IndraLab
Statements
sparser
"Taken together, our results indicate that the ability of OTUB1 to bind preferentially to the UBC13~Ub conjugate and inhibit ubiquitin transfer is allosterically regulated by free ubiquitin binding to the distal site of OTUB1, which triggers capture of the conjugated ubiquitin in the OTUB1 proximal site."
sparser
"Taken together, our results indicate that the ability of OTUB1 to bind preferentially to the UBC13~Ub conjugate and inhibit ubiquitin transfer is allosterically regulated by free ubiquitin binding to the distal site of OTUB1, which triggers capture of the conjugated ubiquitin in the OTUB1 proximal site."
OTUB1 is modified
2
|
1
93
6
OTUB1 is phosphorylated.
2
|
1
52
6
sparser
"Our findings show that the phosphorylation of OTUB1 at Ser 16 did not impact its catalytic activity and its ability to interact with K63-linked ubiquitin chains as well as the E2 enzyme, UBE2N. Instead, we demonstrated that Ser 16 phosphorylation of OTUB1 was essential for its nuclear accumulation, suggesting that nuclear roles of OTUB1 are likely to be regulated through CK2-mediated phosphorylation of OTUB1."
sparser
"Our findings show that the phosphorylation of OTUB1 at Ser 16 did not impact its catalytic activity and its ability to interact with K63-linked ubiquitin chains as well as the E2 enzyme, UBE2N. Instead, we demonstrated that Ser 16 phosphorylation of OTUB1 was essential for its nuclear accumulation, suggesting that nuclear roles of OTUB1 are likely to be regulated through CK2-mediated phosphorylation of OTUB1."
OTUB1 is hydroxylated.
|
35
sparser
"In order to investigate if the observed OTUB1 N22 hydroxylation was regulated by physiologically relevant changes in the cellular microenvironment, we incubated HEK293 cells overexpressing both OTUB1 and FIH in 0.2% oxygen for 8 h with and without subsequent re-oxygenation at 21% oxygen for one additional hour."
OTUB1 is ubiquitinated.
|
5
OTUB1 is methylated.
|
1
reach
"In order to determine the structural basis for OTUB1 inhibition of E2 enzymes, and how ubiquitin allosterically regulates OTUB1 activity, we determined the structure of Caenorhabditis elegans OTUB1 (ceOTUB1) bound to human UBC13 at 1.8 A resolution (XREF_FIG), and a 2.35 A resolution quaternary complex structure containing ceOTUB1, Ubal and a UBC13 DCA ~ Ub conjugate generated with Ub G76C."
reach
"Resulting changes in substrate ubiquitination or downstream signaling pathways in cells expressing the mutant DUB are generally assumed to be due to the absence of deubiquitinating activity, with the notable exceptions of OTUB1, which inhibits E2 enzymes by a mechanism independent of catalytic activity 15, 16, 17 and OTUD4, which serves as a scaffold for USP enzymes 18."
reach
"To investigate whether the inhibition of E2 by OTUB1 was the rate limiting step in its inhibition of SMAD3 polyubiquitylation in vitro, we set up an in vitro ubiquitylation assay with ubiquitin, E1, varying concentrations of E2, E3 and recombinant human SMAD3 in the presence or absence of 0.5 muM GST-OTUB1 (XREF_FIG)."
reach
"Recently, several studies have described a non canonical mode of OTUB1 action in which OTUB1 inhibits the ubiquitylation of target proteins by binding to and inhibiting the E2 ubiquitin conjugating enzyme UBE2N (also known as UBC13) independent of its catalytic activity XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR."
reach
"Since only uncharged E2 stimulates OTUB1 DUB activity while charged E2 ~ Ub represses OTUB1 under normal cellular concentrations of free ubiquitin, the relative proportion of charged versus uncharged E2s must be critical determinants of whether OTUB1-E2 complexes function as active DUBs in the cell."
reach
"Since only uncharged E2 stimulates OTUB1 DUB activity while charged E2 ~ Ub represses OTUB1 under normal cellular concentrations of free ubiquitin, the relative proportion of charged versus uncharged E2s must be critical determinants of whether OTUB1-E2 complexes function as active DUBs in the cell."
sparser
"CD44 overexpression significantly increased SLC7A11 protein levels and inhibited erastin-induced ferroptosis, but these effects were abrogated in OTUB1 KO cells, suggesting that CD44 regulates SLC7A11 protein stability and ferroptosis through OTUB1 and likely by promoting SLC7A11-OTUB1 interaction."
sparser
"Recent studies have shown that overexpression of CD44 in cancer cells can promote the interaction between OTUB1 and SLC7A11 to enhance the stability of SLC7A11 (a subunit of glutamate-cystine antiporter system Xc-) and thereby inhibiting the ferroptosis, while the partial depletion of CD44 abolished this interaction ( xref )."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
reach
"Moreover, as shown in XREF_SUPPLEMENTARY, co-immunoprecipitation assays revealed that both functional mutants OTUB1 (C91A) and OTUB1 (D88A) can interact with SLC7A11 although the binding affinity between OTUB1 (D88A) and SLC7A11 was apparently lower than the one between OTUB1 (C91A) and SLC7A11."
reach
"Consistent with the role of a DUB in regulating protein stability, OTUB1 overexpression resulted in reduced SLC7A11 ubiquitination and increased SLC7A11 protein half-life and steady protein levels; conversely, OTUB1 deletion in a variety of cancer cell lines resulted in a significant decrease in SLC7A11 protein levels."
reach
"Taken together, although the precise mechanism by which OTUB1 induces SLC7A11 stabilization requires further elucidation, it is very likely that the binding between OTUB1 and SLC7A11 as well as OTUB1 's ability of inhibiting E2 conjugating enzymes recruited by the unknown E3 ligase contribute to SLC7A11 stabilization induced by OTUB1."
reach
"For example, in a non neuronal setting, induction of ferroptosis with the small molecule erastin is suppressed by the ubiquitin ligase NEDD4 [XREF_BIBR], whilst the DUBs OTUB1 and USP7 promote ferroptosis by stabilising the mediators SLC7A11 and p53, respectively [XREF_BIBR, XREF_BIBR]."
reach
"In particular, our results show that (i) OTUB1 is a bona fide binding partner of SLC7A11 both in vitro and in vivo; (ii) OTUB1 acts as a major regulator for SLC7A11 activity in human cancer cells; (iii) OTUB1 inactivation promotes ferroptosis in human cancer cells primarily by down-regulating SLC7A11 levels; (iv) OTUB1 is overexpressed in human cancers and the OTUB1-SLC7A11 interaction is critical for tumor growth; (v) The OTUB1-SLC7A11 interaction is tightly regulated by CD44 in human cancer cells."
sparser
"For example, USP7 modulates the stability of both p53 and MDM2, and maintains the level of p53 ubiquitylation ( xref , xref ); USP2 affects the stability of MDM2 ( xref ); Otub1 inhibits p53 ubiquitination and activates p53 in cells ( xref ); USP10 regulates the location and stability of p53, and stabilize both mutated and wild-type p53, thereby having a dual role in tumorigenesis ( xref )."
reach
"For example, USP7 modulates the stability of both p53 and MDM2, and maintains the level of p53 ubiquitylation; USP2 affects the stability of MDM2; Otub1 inhibits p53 ubiquitination and activates p53 in cells; USP10 regulates the location and stability of p53, and stabilize both mutated and wild-type p53, thereby having a dual role in tumorigenesis."
sparser
"CD44 overexpression significantly increased SLC7A11 protein levels and inhibited erastin-induced ferroptosis, but these effects were abrogated in OTUB1 KO cells, suggesting that CD44 regulates SLC7A11 protein stability and ferroptosis through OTUB1 and likely by promoting SLC7A11-OTUB1 interaction."
sparser
"Recent studies have shown that overexpression of CD44 in cancer cells can promote the interaction between OTUB1 and SLC7A11 to enhance the stability of SLC7A11 (a subunit of glutamate-cystine antiporter system Xc-) and thereby inhibiting the ferroptosis, while the partial depletion of CD44 abolished this interaction ( xref )."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
reach
"Moreover, as shown in XREF_SUPPLEMENTARY, co-immunoprecipitation assays revealed that both functional mutants OTUB1 (C91A) and OTUB1 (D88A) can interact with SLC7A11 although the binding affinity between OTUB1 (D88A) and SLC7A11 was apparently lower than the one between OTUB1 (C91A) and SLC7A11."
reach
"18 In here, we not only show that the potent oncogene FOXM1 is a target of OTUB1 but also present evidence to demonstrate that the oncogenic and genotoxic functions of OTUB1 depend on the expression of a functional FOXM1, suggesting that OTUB1 promotes cell proliferation and epirubicin resistance predominantly through targeting FOXM1."
reach
"Recently, UBE2E1 was shown to autoubiquitinate itself in vitro in the presence or absence of the E3 ligase, RNF4 (30, 31), raising the possibility that OTUB1 may stabilize UBE2E1 by preventing autoubiquitination.To test the hypothesis that OTUB1 may directly inhibit UBE2E1, we assayed the autoubiquitinating activity of UBE2E1 in the presence and absence of OTUB1 in vitro."
"OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination"
reach
"Although it is not known whether RNF4 stimulates UBE2E1 in vivo, our in vitro results raised the interesting possibility that OTUB1 could inhibit UBE2E1 autoubiquitination in cells, thereby accounting for the ability of OTUB1 to prevent UBE2E1 from being targeted to the proteasome."
"We find that OTUB1 depletion dramatically destabilizes the E2-conjugating enzyme UBE2E1 (UBCH6) in both mouse and human OTUB1 knockout cell lines."
reach
"Recently, UBE2E1 was shown to autoubiquitinate itself in vitro in the presence or absence of the E3 ligase, RNF4 (30, 31), raising the possibility that OTUB1 may stabilize UBE2E1 by preventing autoubiquitination.To test the hypothesis that OTUB1 may directly inhibit UBE2E1, we assayed the autoubiquitinating activity of UBE2E1 in the presence and absence of OTUB1 in vitro."
OTUB1 affects cell population proliferation
|
4
27
OTUB1 activates cell population proliferation.
|
4
22
OTUB1 inhibits cell population proliferation.
|
5
reach
"Taken together, our data demonstrate that Otub1, identified as a Tau interacting protein in the Tau interactome mapping, modulates Tau, by increasing Tau seeded Tau aggregation, by formation of a Otub1 induced Tau complex Tau c, and by increasing the concentration of oligomeric Tau forms in primary neurons."
reach
"Resolution was extended by refinement at 3.3 A resolution against the P2 1 X-ray data set to an R factor / R free of 22.1/28.8%, with a doubling of the contents of the asymmetric unit The fold architectures of UbcH5b, OTUB1 and Ub have been described previously and do not deviate significantly in the Ub ~ UbcH5b and OTUB1-Ub complex (see XREF_SUPPLEMENTARY for sequence alignments and secondary structure assignments)."
reach
"Resolution was extended by refinement at 3.3 A resolution against the P2 1 X-ray data set to an R factor / R free of 22.1/28.8%, with a doubling of the contents of the asymmetric unit The fold architectures of UbcH5b, OTUB1 and Ub have been described previously and do not deviate significantly in the Ub ~ UbcH5b and OTUB1-Ub complex (see XREF_SUPPLEMENTARY for sequence alignments and secondary structure assignments)."
reach
"The importance of the OTUB1 N-terminal helix to its ability to be stimulated by UBCH5B, together with the role of these N-terminal residues in forming the proximal ubiquitin binding site of OTUB1 XREF_BIBR, XREF_BIBR, XREF_BIBR, suggested that UBCH5B may increase OTUB1 affinity for Lys48 diubiquitin via the proximal ubiquitin binding site."
reach
"However, assays of OTUB1 stimulation by UBCH5B or UBCH5B ~ Ub over a range of ubiquitin concentrations (XREF_FIG) (XREF_SUPPLEMENTARY) showed that stimulation by UBCH5B is relatively insensitive to free ubiquitin, but that stimulation by UBCH5B ~ Ub decreases as a function of increasing concentration of free ubiquitin, dropping to low levels below ~ 1 microM free ubiquitin."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
OTUB1 affects Neoplasm Invasiveness
|
1
23
OTUB1 activates Neoplasm Invasiveness.
|
1
22
OTUB1 activates Neoplasm Invasiveness. 10 / 23
|
1
22
reach
"A growing body of literature demonstrates that the DUB Otubain 1 (OTUB1) regulates many cancer associated signaling pathways including MAPK, ERa, epithelial-mesenchymal transition (EMT), RHOa, mTORC1, FOXM1 and P53 to promote tumor cell survival, proliferation, invasiveness and therapeutic resistance."
OTUB1 inhibits Neoplasm Invasiveness.
|
1
OTUB1 inhibits Neoplasm Invasiveness. 1 / 1
|
1
OTUB1 affects apoptotic process
|
1
14
OTUB1 activates apoptotic process.
|
11
OTUB1 inhibits apoptotic process.
|
1
3
OTUB1 inhibits apoptotic process. 4 / 5
|
1
3
reach
"Combined in vivo and in vitro experiments comprising mice lacking OTUB1 specifically in liver parenchymal cells (OTUB1 LPC-KO) and human OTUB1 deficient HepG2 cells revealed that OTUB1 prevented hepatocyte necroptosis but not apoptosis upon infection with Lm and DGal and TNF challenge."
eidos
"Combined in vivo and in vitro experiments comprising mice lacking OTUB1 specifically in liver parenchymal cells ( OTUB1 LPC-KO ) and human OTUB1-deficient HepG2 cells revealed that OTUB1 prevented hepatocyte necroptosis but not apoptosis upon infection with Lm and DGal / TNF challenge ."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"In order to explore this concept, we performed a c-Maf-recognition element-driven luciferase-based screen against FDA-approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
reach
"In order to explore this concept, we performed a c-Maf-recognition element driven luciferase based screen against FDA approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
reach
"It is essential for Otub1 to engage with c-Maf before preventing c-Maf polyubiquitination and degradation via the ubiquitin-proteasomal pathway, however, AVT can disrupt this interaction between Otub1 and c-Maf, which further abolishes the deubiquitinating activity of Otub1 towards c-Maf."
reach
"On the other hand, the lack of effect of high OTUB1 expression levels on patients ' survival could be further explained by the alternative interactions of OTUB1 beyond RAS that for instance were reported to lead to the stabilization of p53 (Sun etal, 2012) or CK2 mediated OTUB1 nuclear translocation to affect DNA repair (Herhaus etal, 2015)."
reach
"In contrast, OTU domain, ubiquitin aldehyde binding 1 (OTUB1), B-cell lymphoma-3 (BCL-3), ubiquitin carboxyl-terminal hydrolase 1 (UCHL1), and UCHL5 contribute to the deubiquitination of SMAD2 or SMAD3, making them more stable and less easily degradable and promoting TGF-beta signaling [XREF_BIBR - XREF_BIBR]."
OTUB1 affects Neoplasm Metastasis
|
13
reach
"Stimulation of OTUB1-competent BMDCs with both TgPFN and LPS resulted in increased p38, ERK1/2, and JNK phosphorylation compared to that in OTUB1-deficient BMDCs (Supplementary Fig. 2g, h), demonstrating that OTUB1 augments the activation of both NF-κB and MAPKs upon the engagement of TLR4 and TLR11/12."
reach
"OTUB1 overexpression in the H1993 cell line harboring wt KRAS led to a higher and more sustained activation of ERK1/2 phosphorylation (Fig XREF_FIG A), whereas the introduction of OTUB1 into KRAS-mutant A549 cells only slightly increased the activity of the MAPK pathway (Fig XREF_FIG B)."
reach
"Consistently with our observation that OTUB1 overexpression induces the MAPK cascade activation in cells with wt RAS, we found that higher levels of OTUB1 significantly correlated with increased levels of ERK1/2 phosphorylation in lung adenocarcinomas harboring wt KRAS (Pearson 's coefficient : 0.352; P-value : 0.013) (Fig XREF_FIG D and E), while mutant KRAS tumors exhibited in general higher levels of ERK1/2 phosphorylation (Fig XREF_FIG D and E)."
OTUB1 affects Endometriosis
|
13
sparser
"In the absence of a structure of OTUB1 bound to Lys48 diubiquitin and E2, we took advantage of the observation that the two ubiquitins bound to the proximal and distal sites of OTUB1 mimic the binding of Lys48 diubiquitin xref , xref to examine the structural effect of E2 binding on the N-terminal ubiquitin binding helix of OTUB1."
sparser
"In particular, it was shown that FAT10 binding to either wild-type OTUB1 or the enzymatically inactive C91S variant of OTUB1 downregulated the poly-ubiquitylation of TRAF3 in cells, and this effect was especially prominent for ubiquitin chains linked via the lysine residue 63 of ubiquitin (K63) [ xref ]."
reach
"Importantly, all of these values are up to almost an order of magnitude lower than the K d of each E2 for OTUB1 in the absence of diubiquitin, highlighting the potential for K48 polyubiquitin chains to drive association of OTUB1 with its E2 partners at E2 concentrations on the order of 1 muM or less (XREF_FIG)."
reach
"Indeed, the ability of OTUB1 to inhibit RNF168 dependent ubiquitylation is independent of its catalytic activity, and is instead mediated by its binding to and inhibition of the E2 UBC13, which cooperates with RNF168, suggesting that E2 regulation could also represent a means to regulate the DDR pathway."
sparser
"In order to explore this concept, we performed a c-Maf-recognition element-driven luciferase-based screen against FDA-approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
reach
"In order to explore this concept, we performed a c-Maf-recognition element driven luciferase based screen against FDA approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
reach
"It is essential for Otub1 to engage with c-Maf before preventing c-Maf polyubiquitination and degradation via the ubiquitin-proteasomal pathway, however, AVT can disrupt this interaction between Otub1 and c-Maf, which further abolishes the deubiquitinating activity of Otub1 towards c-Maf."
MiR-542-3p affects OTUB1
|
11
MiR-542-3p decreases the amount of OTUB1.
|
4
reach
"For example, miR-542-3p expressions are greatly down-regulated in esophageal cancer, and miR-542-3p can inhibit the migration and aggressiveness of esophageal cancer cells by inhibiting OTUB1 expression [17]; in osteosarcoma, miR-542-3p can curb cell proliferative, migrative and aggressive abilities via targeting ILK [18]; in ovarian cancer, miR-542-3p can target CDK14 to inhibit tumorigenesis [19]; in bladder cancer, importantly, miR-542-3p expression is significantly impaired, and this miRNA can inhibit the viability of BC cells [20]."
MiR-542-3p inhibits OTUB1.
|
3
MiR-542-3p increases the amount of OTUB1.
|
2
MiR-542-3p binds OTUB1.
|
2
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
OTUB1 affects Prostatic Neoplasms
|
11
OTUB1 activates Prostatic Neoplasms. 10 / 11
|
11
eidos
"Although we have found that otub1 promoted the proliferation and progression of PCa via mediating and stabling Cyclin E1 , in which one ubiquitination enzyme directly causing to the ubiquitination degradation of Cyclin E1 remains unclear , and the manner of OTUB1 regulating the expression of Cyclin E1 directly or indirectly are still yet not determined ."
OTUB1 affects ubiquitination
|
8
sparser
"In the absence of a structure of OTUB1 bound to Lys48 diubiquitin and E2, we took advantage of the observation that the two ubiquitins bound to the proximal and distal sites of OTUB1 mimic the binding of Lys48 diubiquitin xref , xref to examine the structural effect of E2 binding on the N-terminal ubiquitin binding helix of OTUB1."
sparser
"In particular, it was shown that FAT10 binding to either wild-type OTUB1 or the enzymatically inactive C91S variant of OTUB1 downregulated the poly-ubiquitylation of TRAF3 in cells, and this effect was especially prominent for ubiquitin chains linked via the lysine residue 63 of ubiquitin (K63) [ xref ]."
eidos
"PKP3 upregulates OTUB1 expression by increasing OTUB1 mRNA stability To test whether PKP3-mediated OTUB1 upregulation is posttranscriptional or transcriptional , we constructed and transfected a luciferase reporter plasmid containing a promoter fragment of OTUB1 into NSCLC cells stably overexpressing PKP3 ."
OTUB1 affects ubiquitylation
|
7
sparser
"Recently, several studies have described a non-canonical mode of OTUB1 action in which OTUB1 inhibits the ubiquitylation of target proteins by binding to and inhibiting the E2 ubiquitin-conjugating enzyme UBE2N (also known as UBC13) independent of its catalytic activity xref xref xref xref ."
reach
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity independent non canonical mechanism."
sparser
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity-independent non-canonical mechanism."
eidos
"All cell lysates were subjected to WB assays as indicated AVT interferes with the interaction between Otub1 and c-Maf to increase c-Maf polyubiquitination AVT was identified from the Otub1 / c-Maf system , while Otub1 interacts with c-Maf and prevents its polyubiquitination as its deubiquitinase , therefore , we wondered whether AVT can inhibit Otub1 activity toward c-Maf ubiquitination ."
sparser
"Negative staining EM shows that one molecule of OTU1 binds to one VCP hexamer, and isothermal titration calorimetry suggests that the two proteins bind with a KD of 0.71 μM. Analytical size exclusion chromatography and isothermal titration calorimetry demonstrates that OTU1 can bind VCP in both the presence and absence of a heterodimer formed by ubiquitin fusion degradation protein 1 and nuclear localization protein 4."
sparser
"Next, Kaplan-Meier's survival analysis was performed to examine the expression of five deubiquitinating enzymes in 117 NSCLC patients (GEO Submission: GSE13213) and revealed that the higher expression of OTUB1 and OTUB2 was significantly associated with poor patient prognosis (Figure xref B-EandFigure xref E)."
sparser
"OTU1 and OTU2 ( R. radiotolerans ) associated to the meteorites ( p = 0.034), as did OTU5 ( Blastococcus sp.) p = 0.034, OTU6 ( G. pulveris ) p = 0.034, OTU12 (Chloroflexi) p = 0.028, OTU15 ( B. jejuensis ) p = 0.034, OTU19 (Frankiales) p = 0.034, OTU21 ( D. navajonensis ) p = 0.034, and OTU23 ( Rubrobacter sp.) p = 0.032."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
OTUB1 affects glycolytic process
|
3
4
|
1
6
sparser
"Negative staining EM shows that one molecule of OTU1 binds to one VCP hexamer, and isothermal titration calorimetry suggests that the two proteins bind with a KD of 0.71 μM. Analytical size exclusion chromatography and isothermal titration calorimetry demonstrates that OTU1 can bind VCP in both the presence and absence of a heterodimer formed by ubiquitin fusion degradation protein 1 and nuclear localization protein 4."
sparser
"Next, Kaplan-Meier's survival analysis was performed to examine the expression of five deubiquitinating enzymes in 117 NSCLC patients (GEO Submission: GSE13213) and revealed that the higher expression of OTUB1 and OTUB2 was significantly associated with poor patient prognosis (Figure xref B-EandFigure xref E)."
sparser
"OTU1 and OTU2 ( R. radiotolerans ) associated to the meteorites ( p = 0.034), as did OTU5 ( Blastococcus sp.) p = 0.034, OTU6 ( G. pulveris ) p = 0.034, OTU12 (Chloroflexi) p = 0.028, OTU15 ( B. jejuensis ) p = 0.034, OTU19 (Frankiales) p = 0.034, OTU21 ( D. navajonensis ) p = 0.034, and OTU23 ( Rubrobacter sp.) p = 0.032."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
sparser
"We demonstrate that E2F1 activates the transcription of TMPO-AS1, which, in turn, facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), a deubiquitinase; consequently, the E2F1 protein levels are increased via stabilization, promoting BC malignant phenotypes."
sparser
"IL-15-stimulated AKT activation is negatively regulated by Otub1, which physically interacts with AKT and prevents its K63 ubiquitination and membrane translocation. xref Interestingly, in IL-15-exposed cells, Otub1 is relocated to the membrane compartment, a mechanism that enables Otub1 to inhibit AKT ubiquitination and activation induced by both IL-15 and TCR signals (Fig. xref )."
OTUB1 affects 4'-epidoxorubicin
|
6
OTUB1 activates 4'-epidoxorubicin. 6 / 6
|
6
reach
"18 In here, we not only show that the potent oncogene FOXM1 is a target of OTUB1 but also present evidence to demonstrate that the oncogenic and genotoxic functions of OTUB1 depend on the expression of a functional FOXM1, suggesting that OTUB1 promotes cell proliferation and epirubicin resistance predominantly through targeting FOXM1."
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
sparser
"We demonstrate that E2F1 activates the transcription of TMPO-AS1, which, in turn, facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), a deubiquitinase; consequently, the E2F1 protein levels are increased via stabilization, promoting BC malignant phenotypes."
reach
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity independent non canonical mechanism."
sparser
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity-independent non-canonical mechanism."
sparser
"These E2 enzymes have EC 50 values in the single digit micromolar range and lower the K M of OTUB1 for its substrate to 6.6 – 14 μM. Since the concentration of UBE2D3 alone has been reported to be 1.7 μM in MEF cells xref and the effective concentration of UBE2D3 needed to stimulate the DUB activity of OTUB1 is 1.6 μM ( xref ), it is likely that OTUB1:UBE2D3 form a stimulated DUB complex in cells."
OTUB1 affects necroptotic process
|
2
3
OTUB1 inhibits necroptotic process. 5 / 5
|
2
3
reach
"Combined in vivo and in vitro experiments comprising mice lacking OTUB1 specifically in liver parenchymal cells (OTUB1 LPC-KO) and human OTUB1 deficient HepG2 cells revealed that OTUB1 prevented hepatocyte necroptosis but not apoptosis upon infection with Lm and DGal and TNF challenge."
OTUB1 affects interleukin-12 production
|
5
OTUB1 activates interleukin-12 production.
|
4
OTUB1 activates interleukin-12 production. 4 / 4
|
4
reach
"Reduced phosphorylation of TAK1, IκBα, and p65 was detected in OTUB1-deficient BMDCs upon stimulation with TgPFN (Fig. 2g), suggesting that OTUB1 is required for the full-fledged activation of NF-κB. To reinforce the assertion that OTUB1 promotes IL-12 production by increasing NF-κB activity, we studied the effect of IKK inhibition on TgPFN-induced cytokine production in OTUB1-sufficient and OTUB1-deficient BMDCs."
OTUB1 inhibits interleukin-12 production.
|
1
OTUB1 inhibits interleukin-12 production. 1 / 1
|
1
sparser
"These E2 enzymes have EC 50 values in the single digit micromolar range and lower the K M of OTUB1 for its substrate to 6.6 – 14 μM. Since the concentration of UBE2D3 alone has been reported to be 1.7 μM in MEF cells xref and the effective concentration of UBE2D3 needed to stimulate the DUB activity of OTUB1 is 1.6 μM ( xref ), it is likely that OTUB1:UBE2D3 form a stimulated DUB complex in cells."
OTUB1 affects MSH2 ubiquitination
|
5
reach
"NS1 is the most important IFNs antagonist protein via mechanisms including inhibition of the TRIM25 mediated RIG-I ubiquitination, suppression of protein kinase R (PKR), phosphorylation of IkappaB kinases (IKK) alpha and beta in the NF-kappaB pathway, interruption of the phosphorylation of STAT1, STAT2, and STAT3 [XREF_BIBR, XREF_BIBR], and degradation of OTUB1 [XREF_BIBR]."
reach
"NS1 is the most important IFNs antagonist protein via mechanisms including inhibition of the TRIM25-mediated RIG-I ubiquitination, suppression of protein kinase R (PKR), phosphorylation of IκB kinases (IKK) α and β in the NF-κB pathway, interruption of the phosphorylation of STAT1, STAT2, and STAT3 [39, 115] , and degradation of OTUB1 [138] ."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63-linked polyubiquitin chains. [172] Because various components are involved in virusinduced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS-mediated but not TBK1-and IRF3-mediated signaling."
OTUB1 affects Cell Survival
|
2
3
OTUB1 activates Cell Survival. 5 / 5
|
2
3
reach
"A growing body of literature demonstrates that the DUB Otubain 1 (OTUB1) regulates many cancer associated signaling pathways including MAPK, ERa, epithelial-mesenchymal transition (EMT), RHOa, mTORC1, FOXM1 and P53 to promote tumor cell survival, proliferation, invasiveness and therapeutic resistance."
sparser
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment ( xref – xref )."
reach
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment (Figure 3h–3i)."
sparser
"Having identified NJH-2-057 as a DUBTAC that was capable of stabilizing mutant CFTR in cells, we next sought to confirm the formation of a ternary complex between CFTR, NJH-2-057, and OTUB1 in vitro using recombinant protein and native mass spectrometry (MS)-based approaches ( xref – xref )."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
FIH affects OTUB1
|
5
sparser
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment ( xref – xref )."
reach
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment (Figure 3h–3i)."
sparser
"Having identified NJH-2-057 as a DUBTAC that was capable of stabilizing mutant CFTR in cells, we next sought to confirm the formation of a ternary complex between CFTR, NJH-2-057, and OTUB1 in vitro using recombinant protein and native mass spectrometry (MS)-based approaches ( xref – xref )."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
Valproic acid affects OTUB1
4
|
OTUB1 affects development endometriosis
|
4
reach
"These data suggest that OTU1 negatively regulates expression of DA1 and DA2 and that its loss of function results in transcriptional activation of these target genes.DA1, a ubiquitin-binding protein, and DA2, a RING-type E3 ubiquitin ligase, are known to interact with each other and negatively regulate the seed and organ size in Arabidopsis (Du et al., 2014, Li and Li, 2014, Li and Li, 2016, Xia et al., 2013)."
OTUB1 affects HSF1 protein stability
|
4
OTUB1 affects Carcinogenesis
|
1
1
reach
"Subsequent experiments further suggested that OTUB1 promoted CRC malignancy by enhancing protein stability of β-catenin, via inhibition of its protein degradation by UPP pathway, which indicated its crucial role in enhancement of CRC tumor cellular proliferative and chemo-resistant capabilities."
OTUB1 affects 17beta-estradiol
|
4
OTUB1 inhibits 17beta-estradiol.
|
3
OTUB1 binds 17beta-estradiol.
|
1
17beta-estradiol binds OTUB1. 1 / 1
|
1
EN523 affects OTUB1
|
4
sparser
"IL-15-stimulated AKT activation is negatively regulated by Otub1, which physically interacts with AKT and prevents its K63 ubiquitination and membrane translocation. xref Interestingly, in IL-15-exposed cells, Otub1 is relocated to the membrane compartment, a mechanism that enables Otub1 to inhibit AKT ubiquitination and activation induced by both IL-15 and TCR signals (Fig. xref )."
Phospho-SMAD2/3 affects OTUB1
|
3
Ubv.B1.1 affects OTUB1
|
3
sparser
"Of the 120 SRP-OTUs, the majority (> 75%) were found to be lake-specific, as they were observed in high relative abundance in only single lake, and only two SRP-OTUs (SRP-OTU1 affiliated with Halomonas ) and (SRP-OTU8 affiliated with Shewanlla ) were present in high relative abundance in all lakes."
sparser
"We unexpectedly find that OTUB1 binding to UBC13∼Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13∼Ub, while at the same time disrupting interactions with UEV1A in a manner that depends on the OTUB1 N terminus."
sparser
"We unexpectedly find that OTUB1 binding to UBC13~Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13~Ub, while at the same time disrupting interactions with UEV1a in a manner that depends upon the OTUB1 N-terminus."
TMPO-AS1 affects OTUB1
|
3
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
OTUB1 affects ubiquitination FOXM1
|
3
OTUB1 affects polyubiquitin chains
|
3
OTUB1 affects phospho-SMAD2/3
|
3
OTUB1 affects cytokine production
|
3
OTUB1 activates cytokine production. 3 / 3
|
3
reach
"In addition, engagement of TLR2, TLR7, and TLR9, which all signal via MyD88, and TLR3, which signals in a MyD88-independent manner through TRIF, resulted in significantly reduced IL-12, TNF, and IL-6 production by OTUB1-deficient BMDCs (Supplementary Fig. 2c), illustrating the stimulatory role of OTUB1 in proinflammatory TLR signaling.To understand how OTUB1 promotes cytokine production in DCs, we stimulated FLT3L-expanded BMDCs with TLA (Fig. 2c), TgPFN (Fig. 2d), and LPS (Fig. 2e) and analyzed signaling molecules by WB analysis."
OTUB1 affects cell death
|
1
1
OTUB1 inhibits cell death.
|
1
OTUB1 inhibits cell death. 1 / 2
|
1
OTUB1 activates cell death.
|
1
OTUB1 activates cell death. 1 / 1
|
1
OTUB1 affects Ubv.B1.1
|
3
sparser
"Of the 120 SRP-OTUs, the majority (> 75%) were found to be lake-specific, as they were observed in high relative abundance in only single lake, and only two SRP-OTUs (SRP-OTU1 affiliated with Halomonas ) and (SRP-OTU8 affiliated with Shewanlla ) were present in high relative abundance in all lakes."
OTUB1 affects UBE2E1 autoubiquitination
|
3
OTUB1 affects TMPO-AS1
|
3
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
eidos
"Subsequent experiments further suggested that OTUB1 promoted CRC malignancy by enhancing protein stability of beta-catenin , via inhibition of its protein degradation by UPP pathway , which indicated its crucial role in enhancement of CRC tumor cellular proliferative and chemo-resistant capabilities ."
eidos
"OTUB1 promotes tumor progression in two ways : to stabilize the expression of oncogenic genes by inhibiting the ubiquitination of target protein , and the other mode does not depend on the deproteinization manner ( Saldana et al ., 2019 ) but directly interacts with E2 ubiquitin ligase ."
reach
"Since OTUB1-competent BMDCs showed stronger activation of TAK1 and production of the cytokines IL-12, TNF, and IL-6 upon engagement of TLR2, TLR7, TLR9, and IL-1R, all of which signal via MyD88, and upon TNF stimulation and poly I:C-induced TLR3 activation, both of which induce MyD88-independent signaling, OTUB1 may contribute to proinflammatory DC responses in a wide range of infections and inflammatory disorders."
OTUB1 affects K48-Ub 2
|
3
|
2
1
OTUB1 affects DNA damage checkpoint
|
3
OTUB1 affects DNA Breaks, Double-Stranded
|
3
OTUB1 inhibits DNA Breaks, Double-Stranded. 3 / 3
|
3
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] ."
reach
"Subsequent experiments further suggested that OTUB1 promoted CRC malignancy by enhancing protein stability of β-catenin, via inhibition of its protein degradation by UPP pathway, which indicated its crucial role in enhancement of CRC tumor cellular proliferative and chemo-resistant capabilities."
reach
"At the same time, a high level of N-cadherin expression blocks beta-catenin entry into the nucleus [XREF_BIBR], so the changes in beta-catenin mediated by OTUB1 were observed in the cytoplasm in our model, which might be the reason why TCF1, LEF1 were not activated in our models (Additional file 11 : Figure S9)."
K48-Ub 2 affects OTUB1
|
3
FOXM1 over-expression affects OTUB1
|
3
DOA1 affects Cdc48
|
3
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
Polyubiquitin affects Ubiquitin
|
2
Hsa-miR-542-3p affects OTUB1
2
|
Endoplasmic reticulum affects OTUB1
|
2
Bisphenol A affects OTUB1
2
|
sparser
"Superimpositions of TYMV PRO/DUB with cellular OTU DUBs show that yeast OTU1 and human OTUD2 also interact simultaneously with the two hydrophobic patches of Ub (Fig. S3A) but engage mainly hydrophobic residues, together with one charged residue that structurally resembles Arg844 of TYMV PRO/DUB, i.e. Glu203 in yOTU1 or Arg245 in hOTUD2 (Fig. S3)."
sparser
"Superimpositions of TYMV PRO/DUB with cellular OTU DUBs show that yeast OTU1 and human OTUD2 also interact simultaneously with the two hydrophobic patches of Ub () but engage mainly hydrophobic residues, together with one charged residue that structurally resembles Arg 844 of TYMV PRO/DUB, i.e. Glu 203 in yOTU1 or Arg 245 in hOTUD2 ()."
Ubiquitin affects polyubiquitin
|
2
Ubiquitin affects OtDUB
|
2
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
SMAD3 affects Hemagglutinins
|
2
OTUB1 binds SMAD3, Hemagglutinins, and FlaG. 2 / 2
|
2
SMAD2/3/4 affects OTUB1
|
1
RA-9 affects OTUB1
|
2
OtDUB affects Ubiquitin
|
2
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
|
2
OTUB1 affects ubiquitination degradation FOXM1 breast cancer
|
2
OTUB1 affects ubiquitin transfer
|
2
OTUB1 affects transcriptional HSF1
|
2
OTUB1 affects transcription, DNA-templated
|
2
OTUB1 affects protein stability HSF1
|
2
OTUB1 affects polyubiquitin
|
2
OTUB1 affects phenazine-1-carboxylate
|
2
OTUB1 affects p53S46P
|
2
OTUB1 affects p53-S46P
|
2
OTUB1 affects p53 ubiquitination
|
2
eidos
"For example , USP7 regulates the stability of both p53 and Mdm2 and maintains p53 ubiquitination levels ; 120 USP2 mediates the stability of Mdm2 ; 121 USP10 modulates p53 localization and stability ; 122 OTUB1 abrogates p53 ubiquitination and activates p53.123 Interestingly , USP10 can stabilize both mutated and wild-type p53 , with a dual role in tumorigenesis ."
eidos
"For example , USP7 modulates the stability of both p53 and MDM2 , and maintains the level of p53 ubiquitylation ( 34 , 87 ) ; USP2 affects the stability of MDM2 ( 88 ) ; Otub1 inhibits p53 ubiquitination and activates p53 in cells ( 56 ) ; USP10 regulates the location and stability of p53 , and stabilize both mutated and wild-type p53 , thereby having a dual role in tumorigenesis ( 89 ) ."
OTUB1 affects oestrogen receptor alpha TRAF3 small
|
2
OTUB1 affects migration
|
2
OTUB1 affects miR-542-3p
|
2
OTUB1 affects localization
|
2
OTUB1 affects lethal hepatocyte necroptosis
|
2
OTUB1 affects inflammatory response
|
2
OTUB1 affects function
|
2
OTUB1 affects formation
|
2
OTUB1 affects epithelial-mesenchymal transition endometriosis cells
|
2
OTUB1 affects endoplasmic reticulum
|
2
OTUB1 affects chain
|
2
OTUB1 affects cell migration
|
2
OTUB1 affects c-Maf polyubiquitination
|
2
OTUB1 affects autoubiquitination UBE2E1
|
2
OTUB1 affects activity
|
2
OTUB1 affects activation
|
2
sparser
"Superimpositions of TYMV PRO/DUB with cellular OTU DUBs show that yeast OTU1 and human OTUD2 also interact simultaneously with the two hydrophobic patches of Ub (Fig. S3A) but engage mainly hydrophobic residues, together with one charged residue that structurally resembles Arg844 of TYMV PRO/DUB, i.e. Glu203 in yOTU1 or Arg245 in hOTUD2 (Fig. S3)."
sparser
"Superimpositions of TYMV PRO/DUB with cellular OTU DUBs show that yeast OTU1 and human OTUD2 also interact simultaneously with the two hydrophobic patches of Ub () but engage mainly hydrophobic residues, together with one charged residue that structurally resembles Arg 844 of TYMV PRO/DUB, i.e. Glu 203 in yOTU1 or Arg 245 in hOTUD2 ()."
sparser
"We unexpectedly find that OTUB1 binding to UBC13∼Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13∼Ub, while at the same time disrupting interactions with UEV1A in a manner that depends on the OTUB1 N terminus."
sparser
"We unexpectedly find that OTUB1 binding to UBC13~Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13~Ub, while at the same time disrupting interactions with UEV1a in a manner that depends upon the OTUB1 N-terminus."
OTUB1 affects SMAD2/3/4
|
1
OTUB1 affects RT4 cells
|
2
OTUB1 affects R-SMAD SMAD4 complex
|
2
OTUB1 affects Protein Stability
|
2
OTUB1 activates Protein Stability. 2 / 2
|
2
OTUB1 affects PD-L1 abundance
|
2
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains.[
172
] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
OTUB1 affects Infections
|
2
reach
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
sparser
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
reach
"In lethally irradiated mice reconstituted with bone marrow cells from T cell receptor-transgenic mice retrovirally transduced to express the genes encoding these proteases, otubain 1 expressing cells contained negligible amounts of endogenous GRAIL, proliferated well and produced large amounts of interleukin 2 after antigenic stimulation."
OTUB1 affects IH
|
2
OTUB1 affects Hemagglutinins
|
2
OTUB1 binds SMAD3, Hemagglutinins, and FlaG. 2 / 2
|
2
sparser
"In the in vitro ubiquitination assay, individual Flag-tagged substrates (MSH2, FOXM1, and DEPTOR) were incubated with GST-OTUB1 (WT, C91A, or D88A) and HA-Ub in a ubiquitination system containing rabbit reticulocyte lysate (RRL), as described previously ( xref ), and ubiquitinated substrates were visualized by western blotting using a Ub antibody."
OTUB1 affects EN523
|
2
OTUB1 affects E3_Ub_ligase
|
1
1
OTUB1 inhibits E3_Ub_ligase. 2 / 2
|
1
1
OTUB1 affects E2~Ub
|
2
OTUB1 affects E2F1 protein
|
2
OTUB1 affects Dendritic Cells
|
2
OTUB1 affects DNA Damage
|
1
OTUB1 inhibits DNA Damage. 1 / 2
|
1
reach
"These data suggest that OTU1 negatively regulates expression of DA1 and DA2 and that its loss of function results in transcriptional activation of these target genes.DA1, a ubiquitin-binding protein, and DA2, a RING-type E3 ubiquitin ligase, are known to interact with each other and negatively regulate the seed and organ size in Arabidopsis (Du et al., 2014, Li and Li, 2014, Li and Li, 2016, Xia et al., 2013)."
sparser
"We cannot rule out that at least some of the cytoplasmic signal of CFP-OTU1 derives from degradation of this fusion protein; however, usually, degradation of GFP-tagged proteins results in the loss of fluorescence, representing the rationale for degradation assays that utilize GFP fusions of the proteins of interest ( xref , xref , xref )."
sparser
"As positive control for nuclear localization, CFP-OTU1 was coexpressed with mRFP fused to a bipartite-type nuclear localization signal (NLS) derived from the Agrobacterium VirD2 protein ( xref ). xref B shows that, similarly to free mRFP, CFP-OTU1 accumulated in the cytoplasm—displaying transvacuolar strands (green arrowhead) and variations in cytosol thickness at the cell cortex ( xref , xref )—and in the nucleus (white arrowhead), colocalizing with mRFP-VirD2 NLS."
Nam affects OTUB1
|
2
reach
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
sparser
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
Hemagglutinins affects SMAD3
|
2
OTUB1 binds SMAD3, Hemagglutinins, and FlaG. 2 / 2
|
2
sparser
"In the in vitro ubiquitination assay, individual Flag-tagged substrates (MSH2, FOXM1, and DEPTOR) were incubated with GST-OTUB1 (WT, C91A, or D88A) and HA-Ub in a ubiquitination system containing rabbit reticulocyte lysate (RRL), as described previously ( xref ), and ubiquitinated substrates were visualized by western blotting using a Ub antibody."
OTUB1 binds SMAD3, Hemagglutinins, and FlaG. 2 / 2
|
2
E4B affects OTUB1
|
2
E2~Ub affects OTUB1
|
2
sparser
"We cannot rule out that at least some of the cytoplasmic signal of CFP-OTU1 derives from degradation of this fusion protein; however, usually, degradation of GFP-tagged proteins results in the loss of fluorescence, representing the rationale for degradation assays that utilize GFP fusions of the proteins of interest ( xref , xref , xref )."
sparser
"As positive control for nuclear localization, CFP-OTU1 was coexpressed with mRFP fused to a bipartite-type nuclear localization signal (NLS) derived from the Agrobacterium VirD2 protein ( xref ). xref B shows that, similarly to free mRFP, CFP-OTU1 accumulated in the cytoplasm—displaying transvacuolar strands (green arrowhead) and variations in cytosol thickness at the cell cortex ( xref , xref )—and in the nucleus (white arrowhead), colocalizing with mRFP-VirD2 NLS."
AM146 affects OTUB1
|
2
ACTN1 affects ANXA3, CANX, CNN2, CTNNB1, CTPS1, EPRS1, GLO1, GPI, HMGB1, ITGB1, MAPK1, MAPK3, MYH9, MYO1E, OTUB1, PRDX3, PSMA2, PSMB6, PSME2, RPL22, RPS19, RPS24, SAMHD1, SEC61A1, SYNCRIP, TCAF2, and TPM1
|
2
RPL22 binds RPS19, RPS24, TPM1, CANX, SAMHD1, ACTN1, SYNCRIP, SEC61A1, CNN2, OTUB1, CTNNB1, CTPS1, TCAF2, EPRS1, GLO1, GPI, HMGB1, ANXA3, ITGB1, MAPK1, MAPK3, MYH9, MYO1E, PRDX3, PSMA2, PSMB6, and PSME2. 2 / 2
|
2
sparser
"MYH9, ACTN1, CANX, GPI, TPM1, EPRS, ITGB1, ANXA3, CNN2, MAPK1, PSME2, CTPS1, OTUB1, PSMB6, HMGB1, RPS19, SEC61A1, CTNNB1, GLO1, RPL22, PSMA2, SYNCRIP, PRDX3, SAMHD1, TCAF2, MAPK3, RPS24, and MYO1E, which are associated with immunity, were expressed at higher levels by the SCID mAdMSCs compared with the C57BL/6 mAdMSCs."
sparser
"However, MYH9, ACTN1, CANX, GPI, TPM1, EPRS, ITGB1, ANXA3, CNN2, MAPK1, PSME2, CTPS1, OTUB1, PSMB6, HMGB1, RPS19, SEC61A1, CTNNB1, GLO1, RPL22, PSMA2, SYNCRIP, PRDX3, SAMHD1, TCAF2, MAPK3, RPS24, and MYO1E, which are associated with immunity, were more highly expressed by SCID mAdMSCs compared with those of C57BL/6 mAdMSCs."
Targeting C57BL affects OTUB1
|
1
Sodium citrate dihydrate affects OTUB1
|
1
Sodium citrate dihydrate activates OTUB1. 1 / 1
|
1
P53-S46P affects OTUB1
|
1
Hydroperoxide affects OTUB1
1
|
Hsa-miR-708-3p affects OTUB1
1
|
Hsa-miR-6752-5p affects OTUB1
1
|
Hsa-miR-6732-5p affects OTUB1
1
|
Hsa-miR-6722-3p affects OTUB1
1
|
Hsa-miR-663a affects OTUB1
1
|
Hsa-miR-4706 affects OTUB1
1
|
Hsa-miR-4504 affects OTUB1
1
|
Hsa-miR-3185 affects OTUB1
1
|
Hsa-miR-3180-3p affects OTUB1
1
|
Hsa-miR-3179 affects OTUB1
1
|
Hsa-miR-3154 affects OTUB1
1
|
Hsa-miR-28-5p affects OTUB1
1
|
Hsa-miR-15a-5p affects OTUB1
1
|
Hsa-miR-143-5p affects OTUB1
1
|
Cyclosporin A affects OTUB1
|
1
Cyclosporin A activates OTUB1. 1 / 1
|
1
Cobalt dichloride affects OTUB1
1
|
Ubvs affects OTUB1
|
1
UbVS affects OTUB1
|
1
Ub moiety affects OTUB1
|
1
UBE2E enzymes affects OTUB1
|
1
reach
"47
Treating ccRCC cells with MG132 to inhibit SIRT3 ubiquitination, we found that knocking down NUDT1 can significantly reduce the expression of OTUB1 that binds to SIRT3, which indicates that OTUB1 plays an important role in the process of NUDT1 affecting SIRT3 ubiquitination (Figure 4H)."
| PMC
PolyUb chains affects OTUB1
|
1
OTUB1 affects xenograft tumor growth
|
1
OTUB1 affects wound healing
|
1
OTUB1 activates wound healing. 1 / 1
|
1
OTUB1 affects vivo.4 DISCUSSION
|
1
OTUB1 affects ubiquitination ovarian cancer breast cancer
|
1
OTUB1 affects ubiquitination of FOXM1 in RCC
|
1
OTUB1 affects ubiquitination E2F1 induced overexpression TMPO-AS1 cells
|
1
OTUB1 affects ubiquitin response RNF8 RNF168
|
1
OTUB1 affects tumor migration
|
1
OTUB1 affects subsequent
|
1
OTUB1 affects stability cIAP1
|
1
OTUB1 affects signaling
|
1
OTUB1 affects production
|
1
OTUB1 affects process
|
1
OTUB1 affects mutator MMR proteins MutSalpha play damage signaling
|
1
OTUB1 affects metastasis esophageal squamous cell carcinoma
|
1
eidos
"Based on these findings of previous studies , OTUB1 promotes the metastasis of esophageal squamous cell carcinoma by modulating snail stability ( Zhou et al ., 2018 ) , while different expression of OTUB1 affects the migration and progression of colorectal cancer through the regulation of ERRalpha or mir-542-3p ( Yuan et al ., 2017 ; Zhou et al ., 2019 ) ."
OTUB1 affects isopeptidase
|
1
OTUB1 affects invasion cells
|
1
OTUB1 affects hypoxia-induced glycolytic reprogramming cellular metabolic adaptation
|
1
OTUB1 affects drug sensitivity
|
1
OTUB1 affects deubiquitination stabilization replication A protein RPA1
|
1
eidos
"Nuclear PTEN also maintains genome stability through multiple mechanisms such as inducing DNA repair protein RAD51 to positively regulate DNA repair through its interaction with centromere protein C17 ,18 , and recruiting the deubiquitinase OTU domain-containing ubiquitin aldehyde-binding protein 1 ( OTUB1 ) to mediate deubiquitination and stabilization of replication factor A protein 1 ( RPA1 ) 19 ."
OTUB1 affects deubiquitination TRAF3
|
1
OTUB1 affects deubiquitination TRAF3 TRAF6
|
1
OTUB1 affects deubiquitination FOXM1 breast cancer ovarian cancer
|
1
OTUB1 affects cell viability file Figure S1B
|
1
OTUB1 affects biosynthetic process
|
1
OTUB1 bound to UBE2N inhibits biosynthetic process. 1 / 1
|
1
OTUB1 affects autoubiquitination
|
1
OTUB1 affects UbVS
|
1
OTUB1 affects Ub moiety
|
1
OTUB1 affects USP10 stabilize mutated wild-type p53 dual tumorigenesis
|
1
eidos
"For example , USP7 regulates the stability of both p53 and Mdm2 and maintains p53 ubiquitination levels ; 120 USP2 mediates the stability of Mdm2 ; 121 USP10 modulates p53 localization and stability ; 122 OTUB1 abrogates p53 ubiquitination and activates p53.123 Interestingly , USP10 can stabilize both mutated and wild-type p53 , with a dual role in tumorigenesis ."
OTUB1 affects UBE2E families
|
1
OTUB1 affects UBE2E enzymes
|
1
OTUB1 affects UBE2D/2E family
|
1
OTUB1 affects UBE2D
|
1
reach
"47
Treating ccRCC cells with MG132 to inhibit SIRT3 ubiquitination, we found that knocking down NUDT1 can significantly reduce the expression of OTUB1 that binds to SIRT3, which indicates that OTUB1 plays an important role in the process of NUDT1 affecting SIRT3 ubiquitination (Figure 4H)."
| PMC
OTUB1 affects RNF8-Ubc13
|
1
OTUB1 affects RIG-I-, MDA5-,
|
1
OTUB1 affects Proteasome
|
1
OTUB1 leads to the ubiquitination of Proteasome. 1 / 1
|
1
reach
"Given that OTUB1 has been shown to restrict the ubiquitination and proteasome degradation of target proteins in response to DNA damage, 17 we asked whether FOXM1 is also downregulated through protein degradation by the ubiquitin-proteasome pathway and tested the effect of the proteasome inhibitor MG132 treatment on the expression of endogenous FOXM1 in the absence or presence of epirubicin in MCF-7 cells (XREF_FIG)."
OTUB1 affects Polyubiquitin
|
1
OTUB1 bound to UBE2N inhibits Polyubiquitin 1 / 1
|
1
OTUB1 affects PolyUb chains
|
1
OTUB1 affects PC3 C4-2 cells
|
1
OTUB1 affects MutSalpha
|
1
OTUB1 affects MAG
|
1
sparser
"Besides taxon-specific clustering patterns that were evident from 16S rRNA gene profiles and sequence content of the MAGs, OTU1-dominated symbiont-specific transcriptomes formed two separate subclusters based on whether specimens were collected from alga-covered and seagrass-covered quadrats ( xref and xref ), although these transcriptomes shared 0.9 ± 0.01 average pairwise PCC with each other."
OTUB1 affects Lys48
|
1
OTUB1 affects K63-Ub
|
1
OTUB1 affects Invasion PCa Cell
|
1
OTUB1 affects IKK_complex
|
1
OTUB1 inhibits IKK_complex. 1 / 1
|
1
OTUB1 affects IFN-I
|
1
OTUB1 affects Growth PC3
|
1
OTUB1 affects FOXM1 transcription
|
1
reach
"Wild-type OTUB1 and the DeltaN mutant, both capable of cleaving K48 linked di- or polyubiquitin chains in vitro, along with all the catalytically inactive mutants (D88A, C91S, H265A, D/H, D/C/H, K71R) were not able to deubiquitylate the polyubiquitylated FLAG and SMAD2/3/4 complex (XREF_FIG)."
OTUB1 affects Carcinoma, Renal Cell
|
1
OTUB1 activates Carcinoma, Renal Cell. 1 / 1
|
1
OTUB1 affects CFPAC-1 cells
|
1
NS1 proteins affects OTUB1
|
1
MAG affects OTUB1
|
1
sparser
"Besides taxon-specific clustering patterns that were evident from 16S rRNA gene profiles and sequence content of the MAGs, OTU1-dominated symbiont-specific transcriptomes formed two separate subclusters based on whether specimens were collected from alga-covered and seagrass-covered quadrats ( xref and xref ), although these transcriptomes shared 0.9 ± 0.01 average pairwise PCC with each other."
Lys48 affects OTUB1
|
1
HA-UbBr2 affects OTUB1
|
1
CTLA-4 receptors affects OTUB1
|
1
17beta-estradiol affects OTUB1
|
1
17beta-estradiol binds OTUB1. 1 / 1
|
1
2,3',4,4',5-pentachlorobiphenyl affects OTUB1
1
|