminal acyl adenylate."
21151032
ZUP1 affects development therapeutic treatment diseases
| 1
ZUP1 activates development therapeutic treatment diseases. 1 / 1
| 1
eidos
"Therefore , the improved understanding of DUBs will hopefully lead to the development of therapeutic strategies for the treatment of diseases ."
32957626
ZUP1 affects deubiquitylation posttranslational ubiquitylation protein is dynamic process
| 1
ZUP1 inhibits deubiquitylation posttranslational ubiquitylation protein is dynamic process. 1 / 1
| 1
eidos
"USP2 counteracts the endocytic degradation of ErbB2 through deubiquitylation The posttranslational ubiquitylation of substrate protein is a dynamic process that can be reversed by DUBs and several DUB activities have been implicated in the regulation of receptor endocytosis , which prompts us to speculate the involvement of DUB activity during the HSP90 inhibitor-incurred ErbB2 downregulation [ 27 ] ."
32327714
ZUP1 affects deubiquitination of RIG-I
| 1
ZUP1 activates deubiquitination of RIG-I. 1 / 1
| 1
eidos
"Some DUBs that mediate the deubiquitination of RIG-I have also been defined ."
26061460
ZUP1 affects deubiquitination Beclin1
| 1
ZUP1 activates deubiquitination Beclin1. 1 / 1
| 1
eidos
"Furthermore , USP14 , a DUB , was verified to induce deubiquitination of Beclin1 ( ref ."
32820146
ZUP1 affects deubiquitinase enzyme
| 1
ZUP1 inhibits deubiquitinase enzyme. 1 / 1
| 1
reach
"Of the targets shown in Fig. 1, an inhibitor of the deubiquitinase enzyme (DUB), OTUD7B, could specifically activate the non-canonical NFkB pathway."
34458756
reach
"OTUB1 has DUB-like activity with an almost exclusive preference for K48-linked poly-Ubiquitin [7, 13] , suggesting that it may have DUB enzyme activity-dependent and independent functions.The Ubiquitin-like protein ISG15 (Interferon stimulated gene 15) resembles a di-Ubiquitin moiety and mediates an antiviral response to certain viruses."
| PMC
ZUP1 affects defect viral infectivity
| 1
ZUP1 inhibits defect viral infectivity. 1 / 1
| 1
eidos
"We , therefore , reasoned that a decreased efficiency of complementation would reflect a defect in viral infectivity due to the lack of DUB activity ."
22117220
reach
"In addition, because viral DUBs often negatively regulate host innate immunity, it is expected that inactivation of DUB activity should promote the inflammatory cytokine production as reported by several cases [12,15,16,19,61]."
31561412
ZUP1 affects cysteine
| 1
Proteasome binds ZUP1 and cysteine. 1 / 1
| 1
reach
"The first of these ubiquitin ABPs was ubiquitin-nitrile, which allowed the labeling of a proteasome-bound cysteine dependent DUB [36]."
25461387
ZUP1 affects coronavirus pathogenesis mice
| 1
ZUP1 activates coronavirus pathogenesis mice. 1 / 1
| 1
eidos
"Disrupting DUB activity mildly attenuates coronavirus pathogenesis in mice ."
32188728
ZUP1 affects cleave K63-linked polyUb
| 1
ZUP1 activates cleave K63-linked polyUb. 1 / 1
| 1
eidos
"In summary , the UBDs in ZUFSP we have here identified , the ZHA and UBZ , form the distal and the putative proximal Ub binding sites , respectively , to together enable the DUB to selectively cleave K63-linked polyUb ( Figure 5G ) ."
29576527
ZUP1 affects cleavage unconventional linkage
| 1
ZUP1 activates cleavage unconventional linkage. 1 / 1
| 1
eidos
"Some L. pneumophila DUBs can catalyze the cleavage of the unconventional linkage between ubiquitin and substrates ."
32974222
ZUP1 affects cleavage cell lysates peptide uptake intact cells
| 1
ZUP1 activates cleavage cell lysates peptide uptake intact cells. 1 / 1
| 1
eidos
"Both DUB mediated cleavage in cell lysates and peptide uptake in intact cells were mathematically characterized using non-linear regression analysis ."
32831622
ZUP1 affects classify ZUFSP
| 1
ZUP1 activates classify ZUFSP. 1 / 1
| 1
eidos
"Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs , leading us to classify ZUFSP as the seventh DUB family ."
29576527
ZUP1 affects cellular processes human malignancies including DNA response oncogenic signaling cascades drug resistance apoptosis cell cycle immunomodulation invasion migration
| 1
ZUP1 inhibits cellular processes human malignancies including DNA response oncogenic signaling cascades drug resistance apoptosis cell cycle immunomodulation invasion migration. 1 / 1
| 1
eidos
"Apart from deubiquitination , DUBs have been shown to modulate cellular processes in human malignancies including DNA damage response , oncogenic signaling cascades , drug resistance , apoptosis , cell cycle , immunomodulation , and invasion / migration ( Table 2 ) ."
33805973
ZUP1 affects cellular lifetimes
| 1
ZUP1 activates cellular lifetimes. 1 / 1
| 1
eidos
"In proteases such as those of CoV , the DUB activity may also contribute to their cellular lifetimes ."
34019767
ZUP1 affects cellular functions
| 1
ZUP1 activates cellular functions. 1 / 1
| 1
eidos
"The above examples describe pathological conditions that are caused by expression of heterologous DUBs or by mutations of endogenous DUBs , although many other disease states or cellular functions have been shown to be modulated by DUBs ."
19571111
ZUP1 affects cell
| 1
ZUP1 activates cell. 1 / 1
| 1
eidos
"The screens performed in this study surveyed a broad spectrum of perturbations to identify factors that render cancer cells dependent on GSH and demonstrated that inhibition of DUBs impedes cells from tolerating depletion of GSH ."
30799286
ZUP1 affects cell migration
| 1
ZUP1 inhibits cell migration. 1 / 1
| 1
reach
"We found that DUb significantly inhibited the CRC cell migration and invasion inside Boyden Chambers in a dose-dependent manner (Figure 4)."
35177983
ZUP1 affects cell growth
| 1
ZUP1 inhibits cell growth. 1 / 1
| 1
reach
"In addition, DUb inhibits breast cancer cell growth and metastasis by regulating the ROS/p53/BAI1 pathway (Cao et al., 2020)."
35177983
ZUP1 affects cardiac pathological remodeling
| 1
ZUP1 activates cardiac pathological remodeling. 1 / 1
| 1
eidos
"Herein we report a novel mechanism by which cylindromatosis ( CYLD ) , a DUB mediates cardiac pathological remodeling and dysfunction ."
32553594
ZUP1 affects breakdown IkappaBalpha
| 1
ZUP1 activates breakdown IkappaBalpha. 1 / 1
| 1
eidos
"Investigations into 19S proteasome deubiquitinates showed that inhibition of these DUBs prevents the breakdown of IkappaBalpha and leads to the inactivation of NF-kappaB , which suppresses cardiac remodeling ( Hu et al ., 2018 ) ."
33584340
ZUP1 affects bioinformatics analysis
| 1
ZUP1 activates bioinformatics analysis. 1 / 1
| 1
eidos
"Among 90 candidates , ten DUBs ( PSMD14 , TNFAIP3 , JOSD1 , UFD1L , UCK2 , SENP5 , COPS5 , USP5 , USP31 and USP39 ) were found to be significantly increased in HNSCC using bioinformatics analysis ."
33456565
ZUP1 affects bands
| 1
ZUP1 activates bands. 1 / 1
| 1
eidos
"Determination of DUB Selectivity and Potential Off-Targets of the ABP As mentioned before , besides the band corresponding to ABP-labeled UCHL1 , a few other bands appeared on the gel ( Figure 3D ) , but on the basis of the DUB profiling results ( Figure 3C ) , these bands can most likely not be attributed to other DUBs ."
32886496
ZUP1 affects bacterial clearance
| 1
ZUP1 inhibits bacterial clearance. 1 / 1
| 1
eidos
"Nox2-deficient RAW cells showed no induction of total cellular ROS production after DUB inhibition and no reduction in bacterial burden indicating that DUBs restrict Nox2-dependent ROS production and bacterial clearance ."
| PMC
ZUP1 affects bacterial PAMPs
| 1
ZUP1 inhibits bacterial PAMPs. 1 / 1
| 1
eidos
"Tumor suppressor deubiquitinase ( DUB ) , cylindromatosis ( CYLD ) , inhibits TLR2 signaling responsible for the recognition of Gram-positive bacterial PAMPs [ PGN , LTA , MALP-2 ( Mycoplasma-derived lipopeptide 2 ) , and Pam3CSK4 ( a synthetic triacylated lipopeptide recognized by TLR1 / TLR2 heterodimer ] [ 174 ] ."
| PMC
ZUP1 affects apoptosis cancer cells
| 1
ZUP1 inhibits apoptosis cancer cells. 1 / 1
| 1
eidos
"Thus , inhibiting DUBs , such as ubiquitin-specific peptidase 14 ( USP14 ) , may induce apoptosis in cancer cells while conferring low cytotoxicity to normal cells ."
33817501
ZUP1 affects anti-apoptotic protein MCL-1
| 1
ZUP1 activates anti-apoptotic protein MCL-1. 1 / 1
| 1
eidos
"WP1130 , an inhibitor of DUBs , can suppress the activities of USP9X , USP5 , USP14 and UCH37 , deregulate anti-apoptotic protein MCL-1 and upregulate pro-apoptotic protein p53 ."
33643919
ZUP1 affects angiogenesis
| 1
ZUP1 inhibits angiogenesis. 1 / 1
| 1
eidos
"DUb suppresses angiogenesis via the ROS / p53 / BAI1 signaling pathway in vascular endothelial cells [ 105 ] ."
33557229
ZUP1 affects aminoluciferin release be assayed bioluminescence luciferase assay
| 1
ZUP1 activates aminoluciferin release be assayed bioluminescence luciferase assay. 1 / 1
| 1
eidos
"In a similar setup , DUB mediated aminoluciferin release can be assayed in a bioluminescence approach using a luciferase assay ( Orcutt et al. 2012 ) ."
30178261
ZUP1 affects activities of supercomplexes
| 1
ZUP1 activates activities of supercomplexes. 1 / 1
| 1
eidos
"The precise mechanism by which DUb increases the activities of supercomplexes [ 100 ] remains unknown ."
33557229
ZUP1 affects active ubiquitin monomer
| 1
ZUP1 activates active ubiquitin monomer. 1 / 1
| 1
eidos
"DUBs are furthermore required to hydrolyze the ubiquitin precursor and generate the active ubiquitin monomer ."
17653289
ZUP1 affects activation recycling localization numerous regulatory-proteins
| 1
ZUP1 activates activation recycling localization numerous regulatory-proteins. 1 / 1
| 1
eidos
"DUBs contribute to activation / deactivation , recycling and localization of numerous regulatory-proteins , thus playing major roles in diverse cellular-processes ."
26077642
ZUP1 affects accumulation polyubiquitinated proteins
| 1
ZUP1 inhibits accumulation polyubiquitinated proteins. 1 / 1
| 1
eidos
"Inhibition of GSH synthesis , in combination with DUB inhibition , led to an accumulation of polyubiquitinated proteins , induction of proteotoxic stress , and cell death ."
30799286
ZUP1 affects accumulation poly-ubiquitylated proteins cells
| 1
ZUP1 inhibits accumulation poly-ubiquitylated proteins cells. 1 / 1
| 1
eidos
"In addition , this study demonstrated that DUBs inhibitors induced the accumulation of poly-ubiquitylated proteins in cells without directly affecting proteasome activity ."
33925279
ZUP1 affects WDR48
| 1
ZUP1 activates WDR48. 1 / 1
| 1
reach
"Structures of non-selective DUB inhibitors.Structures of USP1/UAF1 inhibitors.Structures of a representative Novartis USP2 inhibitor and the cathepsin K inhibitor dutacatib.Structures of early USP7 inhibitors from Hybrigenics.USP7 IC50 4.2 μM USP7 IC 50 8.0 μM USP7 IC 50 0.42 μM USP47 IC 50 4.3 μM USP47 IC 50 8.7 μM USP47 IC 50 1.Structures of USP7 inhibitors from Progenra.Structures of recent USP7 inhibitors.Structures of USP8 inhibitors from Hybrigenics.Structures of a USP8 binder and two inhibitors of non-DUB cysteine proteases which advanced to clinical trials."
26852935
ZUP1 affects WDR20
| 1
WDR20 binds ZUP1. 1 / 1
| 1
reach
"WDR20 also binds the DUB via the “top” face of its β-propeller but interacts with the bottom of the palm subdomain of USP12 to promote an optimal alignment of the catalytic cleft (Li et al., 2016)."
29302259
ZUP1 affects Virus Replication
| 1
eidos
"Viruses can encode proteins with DUBs activity [ 32,44,74,75 ] that can enhance virus replication by both direct and indirect mechanisms ."
33652634
ZUP1 affects Virus Diseases
| 1
ZUP1 activates Virus Diseases. 1 / 1
| 1
reach
"This suggests that the DUB-negative MERS-CoV is less effective in evading innate immunity and that the resulting early and balanced immune response is important for controlling the infection, while the delay in innate immune induction caused by the DUB function during wt virus infection dysregulates the response, causing more severe, immunopathological symptoms (unpublished data)[85]."
31635238
ZUP1 affects VHL-mediated ubiquitination HIF-1alpha
| 1
ZUP1 inhibits VHL-mediated ubiquitination HIF-1alpha. 1 / 1
| 1
eidos
"USP20 , also known as VHL-interacting deubiquitinating enzyme 2 ( VDU2 ) , was the first DUB reported to reverse the VHL-mediated ubiquitination of HIF-1alpha [ 76 ] ."
33466790
ZUP1 affects Unanchored Ub chains
| 1
ZUP1 activates Unanchored Ub chains. 1 / 1
| 1
eidos
"Unanchored Ub chains can also be produced by DUBs that cleave off ubiquitin chains from substrates targeted to the proteasome ."
| PMC
ZUP1 affects UbV.ME.4
| 1
ZUP1 binds UbV.ME.4. 1 / 1
| 1
reach
"UbV.ME.4 bound with sub-nanomolar affinity to the MERS-CoV DUB by establishing a wide network of hydrophobic packing and hydrogen bond interactions (Fig. 5d)."
30851297
ZUP1 affects UbS2
| 1
ZUP1 binds Phe and UbS2. 1 / 1
| 1
reach
"The SARS virus DUB, PLpro, cleaves K48-poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of UbS2 by utilizing a central Phe residue among other hydrophobic residues42."
32393759
ZUP1 affects USP9X USP5 USP14 UCH37
| 1
ZUP1 activates USP9X USP5 USP14 UCH37. 1 / 1
| 1
eidos
"WP1130 , an inhibitor of DUBs , can suppress the activities of USP9X , USP5 , USP14 and UCH37 , deregulate anti-apoptotic protein MCL-1 and upregulate pro-apoptotic protein p53 ."
33643919
ZUP1 affects USP8
| 1
ZUP1 activates USP8. 1 / 1
| 1
reach
"HBX 90,397, another DUB-specific inhibitor, blocks USP8 activity."
| PMC
ZUP1 affects USP15 IFN signaling pathway
| 1
ZUP1 activates USP15 IFN signaling pathway. 1 / 1
| 1
eidos
"Using reporter assays , we found that blocking the DUB activity by mutagenesis did not completely abrogate the ability of USP15 to inhibit the type I IFN signaling pathway ( Fig. 6 ) ."
26061460
ZUP1 affects USP1
| 1
ZUP1 activates USP1. 1 / 1
| 1
reach
"Structures of non-selective DUB inhibitors.Structures of USP1/UAF1 inhibitors.Structures of a representative Novartis USP2 inhibitor and the cathepsin K inhibitor dutacatib.Structures of early USP7 inhibitors from Hybrigenics.USP7 IC50 4.2 μM USP7 IC 50 8.0 μM USP7 IC 50 0.42 μM USP47 IC 50 4.3 μM USP47 IC 50 8.7 μM USP47 IC 50 1.Structures of USP7 inhibitors from Progenra.Structures of recent USP7 inhibitors.Structures of USP8 inhibitors from Hybrigenics.Structures of a USP8 binder and two inhibitors of non-DUB cysteine proteases which advanced to clinical trials."
26852935
ZUP1 affects UBD
| 1
ZUP1 activates UBD. 1 / 1
| 1
reach
"Also, the ZUFSP helical arm (ZHA) domain orient in such a way that it moves closer to the Ub, this orientation enables the formation of a UBD which is very peculiar to ZUFSP."
33538664
ZUP1 affects TRAF6
| 1
ZUP1 ubiquitinates TRAF6. 1 / 1
| 1
reach
"The DUB activity of Lb was further confirmed through observation of the inhibitory effects of Lb on ubiquitination of RIG-I, TRAF3, TRAF6, and TBK1, which eventually prevents activation of the type I IFN pathway."
26511922
ZUP1 affects TRAF3
| 1
ZUP1 inhibits TRAF3. 1 / 1
| 1
reach
"TRAF3 activation can in turn be negated by DUBA, a DUB specifically binding TRAF3 and deconjugating its K63 chains [32] ."
22964110
ZUP1 affects TP53BP1
| 1
ZUP1 inhibits TP53BP1. 1 / 1
| 1
reach
"USP44, USP17L2/DUB3, USP11, ZUFSP and POH1 loss promotes the excessive spreading of Ub at DSBs and concomitant excessive accumulation of 53BP1 [57–65]."
31769469
ZUP1 affects TP53
| 1
ZUP1 deubiquitinates TP53. 1 / 1
| 1
reach
"We also developed a UbV targeting USP10, a second DUB that deubiquitinates p53, and showed that the UbV promoted export of p53 from the nucleus to the cytoplasm (Zhang, Sartori, et al., 2017)."
30851297
ZUP1 affects TNFRSF10B
| 1
ZUP1 inhibits TNFRSF10B. 1 / 1
| 1
reach
"This study indirectly demonstrated that USP14 and/or UCHL5 partakes in decreasing DR5 expression.MCPIP1 is another DUB that decreases DR5 [79]."
31208841
ZUP1 affects TLR2
| 1
ZUP1 inhibits TLR2. 1 / 1
| 1
eidos
"Tumor suppressor deubiquitinase ( DUB ) , cylindromatosis ( CYLD ) , inhibits TLR2 signaling responsible for the recognition of Gram-positive bacterial PAMPs [ PGN , LTA , MALP-2 ( Mycoplasma-derived lipopeptide 2 ) , and Pam3CSK4 ( a synthetic triacylated lipopeptide recognized by TLR1 / TLR2 heterodimer ] [ 174 ] ."
| PMC
ZUP1 affects TGFB
| 1
ZUP1 inhibits TGFB. 1 / 1
| 1
eidos
"Most DUBs reduce the degradation of protein targets by protecting them from the proteasome , thereby a high concentration of TGF-beta , promoted by specific DUBs , might lead to tumor occurrence and metastasis ."
33498168
ZUP1 affects TBK1
| 1
ZUP1 ubiquitinates TBK1. 1 / 1
| 1
reach
"The DUB activity of Lb was further confirmed through observation of the inhibitory effects of Lb on ubiquitination of RIG-I, TRAF3, TRAF6, and TBK1, which eventually prevents activation of the type I IFN pathway."
26511922
ZUP1 affects Syndrome
| 1
ZUP1 activates Syndrome. 1 / 1
| 1
reach
"A benign tumor syndrome of hair follicles known as cylindromatosis is caused by the mutation of CYLD, a USPfamily DUB named after the disease it causes."
19571111
ZUP1 affects Sun
| 1
ZUP1 inhibits Sun. 1 / 1
| 1
reach
"Additionally, though details remain to be resolved, the murine gammaherpesvirus 68 (MHV68) encoded de-ubiquitination (DUB) enzyme ORF68 was shown to antagonize cytosolic sensing of DNA (Sun et al., 2015) ."
30798991
ZUP1 affects Spontaneous DNA
| 1
ZUP1 inhibits Spontaneous DNA. 1 / 1
| 1
eidos
"ZUFSP Prevents Spontaneous DNA Damage and Promotes Cellular Survival in Response Exogenous DNA Damage ( A ) U2-OS cells were transfected with control ( siCTRL ) or ZUFSP ( siZUFSP ) siRNAs for 72 hr and then lysed and analyzed by immunoblotting with the indicated antibodies ."
29576527
ZUP1 affects SUMO-activating enzyme.Figure 2
| 1
ZUP1 deubiquitinates SUMO-activating enzyme.Figure 2. 1 / 1
| 1
reach
"DUB, deubiquitylating enzyme; NAE, NEDD8-activating enzyme; PPi, inorganic pyrophosphate; SAE, SUMO-activating enzyme.Figure 2: a | In the first step of UBL activation, E1s bind ATP and a cognate UBL and catalyse the formation of a UBL carboxy- terminal acyl adenylate."
21151032
ZUP1 affects SUDS3
| 1
ZUP1 deubiquitinates SUDS3. 1 / 1
| 1
reach
"DUB-3 (also known as USP17) is a cytokine-inducible human DUB that was found to deubiquitinate SDS3 and block proliferation in HeLa cells [93]."
31208841
ZUP1 affects SHMT2
1 |
SHMT2 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
22658674
ZUP1 affects SAE
| 1
ZUP1 deubiquitinates SAE. 1 / 1
| 1
reach
"DUB, deubiquitylating enzyme; NAE, NEDD8-activating enzyme; PPi, inorganic pyrophosphate; SAE, SUMO-activating enzyme.Figure 2: a | In the first step of UBL activation, E1s bind ATP and a cognate UBL and catalyse the formation of a UBL carboxy- terminal acyl adenylate."
21151032
ZUP1 affects S2
| 1
Ubiquitin binds ZUP1 and S2. 1 / 1
| 1
reach
"The SARS virus DUB, PLpro, cleaves K48poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of Ub S2 by utilizing a central Phe residue among other hydrophobic residues 42 ."
32393759
ZUP1 affects S1-S2
| 1
ZUP1 binds S1-S2. 1 / 1
| 1
reach
"To allow monitoring chain-specific proteolysis mediated by S1-S2 interactions on the DUB, diUb-AMC substrates were generated (Flierman et al. 2016) ."
30178261
ZUP1 affects RPS21
1 |
RPS21 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
25416956
ZUP1 affects RPA1
| 1
ZUP1 leads to the ubiquitination of RPA1. 1 / 1
| 1
reach
"More specifically, ZUFSP RNAi enhanced RPA1 ubiquitination after HU treatment, whereas RPA2 ubiquitination was enhanced under basal conditions."
29563501
ZUP1 affects RNF8 RNF168 ubiquitylation
| 1
ZUP1 inhibits RNF8 RNF168 ubiquitylation. 1 / 1
| 1
eidos
"Once localized , this DUB inhibits RNF8 / RNF168 ubiquitylation ."
31164001
ZUP1 affects QPCT
| 1
ZUP1 activates QPCT. 1 / 1
| 1
eidos
"Because other DUbs that promote QC such as Rpn11 , Doa4 and Ubp14 ( Fig 1A ) are also required for degrading folded proteins through non-QC pathways [ S3D Fig in S1 File and 20 , 22 ] , we examined the role of Ubp6 in the degradation of two folded proteins , Stp1 and Deg1-Ura3 ."
32401766
ZUP1 affects Protein Stability
| 1
ZUP1 activates Protein Stability. 1 / 1
| 1
eidos
"USP15 , an important DUB , removes ubiquitin chains from target proteins and promotes protein stability ( Padmanabhan et al ., 2018 ) ."
32671073
ZUP1 affects PolyUb
| 1
ZUP1 binds PolyUb. 1 / 1
| 1
reach
"See also Figure S3.Figure 4: Dissecting PolyUb Binding of ZUFSP (A) DUB assays of ZUFSPcat and ZUFSPMIU-cat with the indicated polyUbs."
29576527
ZUP1 affects Phe
| 1
ZUP1 binds Phe and UbS2. 1 / 1
| 1
reach
"The SARS virus DUB, PLpro, cleaves K48-poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of UbS2 by utilizing a central Phe residue among other hydrophobic residues42."
32393759
ZUP1 activates Pain, Postoperative. 1 / 1
| 1
reach
") injection of A-317567 efficaciously exerted an analgesic effect on complete Freud’s adjuvant-induced inflammatory thermal hyperalgesia and postoperative pain caused by skin incision (Dubé et al., 2005)."
33192609
ZUP1 affects PTEN-PI3K autoregulatory loop50
| 1
ZUP1 activates PTEN-PI3K autoregulatory loop50. 1 / 1
| 1
eidos
"In another study , the FOXO-regulated deubiquitinase ( DUB ) USP11 was identified to mediate a PTEN-PI3K autoregulatory loop50 ."
33659963
ZUP1 affects PRMT5
1 |
PRMT5 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
23455924
ZUP1 affects PLA2
| 1
ZUP1 activates PLA2. 1 / 1
| 1
reach
"Activated free PLA2 then proceeds to cleave its fluorescent-tagged substrate.A complication in all isolated cysteine protease DUB assays is the requirement for adding reducing agents such as dithiothreitol (DTT) to prevent cysteine oxidation and to keep the enzymes viable."
26852935
ZUP1 affects PINK1 Parkin-dependent mitophagy
| 1
ZUP1 inhibits PINK1 Parkin-dependent mitophagy. 1 / 1
| 1
eidos
"In addition , recent studies identified two DUBs that suppress PINK1 / Parkin-dependent mitophagy : USP33 , which acts by removing K6 - , K11 - , K48 - , and K63-linked ubiquitin conjugates on Parkin ; and USP36 , which acts by downregulating ATG14 [ 400,401 ] ."
32235615
ZUP1 affects PEX13
| 1
ZUP1 activates PEX13. 1 / 1
| 1
reach
"Fluorescence polarisation detection could then be utilised to test whether compounds were capable of blocking the DUB-mediated cleavage of Ub-AMC to AMC."
26852935
ZUP1 affects PCNA
| 1
ZUP1 leads to the ubiquitination of PCNA. 1 / 1
| 1
reach
"Remarkably, depletion of OTUB1 restored a pharmacologically disabled DSB response, indicating that targeting the OTUB1-E2 interaction might be an attractive route for the development of agents that bolster DSB repair.Another important example of the role played by DUBs in DNA repair relates to USP1, a DUB that modulates both FANCD2/FANCI and PCNA ubiquitylation [196], [197]."
21056014
ZUP1 affects Oncogenes
| 1
ZUP1 activates Oncogenes. 1 / 1
| 1
eidos
"DUB inhibition leads to degradation of oncogenes and stabilization of tumor suppressors Ub-dependent degradation is rescued by deubiquitinases ( DUBs ) , proteases that selectively remove Ub from Ub-client conjugates ."
30913483
ZUP1 affects OTU
| 1
ZUP1 activates OTU. 1 / 1
| 1
reach
"For CCHFV, it was recently shown that the stable occupancy of the CCHFV-encoded DUB with a Ub variant, blocking OTU DUB activity, blocked viral infection in addition to enhancing host antiviral responses [205]."
33925004
ZUP1 affects Nsp11
| 1
ZUP1 leads to the ubiquitination of mutated Nsp11. 1 / 1
| 1
reach
"As shown in Fig. 6B and C, the DUB activity toward polyubiquitinated IB␣ of the individual Nsp11 mutant directly correlated with the capacity to inhibit NF-B activation."
26342881
ZUP1 affects Nox2-dependent ROS
| 1
ZUP1 inhibits Nox2-dependent ROS. 1 / 1
| 1
eidos
"Nox2-deficient RAW cells showed no induction of total cellular ROS production after DUB inhibition and no reduction in bacterial burden indicating that DUBs restrict Nox2-dependent ROS production and bacterial clearance ."
| PMC
ZUP1 activates Neurodegenerative Diseases. 1 / 1
| 1
eidos
"Additionally , impairment in function of 26S proteasome , ubiquitinating enzymes , and DUBs can lead to nerve cell death and the progression of neurodegenerative diseases ."
32455657
ZUP1 inhibits Neoplasm Metastasis. 1 / 1
| 1
reach
"In addition, DUb inhibits breast cancer cell growth and metastasis by regulating the ROS/p53/BAI1 pathway (Cao et al., 2020)."
35177983
ZUP1 affects NRF2-mediated antioxidant response based canonical target NQO1 GCLC
| 1
ZUP1 inhibits NRF2-mediated antioxidant response based canonical target NQO1 GCLC. 1 / 1
| 1
eidos
"Furthermore , DUB inhibition did not increase ROS levels , nor elicit a strong NRF2-mediated antioxidant response ( based on expression of two canonical target genes NQO1 and GCLC ) ( Figures 4B , 4C and S4B ) ."
30799286
ZUP1 affects NLRP7
| 1
ZUP1 deubiquitinates NLRP7. 1 / 1
| 1
reach
"Bednash et al.75 showed that the DUB STAMPBP (or AMSH) deubiquitinates NLRP7 rescuing this receptor from progressing to lysosome degradation and making it available for the formation of an active inflammasome.NLRC4 inflammasome activation can also be controlled by ubiquitination, although very little is known about how this occurs."
31679183
ZUP1 affects NLRP3
| 1
ZUP1 leads to the ubiquitination of NLRP3. 1 / 1
| 1
reach
"The study also showed that CAPE promotes the ubiquitination of NLRP3 through the inhibition of ROS and increases the level of interaction between NLRP3 and the E3 ligase Cullin 1, whereas it decreases the interaction between NLRP3 and CSN5 (a DUB), which together increases NLRP3 ubiquitination."
| PMC
ZUP1 affects NFKBIA
| 1
ZUP1 leads to the deubiquitination of NFKBIA. 1 / 1
| 1
reach
"The DUB-like SseL factor produced by S. Typhimurium inhibits IkBa ubiquitination in response to the TNF-a cytokine, suggesting that SseL acts directly by removing the K48-linked chains of IkBa (Le Negrate et al., 2008) ."
21111231
ZUP1 affects NFKB1
| 1
ZUP1 inhibits NFKB1. 1 / 1
| 1
reach
"Of the targets shown in Fig. 1, an inhibitor of the deubiquitinase enzyme (DUB), OTUD7B, could specifically activate the non-canonical NFkB pathway."
34458756
ZUP1 affects NF-kappaB activation pathway
| 1
ZUP1 inhibits NF-kappaB activation pathway. 1 / 1
| 1
eidos
"Subsequently , A20 , a DUB , removes the K63-ubiquitin chain from MALT1 and thus downregulates the NF-kappaB activation pathway ( 49 ) ."
33329596
ZUP1 affects NF-jB
| 1
ZUP1 inhibits NF-jB. 1 / 1
| 1
reach
"A second DUB, A20 (also known as tumour necrosis factora-induced protein 3, TNFAIP3) negatively regulates NF-jB signalling."
20073038
ZUP1 affects NEDDylation
| 1
ZUP1 inhibits NEDDylation. 1 / 1
| 1
eidos
"Surprisingly , ubiquitin stress-induced NEDDylation was decreased upon ectopic expression of NEDP1 ; however , other DUBs did not induce a significant reduction in NEDDylation ( Figure 4E ) ."
33665565
ZUP1 affects NEDD8
| 1
ZUP1 deubiquitinates NEDD8. 1 / 1
| 1
reach
"DUB, deubiquitylating enzyme; NAE, NEDD8-activating enzyme; PPi, inorganic pyrophosphate; SAE, SUMO-activating enzyme.Figure 2: a | In the first step of UBL activation, E1s bind ATP and a cognate UBL and catalyse the formation of a UBL carboxy- terminal acyl adenylate."
21151032
ZUP1 affects NAE
| 1
ZUP1 deubiquitinates NAE. 1 / 1
| 1
reach
"DUB, deubiquitylating enzyme; NAE, NEDD8-activating enzyme; PPi, inorganic pyrophosphate; SAE, SUMO-activating enzyme.Figure 2: a | In the first step of UBL activation, E1s bind ATP and a cognate UBL and catalyse the formation of a UBL carboxy- terminal acyl adenylate."
21151032
reach
"Importantly, selective interference of PLpro DUB activity could enable future engineering of replication-competent, DUB-deficient MERS-CoV that could be used to investigate the role of PLpro DUB activity during MERS-CoV infection.Not surprisingly, MERS-CoV PLpro has been identified as a target for small-molecule drug design [159], [165], [166], but the development of MERS-CoV-specific antiviral compounds remains in its early stages."
28625850
ZUP1 affects MHV host innate immune response infection
| 1
ZUP1 activates MHV host innate immune response infection. 1 / 1
| 1
eidos
"Overall , we conclude that DUB activity 281 is indeed a virulence trait , and contributes to the ability of MHV to modulate the host innate 282 immune response to infection ."
| DOI
ZUP1 affects MHV host immune response infection
| 1
ZUP1 activates MHV host immune response infection. 1 / 1
| 1
eidos
"Overall , we conclude that DUB activity is indeed a virulence trait and contributes to the ability of MHV to modulate the host innate immune response to infection ."
32188728
ZUP1 affects MAPK
| 1
ZUP1 inhibits MAPK. 1 / 1
| 1
reach
"The YopJ DUB inhibits NF-kB and mitogen-activated protein kinase (MAPK) pathways, a function ascribed previously to its somewhat promiscuous deubiquitination of critical cellular proteins, such as TRAF2, TRAF6, and IkB."
17145306
ZUP1 affects Leukemia
| 1
ZUP1 inhibits Leukemia. 1 / 1
| 1
reach
"Recent study demonstrated that DUb combined with either EDL-360 or thialysine significantly inhibited the growth of human acute leukemia or glioma (Hosni-Ahmed et al., 2014)."
35177983
ZUP1 affects K63-ub
| 1
ZUP1 activates K63-ub. 1 / 1
| 1
reach
"For example, the DUB enzyme cylindromatosis (CYLD) was shown to directly bind RIG-I and mediate the removal of K63-ub and limit IFN induction [45]."
21949557
ZUP1 affects JNK
| 1
ZUP1 inhibits JNK. 1 / 1
| 1
reach
"Monocyte chemotactic protein-inducing protein 1 (MCPIP1) is a protein, common to human and mouse, with DUB activity toward TRAF2, TRAF3 and TRAF6, thereby inhibiting JNK and NF-κB signaling [53]."
31208841
ZUP1 affects JAK2-V617F protein
| 1
ZUP1 activates JAK2-V617F protein. 1 / 1
| 1
eidos
"JOSD1 interacts with and stabilizes JAK2-V617F , and inactivation of the DUB leads to JAK2-V617F protein degradation by increasing its ubiquitination levels , thereby shortening its protein half-life ."
34326465
ZUP1 affects Imd turnover
| 1
ZUP1 activates Imd turnover. 1 / 1
| 1
eidos
"Pirk controls amyloid fibril stability while DUBs and a yet-to-be identified E3s drive amyloid disassembly , ubiquitin editing and Imd turnover via the proteasome ."
30857831
ZUP1 affects IRF3
| 1
ZUP1 inhibits IRF3. 1 / 1
| 1
reach
"At last, using a constitutively active phosphor-mimetic IRF3, it was recently shown that the DUB activity of PLPro also inhibited IRF3 at a postactivation step [196]."
32201497
ZUP1 affects IKB
| 1
ZUP1 leads to the deubiquitination of IKB. 1 / 1
| 1
reach
"The DUB-like SseL factor produced by S. Typhimurium inhibits IkBα ubiquitination in response to the TNF-α cytokine, suggesting that SseL acts directly by removing the K48-linked chains of IkBα (Le Negrate et al., 2008)."
21111231
ZUP1 affects IFNB
| 1
ZUP1 inhibits IFNB. 1 / 1
| 1
reach
"For example, herpes simplex virus 1 encodes the largest tegument protein, UL36, which acts as a DUB to remove ubiquitin chains from TNF receptor associated factor 3 (TRAF3) and consequently inhibits IFN-b signaling [89 ] ."
26426962
ZUP1 affects IFN-␤
| 1
ZUP1 inhibits IFN-␤. 1 / 1
| 1
reach
"We therefore designed luciferase-based reporter gene assays to establish whether the DUB activity of MERS-CoV PL pro alone suffices to antagonize the IFN-␤ pathway."
25320088
ZUP1 affects IFN-β production
| 1
ZUP1 inhibits IFN-β production. 1 / 1
| 1
reach
"The DUB activity of UL36USP is essential to block IFN-β production."
23986588
ZUP1 affects IFIH1
| 1
ZUP1 deubiquitinates IFIH1. 1 / 1
| 1
reach
"USP3 is also a DUB that deubiquitinates K63-polyUb chain of both RIG-I and MDA5 and suppresses IFN-β activation [25]."
31208841
reach
"ZUFSP Deubiquitylates K63 Linked Polyubiquitin Chains to Promote Genome Stability."
29576528
ZUP1 affects GATA3 stabilization FOXP3-expressing cells
| 1
ZUP1 activates GATA3 stabilization FOXP3-expressing cells. 1 / 1
| 1
eidos
"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 ."
28959952
ZUP1 affects Figure 5G
| 1
ZUP1 activates Figure 5G. 1 / 1
| 1
eidos
"In summary , the UBDs in ZUFSP we have here identified , the ZHA and UBZ , form the distal and the putative proximal Ub binding sites , respectively , to together enable the DUB to selectively cleave K63-linked polyUb ( Figure 5G ) ."
29576527
ZUP1 affects FOXO4
| 1
ZUP1 deubiquitinates FOXO4. 1 / 1
| 1
reach
"Notably, USP7 has been identified as the DUB that deubiquitylates FOXO4 and modulates its transcriptional activity in response to oxidative stress [98], making USP7 a prime controller of oxidative stress responses that are frequent hallmarks of tumours and are often associated with the DDR defects [99]."
23712866
ZUP1 affects FANCI
| 1
ZUP1 leads to the ubiquitination of FANCI. 1 / 1
| 1
reach
"Remarkably, depletion of OTUB1 restored a pharmacologically disabled DSB response, indicating that targeting the OTUB1-E2 interaction might be an attractive route for the development of agents that bolster DSB repair.Another important example of the role played by DUBs in DNA repair relates to USP1, a DUB that modulates both FANCD2/FANCI and PCNA ubiquitylation [196], [197]."
21056014
eidos
"Inhibition of DUB activity by USP7i caused ER stress by causing accumulation of polyubiquitinated proteins in cancer cells and increasing concentrations of intracellular reactive oxygen species ( ROS ) ."
33650720
ZUP1 affects EBNA1
| 1
ZUP1 binds EBNA1. 1 / 1
| 1
reach
"The EBV transactivator EBNA1 binds the Ub-specific-processing protease 7 (USP7), a cellular DUB, and this augments binding of EBNA1 to the viral oriP site."
21847386
ZUP1 affects DDX53
| 1
ZUP1 inhibits DDX53. 1 / 1
| 1
reach
"Our results in this study demonstrates that DUb may be the potential agent for the treatment of CRC through upregulating SIRT2.FIGURE 1: DUb inhibits CRC growth in CT26 xenograft tumor models."
35177983
ZUP1 affects Cys223
| 1
ZUP1 binds BHPTP and Cys223. 1 / 1
| 1
reach
"PRED of the binding between BHPTP and ZUFSP revealed Cys223, Arg408, Met410, Asn460, and Tyr465 as the crucial residues responsible for this interaction."
32744966
ZUP1 affects Curcumin Figure shikoccin increment12-PGJ2 are cytotoxic cellular
| 1
ZUP1 activates Curcumin Figure shikoccin increment12-PGJ2 are cytotoxic cellular. 1 / 1
| 1
eidos
"Curcumin ( 3.19 , Figure 3 .4 ) , shikoccin ( 3.20 ) , and increment12-PGJ2 ( 3.21 ) are cytotoxic compounds whose cellular activity is at least partially due to DUB inhibition [ 86 ] ."
| PMC
ZUP1 affects ChFP
| 1
ZUP1 activates ChFP. 1 / 1
| 1
reach
"As expected, expression of either Dub along with the poly(A)-reporter in parental HCT116 cells markedly increased the ChFP:GFP ratio of the stall reporter (Figure 4A,B)."
32011234
ZUP1 affects Cellular Survival
| 1
ZUP1 activates Cellular Survival. 1 / 1
| 1
eidos
"ZUFSP Prevents Spontaneous DNA Damage and Promotes Cellular Survival in Response Exogenous DNA Damage ( A ) U2-OS cells were transfected with control ( siCTRL ) or ZUFSP ( siZUFSP ) siRNAs for 72 hr and then lysed and analyzed by immunoblotting with the indicated antibodies ."
29576527
ZUP1 affects Cell Line
| 1
ZUP1 inhibits Cell Line. 1 / 1
| 1
eidos
"These results suggest that inhibition of DUBs induces proteotoxic stress provoked by GSH depletion and raised the question whether , in BSO-sensitive cell lines , single agent BSO treatment is sufficient to induce high levels of proteotoxic stress ."
30799286
ZUP1 inhibits Carcinoma, Hepatocellular. 1 / 1
| 1
eidos
"Depending on the substrates , some DUBs may suppress liver cancers while others promote ."
32642281
ZUP1 affects CLN8
1 |
CLN8 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
23142642
ZUP1 affects CFTR ER-associated degradation
| 1
ZUP1 inhibits CFTR ER-associated degradation. 1 / 1
| 1
eidos
"CFTR ubiquitylation at the ER is reversible , and USP19 , an ER membrane tail-anchored de-ubiquitylating enzyme ( DUB ) , has been reported to suppress the CFTR ER-associated degradation ( ERAD ) [ 33 ] ."
32331485
ZUP1 affects CDKN2A
1 |
CDKN2A binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
27229929
ZUP1 affects CCHFV-OTU
| 1
ZUP1 inhibits CCHFV-OTU. 1 / 1
| 1
reach
"Also as expected, CCHFV-OTU is inhibited by specific inhibitors of DUB enzymes corresponding to ubiquitin and ISG15 derivates coupled to aldehyde or vinyl sulfone [15À18]."
| PMC
ZUP1 affects BHPTP
| 1
ZUP1 binds BHPTP and Cys223. 1 / 1
| 1
reach
"PRED of the binding between BHPTP and ZUFSP revealed Cys223, Arg408, Met410, Asn460, and Tyr465 as the crucial residues responsible for this interaction."
32744966
ZUP1 affects Amyloid
| 1
ZUP1 activates Amyloid. 1 / 1
| 1
eidos
"Pirk controls amyloid fibril stability while DUBs and a yet-to-be identified E3s drive amyloid disassembly , ubiquitin editing and Imd turnover via the proteasome ."
30857831
ZUP1 affects ATP
| 1
ATP binds ZUP1. 1 / 1
| 1
reach
"DUB, deubiquitylating enzyme; NAE, NEDD8-activating enzyme; PPi, inorganic pyrophosphate; SAE, SUMO-activating enzyme.Figure 2: a | In the first step of UBL activation, E1s bind ATP and a cognate UBL and catalyse the formation of a UBL carboxy- terminal acyl adenylate."
21151032
reach
"(TIF) S5 Fig. Layouts of the two sides of the active site clefts in the coronavirus USP-like PRO/ DUBs in the same representation as for the OTU DUBs of Fig 8. (A) The SARS CoV PRO/ DUB in free (PDB 2FE8) and diubiquitin-bound (PDB 5E6J) forms."
29117247
WP1130 affects ZUP1
| 1
WP1130 inhibits ZUP1. 1 / 1
| 1
reach
"120 Results showed that WP1130 inhibited a proteasomeassociated DUB known as USP14 and restricted replication of several RNA viruses, including SINV, through the IRE1-dependent decay of viral proteins, which was activated upon inhibition of DUBs."
28981632
Ubv affects ZUP1
| 1
Ubv inhibits ZUP1. 1 / 1
| 1
eidos
"Previously , ubiquitin variants ( Ubv ) have been developed to selectively inhibit DUBs by binding to the S1 pocket ( Zhang et al , 2017 ; Gorelik & Sidhu , 2017 ) ."
| DOI
Ubiquitin affects S2
| 1
Ubiquitin binds ZUP1 and S2. 1 / 1
| 1
reach
"The SARS virus DUB, PLpro, cleaves K48poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of Ub S2 by utilizing a central Phe residue among other hydrophobic residues 42 ."
32393759
UbVS affects ZUP1
| 1
UbVS inhibits ZUP1. 1 / 1
| 1
eidos
"Furthermore , since not all DUBs are inhibited by UbVS , the method may fail to identify substrates of UbVS-insensitive DUBs ."
33417828
UbV.ME.4 affects ZUP1
| 1
ZUP1 binds UbV.ME.4. 1 / 1
| 1
reach
"UbV.ME.4 bound with sub-nanomolar affinity to the MERS-CoV DUB by establishing a wide network of hydrophobic packing and hydrogen bond interactions (Fig. 5d)."
30851297
UbV-CC4 affects ZUP1
| 1
UbV-CC4 bound to OTU inhibits ZUP1. 1 / 1
| 1
reach
"Zhang et al. screened a phage display library of billions of Ub variants (UbVs) and showed that a UbV-CC4 could bind the CCHFV OTU with high levels of affinity and specificity in vitro and selectively blocked the deubiquitinating and deISGylating activities of CCHFV DUB [23]."
34206476
UbS2 affects ZUP1
| 1
ZUP1 binds Phe and UbS2. 1 / 1
| 1
reach
"The SARS virus DUB, PLpro, cleaves K48-poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of UbS2 by utilizing a central Phe residue among other hydrophobic residues42."
32393759
USP9X phosphorylation affects ZUP1
| 1
USP9X phosphorylation activates ZUP1. 1 / 1
| 1
eidos
"Interestingly , USP9X phosphorylation enhances the DUB activity towards ankyrin-G and correlates with spine development48 ."
33483467
USP7i affects ZUP1
| 1
USP7i inhibits ZUP1. 1 / 1
| 1
eidos
"Inhibition of DUB activity by USP7i caused ER stress by causing accumulation of polyubiquitinated proteins in cancer cells and increasing concentrations of intracellular reactive oxygen species ( ROS ) ."
33650720
USP47 affects ZUP1
| 1
USP47 activates ZUP1. 1 / 1
| 1
reach
"Structures of non-selective DUB inhibitors.Structures of USP1/UAF1 inhibitors.Structures of a representative Novartis USP2 inhibitor and the cathepsin K inhibitor dutacatib.Structures of early USP7 inhibitors from Hybrigenics.USP7 IC50 4.2 μM USP7 IC 50 8.0 μM USP7 IC 50 0.42 μM USP47 IC 50 4.3 μM USP47 IC 50 8.7 μM USP47 IC 50 1.Structures of USP7 inhibitors from Progenra.Structures of recent USP7 inhibitors.Structures of USP8 inhibitors from Hybrigenics.Structures of a USP8 binder and two inhibitors of non-DUB cysteine proteases which advanced to clinical trials."
26852935
UL36USP affects ZUP1
| 1
UL36USP inhibits ZUP1. 1 / 1
| 1
reach
"As a result, the level of endogenous IκBα in HFF cells with mutant HSV-1 significantly decreased compared to HFF cells with WT HSV-1, supporting that UL36USP decreases the degradation of IκBα in a DUB activity-dependent manner [49]."
31208841
UCHL5 affects ZUP1
| 1
UCHL5 inhibits ZUP1. 1 / 1
| 1
reach
"This study indirectly demonstrated that USP14 and/or UCHL5 partakes in decreasing DR5 expression.MCPIP1 is another DUB that decreases DR5 [79]."
31208841
UBP10 affects ZUP1
| 1
UBP10 activates ZUP1. 1 / 1
| 1
reach
"Using the similar ligation method, Ub-PCNA probes containing a noncleavable linker were also generated.The availability of the above described Ub-PCNA DUB probes coupled with pulldown and proteomics allowed the identification of yeast DUB, particularly Ubp10, that recognizes monoubiquitinated PCNA at K164 and catalyzes its deubiquitination."
| PMC
UBE2N affects ZUP1
| 1
UBE2N inhibits ZUP1. 1 / 1
| 1
reach
"KD of UBC13 strongly decreases ZUFSP accumulation at damage sites further supporting the role of K63 linked ubiquitin chains in this process [XREF_BIBR]."
30257459
UBD affects ZUP1
| 1
UBD activates ZUP1. 1 / 1
| 1
reach
"Interestingly, OtDUB UBD :ubiquitin interaction strongly promotes DUB activity at high OtDUB concentrations."
32393759
TRIM55 affects ZUP1
| 1
TRIM55 activates ZUP1. 1 / 1
| 1
reach
"Conversely, MuRF2 ubiquitination could be enhancing a de-ubiquitinase (DUB) that prevents proteasome-mediated degradation by this unidentified E3(s)."
26242235
TMPRSS11D affects ZUP1
| 1
TMPRSS11D inhibits ZUP1. 1 / 1
| 1
reach
"Our present work demonstrates that the depletion of the SAGA core module arrests development during mid-oogenesis, while our previous work showed that depletion of the HAT module produced a milder phenotype and the DUB module was not required at all for oogenesis [25] ."
| DOI
SHMT2 affects ZUP1
1 |
SHMT2 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
22658674
S2 affects ZUP1
| 1
Ubiquitin binds ZUP1 and S2. 1 / 1
| 1
reach
"The SARS virus DUB, PLpro, cleaves K48poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of Ub S2 by utilizing a central Phe residue among other hydrophobic residues 42 ."
32393759
S1-S2 affects ZUP1
| 1
ZUP1 binds S1-S2. 1 / 1
| 1
reach
"To allow monitoring chain-specific proteolysis mediated by S1-S2 interactions on the DUB, diUb-AMC substrates were generated (Flierman et al. 2016) ."
30178261
Replacement Glu759 Asn760 alanine affects ZUP1
| 1
Replacement Glu759 Asn760 alanine activates ZUP1. 1 / 1
| 1
eidos
"Replacement of Glu759 or Asn760 by alanine resulted in substantially increased DUB activity compared with the WT enzyme : 137 + / - 7 % and 135 + / - 8 % for E759A and N760A , respectively ( Fig. 3A ) ."
32732284
Replacement Glu Asn alanine affects ZUP1
| 1
Replacement Glu Asn alanine activates ZUP1. 1 / 1
| 1
eidos
"Replacement of Glu 759 or Asn 760 by alanine resulted in substantially increased DUB activity compared with the WT enzyme : 137 6 7 % and 135 6 8 % for E759A and N760A , respectively ( Fig. 3A ) ."
32732284
RPS21 affects ZUP1
1 |
RPS21 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
25416956
RPA affects ZUP1
| 1
RPA binds ZUP1. 1 / 1
| 1
reach
"The DNA dependent binding of ZUFSP to the RPA complex was confirmed by co-immunoprecipitation experiments."
29476094
RA-9 is non-specific affects ZUP1
| 1
RA-9 is non-specific activates ZUP1. 1 / 1
| 1
eidos
"RA-9 is a non-specific inhibitor that irreversibly inhibits DUBs by exposing its carbonyl group to a nucleophilic attack from the SH - group of cysteine ( 11 ) ."
32236606
Proteasome affects cysteine
| 1
Proteasome binds ZUP1 and cysteine. 1 / 1
| 1
reach
"The first of these ubiquitin ABPs was ubiquitin-nitrile, which allowed the labeling of a proteasome-bound cysteine dependent DUB [36]."
25461387
PolyUb affects ZUP1
| 1
ZUP1 binds PolyUb. 1 / 1
| 1
reach
"See also Figure S3.Figure 4: Dissecting PolyUb Binding of ZUFSP (A) DUB assays of ZUFSPcat and ZUFSPMIU-cat with the indicated polyUbs."
29576527
Plant Extracts affects ZUP1
1 |
Plant Extracts increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
23557933
Phe affects ZUP1
| 1
ZUP1 binds Phe and UbS2. 1 / 1
| 1
reach
"The SARS virus DUB, PLpro, cleaves K48-poly-ubiquitin down to di-ubiquitin and also binds the I44 patch of UbS2 by utilizing a central Phe residue among other hydrophobic residues42."
32393759
PTPN1 affects ZUP1
| 1
PTPN1 activates ZUP1. 1 / 1
| 1
reach
"High PTP1B expression can increase Ras activity, thereby increasing the risk of tumorigenesis (Dubé et al., 2004)."
35059399
PRMT5 affects ZUP1
1 |
PRMT5 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
23455924
PLpro’s affects ZUP1
| 1
PLpro’s activates ZUP1. 1 / 1
| 1
reach
"Furthermore, domain exchanges of PLpro’s between different SARS-CoV variants supported this observation, establishing DUB activity to be a distinguishing virulence trait."
30629698
PLpro mutants affects ZUP1
| 1
PLpro mutants inhibits ZUP1. 1 / 1
| 1
reach
"This also resulted in the strongestinhibition by PLpro, providing a maximum window to assess the effectson IFN-β promoter inhibition by the PLpro mutants withspecifically inactivated DUB activity."
25320088
PLPs affects ZUP1
| 1
PLPs activates ZUP1. 1 / 1
| 1
reach
"Since it is known that cellular antiviral pathways include (de)ubiquitination within their regulatory mechanisms [14,15], PLPs are believed to contribute to infection pathogenesis by using their intrinsic DUB and deISGylating activities to antagonize the activation of the host cell innate immune response [5]."
32429099
PLPro affects ZUP1
| 1
PLPro inhibits ZUP1. 1 / 1
| 1
reach
"Similarly, using the structure of MERS-CoV PLPro in complex with Ub as a guide, mutations were introduced into PLPro that specifically disrupted the DUB function without affecting its proteolytic activity."
32201497
OtDUBUBD affects ZUP1
| 1
OtDUBUBD activates ZUP1. 1 / 1
| 1
reach
"Interestingly, OtDUBUBD:ubiquitin interaction strongly promotes DUB activity at high OtDUB concentrations."
32393759
OTUB1 * affects ZUP1
| 1
OTUB1 * activates ZUP1. 1 / 1
| 1
eidos
"In contrast , OTUB1 * , which has been engineered to have increased DUB activity compared with OTUB1 , showed some activity toward autoubiquitinated HECTD1 ( Fig. 5A , OTUB1 * lanes 3-5 versus 2 ; Fig. S2C for His6-HECTD1CD ) ."
| PMC
OTU affects ZUP1
| 1
OTU activates ZUP1. 1 / 1
| 1
reach
"Addition of OTU-specific inhibitor CC.4 blocked DUB activity of both enzymes."
32497085
OCA2 affects ZUP1
| 1
OCA2 activates ZUP1. 1 / 1
| 1
reach
"This activity is mediated by the viral P protein, which has been shown to transcriptionally upregulate the cellular DUB A20, thus leading to the inhibition of NF-κB-dependent IFN induction via the deubiquitination of TRAF6 (Yokota et al., 2008)."
21847386
ZUP1 is modified
1 |
ZUP1 is acetylated on K262. 1 / 1
1 |
hprd
No evidence text available
19608861
Non-structural protein 8b inhibits ZUP1. 1 / 1
| 1
reach
"Most interestingly, we found that the T88G mutation can selectively block the cis-cleavage activity (Figure 5C), without affecting the trans-cleavage activity (Figure 5A) and only partially blocking the DUB activity in either truncated (Figure 4B) or full-length form (Figure 8B)."
31561412
NUP214 affects ZUP1
| 1
NUP214 activates ZUP1. 1 / 1
| 1
reach
"However, it remains to be determined if other structural components of the viral L protein can modulate the DUB and deISGylating activities of the CCHFV-OTU domain during viral replication.The nairovirus proteases have been described in CCHFV, DUB and Nairobi sheep disease (NSD) [5, 6] , but is also found in the sequence of the L protein of the other 34 members of the genus, like Hazara or Ganjam viruses [22] ."
| PMC
Mutating Y267 L269 affects ZUP1
| 1
Mutating Y267 L269 inhibits ZUP1. 1 / 1
| 1
eidos
"Mutating Y267 and L269 to Ala also abolished DUB activity , highlighting the importance of the ZHA and distal Ub binding for catalysis ( Figure 5D ) ."
29576527
Multiple Chronic Conditions activates ZUP1. 1 / 1
| 1
reach
"Binding partners and multi-protein complexes with which DUBs associate modulate DUB activity and substrate specificity."
19489724
MHV protease DUB-ubiquitin binding surface affects ZUP1
| 1
MHV protease DUB-ubiquitin binding surface inhibits ZUP1. 1 / 1
| 1
eidos
"74 Therefore , it was necessary for us to identify residue ( s ) within the MHV protease / DUB-ubiquitin 75 binding surface that can be mutated to result in reduced DUB activity without affecting polyprotein 76 processing ."
| DOI
MAP3K7 affects ZUP1
| 1
MAP3K7 activates ZUP1. 1 / 1
| 1
reach
"The signals transduced by TRAF6 and RIP1 can be discontinued by the OTU DUB A20, which is induced by TAK1 signaling and specifically de-conjugates K63 chains (Figs."
22964110
Lys117 affects ZUP1
| 1
Lys117 activates ZUP1. 1 / 1
| 1
eidos
"ATXN3 is itself regulated by mono-ubiquitination on Lys117 , which enhances DUB activity ( Todi et al. 2009 ) ."
31669734
L86A affects ZUP1
| 1
L86A inhibits ZUP1. 1 / 1
| 1
eidos
"Green : C51A inactivates Lpro 's catalytic activity ; red : I83A or L86A reduce the DUB activity and IFN induction ; pink : L92A and L102A reduce affinity for ISG15 ; orange : C133S reduces affinity for eIF4G ; aquamarine : L143A predicted to open substrate binding pocket ."
32667958
Keywords affects ZUP1
| 1
Keywords activates ZUP1. 1 / 1
| 1
eidos
"Keywords : Otubains , deubiquitylating enzymes , Ubiquitin , Ubiquitin-like proteins , interferon-stimulated genes , Ubiquitin processing enzymes , crystal structure , interferon stimulated genes , ISG15 , DUB , OTU , poly-Ubiquitin chains , signal transduction , protein degradation , protein targeting ."
| PMC
Ile-Leu affects ZUP1
| 1
Ile-Leu activates ZUP1. 1 / 1
| 1
reach
"Recruitment of Cullin E3s is likely to be a more widely used viral strategy of interfering with IFN and cytokine signaling.The interleukin‐2 (IL‐2)‐inducible deubiquitinating enzyme DUB‐2 is induced by IL‐2 stimulation and may regulate IL‐2 signaling."
17145306
IFNB1 affects ZUP1
| 1
IFNB1 activates ZUP1. 1 / 1
| 1
reach
"Mutating the catalytic residue of USP25 was sufficient to block USP25’s effect on IFN-β induction, supporting that IFN-β suppression via USP25 is DUB activity dependent [20]."
31208841
I83A affects ZUP1
| 1
I83A inhibits ZUP1. 1 / 1
| 1
eidos
"Green : C51A inactivates Lpro 's catalytic activity ; red : I83A or L86A reduce the DUB activity and IFN induction ; pink : L92A and L102A reduce affinity for ISG15 ; orange : C133S reduces affinity for eIF4G ; aquamarine : L143A predicted to open substrate binding pocket ."
32667958
I83A L86A affects ZUP1
| 1
I83A L86A inhibits ZUP1. 1 / 1
| 1
eidos
"A mutation in the SAP domain ( I83A / L86A ) , was previously reported to abolish the ability of Lpro to suppress type I IFN expression , to degrade signaling proteins ( i.e. NF-kappaB p65 , IRF3 and IRF7 ) , and to disrupt its DUB activity [ 36,37,39 ] , and was therefore included in our screening ."
32667958
I-IFN affects ZUP1
| 1
I-IFN inhibits ZUP1. 1 / 1
| 1
reach
"[57] [58] [59] Our findings rationalize that similar to HCMV, other DUB-encoding viruses may perturb normal cell cycle or apoptotic pathways by inhibiting I-IFN synthesis."
28981114
Gold complexes affects ZUP1
| 1
Gold complexes inhibits ZUP1. 1 / 1
| 1
eidos
"Gold complexes such as 3.25 potently inhibit DUBs and are endowed with cytotoxic activity [ 95 ] ."
| PMC
GRL-0167 affects ZUP1
| 1
GRL-0167 inhibits ZUP1. 1 / 1
| 1
eidos
"GRL-0167 , hypericin , and rutin , in order , inhibited DUB activity in another study [ 80 ] ."
33669054
Figure affects ZUP1
| 1
Figure inhibits ZUP1. 1 / 1
| 1
eidos
"Treatment of HeLa cells with high concentrations of PR-619 ( 50 muM ) led to reduced intensity in many labeled DUB bands , indicating intracellular inhibition of DUB activity by PR-619 ( Figure 6 ) ."
30240200
EBNA1 affects ZUP1
| 1
ZUP1 binds EBNA1. 1 / 1
| 1
reach
"The EBV transactivator EBNA1 binds the Ub-specific-processing protease 7 (USP7), a cellular DUB, and this augments binding of EBNA1 to the viral oriP site."
21847386
Dienones affects ZUP1
| 1
Dienones inhibits ZUP1. 1 / 1
| 1
eidos
"Dienones have indeed been shown to inhibit DUB and also deSUMOylase activities ."
33146523
DUB-ubiquitin Ub binding surface affects ZUP1
| 1
DUB-ubiquitin Ub binding surface inhibits ZUP1. 1 / 1
| 1
eidos
"Therefore , it was necessary for us to identify residue ( s ) within the MHV protease / DUB-ubiquitin ( Ub ) binding surface that can be mutated to result in reduced DUB activity without affecting polyprotein processing ."
32188728
DUB ABPs affects ZUP1
| 1
DUB ABPs activates ZUP1. 1 / 1
| 1
eidos
"33 The above-mentioned DUB ABPs have greatly enhanced our knowledge of DUBs through elucidation of linkage specificity ,22 -26 structural determination of DUB-Ub cocrystal structures ,34 -39 and the development of DUB inhibitors ."
30240200
D98A affects ZUP1
| 1
D98A inhibits ZUP1. 1 / 1
| 1
eidos
"D96A and D98A abolished the DUB activity , which confirmed the critical interaction with C101 for the catalysis and the regulatory role of the loop of amino acid residue 92-99 , respectively ( Figure 3c ) ."
32216114
D96A affects ZUP1
| 1
D96A inhibits ZUP1. 1 / 1
| 1
eidos
"D96A and D98A abolished the DUB activity , which confirmed the critical interaction with C101 for the catalysis and the regulatory role of the loop of amino acid residue 92-99 , respectively ( Figure 3c ) ."
32216114
Cys223 affects ZUP1
| 1
ZUP1 binds BHPTP and Cys223. 1 / 1
| 1
reach
"PRED of the binding between BHPTP and ZUFSP revealed Cys223, Arg408, Met410, Asn460, and Tyr465 as the crucial residues responsible for this interaction."
32744966
Cys residues SVV 3Cpro affects ZUP1
| 1
Cys residues SVV 3Cpro activates ZUP1. 1 / 1
| 1
eidos
"Therefore , we speculate that the Cys and His residues of SVV 3Cpro may contribute to both protease and DUB activities ."
30408499
Cys oxidation affects ZUP1
| 1
Cys oxidation activates ZUP1. 1 / 1
| 1
eidos
"Recently , three distinct works have shown that Cys oxidation can modulate DUB activity ."
31072419
CLN8 affects ZUP1
1 |
CLN8 binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
23142642
CDKN2A affects ZUP1
1 |
CDKN2A binds ZUP1. 1 / 1
1 |
biogrid
No evidence text available
27229929
BHPTP affects ZUP1
| 1
ZUP1 binds BHPTP and Cys223. 1 / 1
| 1
reach
"PRED of the binding between BHPTP and ZUFSP revealed Cys223, Arg408, Met410, Asn460, and Tyr465 as the crucial residues responsible for this interaction."
32744966
Altering residue mutation R844A Fig. 3A interaction TYMV DUB Ile36 patch affects ZUP1
| 1
Altering residue mutation R844A Fig. 3A interaction TYMV DUB Ile36 patch activates ZUP1. 1 / 1
| 1
eidos
"Altering the central residue ( mutation R844A ; Fig. 3A ) in the interaction of TYMV PRO / DUB with Ub Ile36 patch dramatically improved DUB activity , a result that likely reflects improved Ub binding , as confirmed by molecular dynamics simulations ."
32732284
Altering residue mutation R844A Fig. 3A interaction TYMV DUB Ile patch affects ZUP1
| 1
Altering residue mutation R844A Fig. 3A interaction TYMV DUB Ile patch activates ZUP1. 1 / 1
| 1
eidos
"Altering the central residue ( mutation R844A ; Fig. 3A ) in the interaction of TYMV PRO / DUB with Ub Ile 36 patch dramatically improved DUB activity , a result that likely reflects improved Ub binding , as confirmed by molecular dynamics simulations ."
32732284
ATP affects ZUP1
| 1
ATP binds ZUP1. 1 / 1
| 1
reach
"DUB, deubiquitylating enzyme; NAE, NEDD8-activating enzyme; PPi, inorganic pyrophosphate; SAE, SUMO-activating enzyme.Figure 2: a | In the first step of UBL activation, E1s bind ATP and a cognate UBL and catalyse the formation of a UBL carboxy- terminal acyl adenylate."
21151032
A-317567 affects ZUP1
| 1
A-317567 inhibits ZUP1. 1 / 1
| 1
reach
"In acutely dissociated adult rat DRG neurons, A-317567 was shown to produce a potent blocking of ASIC3 with an IC of 1.025 μM and to equipotently block the sustained phase of the ASIC3-like current, a biphasic current akin to that of cloned ASIC3 (Dubé et al., 2005)."
33192609
3-isobutyl-1-methyl-7H-xanthine increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
28628672
3-bromo-6-{[4-hydroxy-1-3 affects ZUP1
| 1
3-bromo-6-{[4-hydroxy-1-3 activates ZUP1. 1 / 1
| 1
reach
"3-bromo-6-{[4-hydroxy-1-3 (3-phenylbutanoyl) piperidin-4-yl] methyl}-4H,5H,6H,7H-thieno [2,3- C] pyridine-7-one (BHPTP) which is an inhibitor of USP7 was repurposed to target ZUFSP."
32744966
reach
"(TIF) S5 Fig. Layouts of the two sides of the active site clefts in the coronavirus USP-like PRO/ DUBs in the same representation as for the OTU DUBs of Fig 8. (A) The SARS CoV PRO/ DUB in free (PDB 2FE8) and diubiquitin-bound (PDB 5E6J) forms."
29117247
1,2-dithiol-3-thione decreases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
19162173
4,4'-sulfonyldiphenol increases the amount of ZUP1. 1 / 1
1 |
ctd
No evidence text available
28628672