OTUD1 Data Analysis

HGNC Gene Name
OTU deubiquitinase 1
HGNC Gene Symbol
OTUD1
Identifiers
hgnc:27346 NCBIGene:220213 uniprot:Q5VV17
Orthologs
mgi:1918448 rgd:1563344
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for OTUD1
Number of Papers
30 retrieved on 2022-05-22

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with OTUD1using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value

Literature Mining

INDRA was used to automatically assemble known mechanisms related to OTUD1 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

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OTUD1 deubiquitinates SMAD7. 5 / 5
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Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7

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This confirms that OTUD1 deubiquitinates SMAD7 in vitro.

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OTUD1 deubiquitinates SMAD7 and sustains SMAD7 stability.

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Further investigation reveals that OTUD1 directly deubiquitinates the TGF-beta pathway inhibitor SMAD7 and prevents its degradation.

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To demonstrate that OTUD1 can directly deubiquitinate SMAD7, we performed in vitro deubiquitination assays.
OTUD1 deubiquitinates TP53. 4 / 4
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OTUD1, OTUD5 and USP11 directly deubiquitinating p53 and functional proteins were required for p53 stabilization [XREF_BIBR - XREF_BIBR].

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Review

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Our results showed that OTUD1 deubiquitinated p53 and that functional OTUD1 was required for p53 stabilization.

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Our results showed that OTUD1 deubiquitinated p53 and that functional OTUD1 was required for p53 stabilization.
OTUD1 leads to the deubiquitination of ART4. 1 / 1
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The level of Art4-OTUD1 fusion in ubp2Delta ubp15Delta cells, however, was nearly identical to that in WT cells (XREF_FIG, lanes 5 and 6, and C), suggesting that OTUD1 efficiently prevents Art4 hype-r-ubiquitination.
OTUD1 leads to the deubiquitination of MAVS. 1 / 1
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Furthermore, OTUD1 induced upregulation of the E3 ubiquitin ligase Smurf1 by deubiquitinating Smurf1, and Smurf1 degraded MAVS in MDBK cells in a ubiquitination dependent manner, ultimately inhibiting IFN-I production.
OTUD1 deubiquitinates TGFB. 1 / 1
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Further investigation reveals that OTUD1 directly deubiquitinates the TGF-beta pathway inhibitor SMAD7 and prevents its degradation.
OTUD1 leads to the deubiquitination of SMURF1. 1 / 1
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Furthermore, OTUD1 induced upregulation of the E3 ubiquitin ligase Smurf1 by deubiquitinating Smurf1, and Smurf1 degraded MAVS in MDBK cells in a ubiquitination dependent manner, ultimately inhibiting IFN-I production.
OTUD1 deubiquitinates CARD9. 1 / 1
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OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9.

Other Statements

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OTUD1 affects SMURF1
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OTUD1 increases the amount of SMURF1.
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OTUD1 increases the amount of SMURF1. 4 / 4
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For example, OTUD1 upregulates the protein levels of intracellular Smurf1 by removing the K48-linked polyubiquitin chains of Smurf1, and RNA virus infection promotes the binding of Smurf1 to MAVS, TRAF3, and TRAF6, which leads to ubiquitination-dependent degradation of the three proteins and subsequent potent inhibition of IFNs production (64).

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Furthermore, OTUD1 upregulates protein levels of intracellular Smurf1 by removing Smurf1 ubiquitination.

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And OTUD1 upregulates Smurf1 protein levels by removing ubiquitination of Smurf1.

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Thus, these data demonstrate that OTUD1 positively regulates cellular levels of Smurf1 by deubiquitination effects.
Modified OTUD1 increases the amount of SMURF1. 4 / 4
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RNA virus infection promotes NF-kappaB-dependent expression of OTUD1 that upregulates Smurf1 protein levels.

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We further found that OTUD1 overexpression upregulated protein level of Smurf1, rather than Smurf2 (XREF_SUPPLEMENTARY).

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Overexpression of OTUD1 upregulated exogenous Smurf1 protein levels in a dose dependent manner (XREF_FIG).

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In this study, we reveal that RNA virus infection activates expression of OTUD1, which in turn interacts with Smurf1 and upregulates Smurf1 protein levels by deubiquitination effects.
OTUD1 activates SMURF1.
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OTUD1 activates SMURF1. 2 / 2
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Next, we analyzed the deubiquitination types of Smurf1 mediated by OTUD1 using two ubiquitin mutants, Ub-R48K (all lysines in Ub are mutated to arginines except lysine 48 residue) and Ub-R63K (all lysines in Ub are mutated to arginines except lysine 63 residue).

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RNA virus induced OTUD1 protein regulates Smurf1 ubiquitination and increases the level of Smurf1 protein.
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Importantly, OTUD1 is lost in multiple types of human cancers and loss of OTUD1 increases metastasis in intracardial xenograft and orthotopic transplantation models, and correlates with poor prognosis among breast cancer patients.

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Moreover, ectopic expression of OTUD1 significantly inhibited metastasis in control cells but did not show significant inhibitory effect in the SMAD7 knockout cells.

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Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7.

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Therefore, our studies suggest that OTUD1 inhibits lung metastasis in transplantable mouse models.

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OTUD1 inhibits metastasis in transplantable mouse models.

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Although cell transplantation induced bone metastasis to similar levels around day 21 post-injection, expression of OTUD1 wild-type (wt) beginning at day 21 significantly suppressed metastasis around day 35, which also led to increased mice survival.

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Thus, OTUD1 represses breast cancer metastasis by mitigating TGF-beta-induced pro oncogenic responses via deubiquitination ofSMAD7.

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Taken together, these analyses show that loss of OTUD1 strongly promotes breast cancer lung metastasis.
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OTUD1 is a deubiquitinase and among its targets is SMAD7, and OTUD1 deficiency destabilizes SMAD7 and potentiates TGF-beta1-driven metastasis [XREF_BIBR].
OTUD1 affects MAVS
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OTUD1 decreases the amount of MAVS.
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OTUD1 decreases the amount of MAVS. 3 / 3
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OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6.

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Together, these data suggest that OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6.

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In this study, we uncovered that OTUD1 can downregulate protein levels of MAVS, TRAF3 and TRAF6.
Modified OTUD1 decreases the amount of MAVS. 1 / 1
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However, we noticed that OTUD1 overexpression gradually downregulated the levels of MAVS, TRAF3, and TRAF6 (XREF_FIG), which is consistent with the observation that OTUD1 overexpression inhibits the induction of type I IFNs and proinflammatory cytokines.
OTUD1 inhibits MAVS.
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OTUD1 inhibits MAVS. 2 / 2
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These data indicate that OTUD1 inhibits the IFNs antiviral response downstream of MAVS and upstream of TBK1.

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In the presence of MG132, the ability of OTUD1 to downregulate MAVS (XREF_FIG), or TRAF3 (XREF_FIG), or TRAF6 (XREF_FIG) was largely inhibited.
OTUD1 activates MAVS.
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OTUD1 activates MAVS. 2 / 2
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Therefore, we tried to analyze whether Smurf1 could be required for OTUD1 mediated downregulation of MAVS.

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Our data showed that knockdown of Smurf1 significantly inhibited OTUD1 mediated MAVS downregulation (XREF_FIG).
OTUD1 affects TRAF6
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OTUD1 decreases the amount of TRAF6.
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OTUD1 decreases the amount of TRAF6. 3 / 3
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Together, these data suggest that OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6.

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OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6.

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In this study, we uncovered that OTUD1 can downregulate protein levels of MAVS, TRAF3 and TRAF6.
Modified OTUD1 decreases the amount of TRAF6. 1 / 1
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Similarly, OTUD1 overexpression lowered protein levels of TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG).
OTUD1 inhibits TRAF6.
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OTUD1 inhibits TRAF6. 2 / 2
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Interestingly, Smurf1 knockdown also remarkably blocked OTUD1 mediated downregulation of both TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG).

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In the presence of MG132, the ability of OTUD1 to downregulate MAVS (XREF_FIG), or TRAF3 (XREF_FIG), or TRAF6 (XREF_FIG) was largely inhibited.
Modified OTUD1 inhibits TRAF6. 1 / 1
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However, we noticed that OTUD1 overexpression gradually downregulated the levels of MAVS, TRAF3, and TRAF6 (XREF_FIG), which is consistent with the observation that OTUD1 overexpression inhibits the induction of type I IFNs and proinflammatory cytokines.
OTUD1 affects TRAF3
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OTUD1 decreases the amount of TRAF3.
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OTUD1 decreases the amount of TRAF3. 3 / 3
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In this study, we uncovered that OTUD1 can downregulate protein levels of MAVS, TRAF3 and TRAF6.

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Together, these data suggest that OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6.

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OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6.
Modified OTUD1 decreases the amount of TRAF3. 1 / 1
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Similarly, OTUD1 overexpression lowered protein levels of TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG).
OTUD1 inhibits TRAF3.
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OTUD1 inhibits TRAF3. 2 / 2
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In the presence of MG132, the ability of OTUD1 to downregulate MAVS (XREF_FIG), or TRAF3 (XREF_FIG), or TRAF6 (XREF_FIG) was largely inhibited.

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Interestingly, Smurf1 knockdown also remarkably blocked OTUD1 mediated downregulation of both TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG).
Modified OTUD1 inhibits TRAF3. 1 / 1
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However, we noticed that OTUD1 overexpression gradually downregulated the levels of MAVS, TRAF3, and TRAF6 (XREF_FIG), which is consistent with the observation that OTUD1 overexpression inhibits the induction of type I IFNs and proinflammatory cytokines.
OTUD1 affects Interferon
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OTUD1 inhibits Interferon.
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Hence , OTUD1 cleaves the K6-linked ubiquitin chain and leads to the disassociation of IRF3 from the promoter region of target genes , thereby attenuating type I IFN induction .

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Taken together, these results suggest that both Smurf1 and the deubiquitinase activity of OTUD1 are required for the downregulation of MAVS/TRAF3/TRAF6 signalosome proteins, which results in the OTUD1 mediated inhibition of interferon antiviral response.

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The aforementioned results prove that Smurf1 is important for OTUD1 mediated inhibition of interferon antiviral response.

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OTUD1 Negatively Regulates Type I IFN Induction by Disrupting Noncanonical Ubiquitination of IRF3.

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] OTUD1 was also reported to inhibit IFN production during RNA virus infection .
OTUD1 activates Interferon.
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Both Smurf1 and the deubiquitinase activity of OTUD1 are required for OTUD1 mediated downregulation of MAVS/TRAF3/TRAF6 and inhibition of interferon antiviral response.
OTUD1 affects EAF2
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OTUD1 inhibits EAF2. 5 / 5
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These results suggest that OTUD1 reduces the manifestation of cancer stem cell traits.

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Combined, the in vitro and in vivo evidence in this study elucidates critical functions of OTUD1 in the termination of TGF-beta and SMAD-induced metastatic activation, indicating that OTUD1 restricts the EMT and cancer stem cell traits during metastasis.

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OTUD1 inhibits cancer stem cell traits.

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OTUD1 inhibits cancer stem cell traits.

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From our screen, we have identified that loss of OTUD1 enables breast cancer cells to undergo EMT and gain cancer stem cell traits thereby driving metastatic spread to distant organs, such as bone and lung.
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Melatonin induces apoptotic cell death through Bim stabilization by Sp1-mediated OTUD1 upregulation.

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Next, we confirmed that OTUD1 overexpression increased the cleavage of caspase-3 and PARP and subsequently increased apoptosis.

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OTUD1 knockdown inhibited melatonin-induced Bim upregulation and apoptosis in cancer cells .
OTUD1 affects SMAD7
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OTUD1 activates SMAD7. 4 / 4
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By doing so, OTUD1 enables SMAD7 function thereby antagonizing TGF-beta and SMAD signaling.

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Ectopic expression of OTUD1-wt, but not OTUD1-CA, prolonged the half-life of endogenous SMAD7.

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The deubiquitinase OTUD1 was found to enable the antagonistic role of SMAD7 on TGF-beta signaling.

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Given our results that OTUD1 enables SMAD7 and SMURF2 function, we examined whether OTUD1 misexpression can regulate TbetaRI levels at the cell surface, the location where intracellular signaling is initiated.
OTUD1 affects IFNB1
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OTUD1 inhibits IFNB1.
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OTUD1 inhibits IFNB1. 3 / 3
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The result showed that knockdown of OTUD1 promoted SeV induced IFNbeta production (XREF_FIG and XREF_SUPPLEMENTARY).

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Our data showed that overexpression of OTUD1 inhibited the production of IFNbeta in response to SeV infection, whereas knockdown of Smurf1 largely blocked the negative regulation of OTUD1 on IFNbeta production (XREF_FIG), indicating that Smurf1 is required for OTUD1 mediated inhibition of interferon antiviral response.

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During infection with SeV, overexpression of OTUD1-wild type obviously lowered the activity of IFNbeta promoter, whereas overexpression of OTUD1-CH mutant completely had no effect on the IFNbeta promoter activity (XREF_FIG), suggesting that the deubiquitinase activity of OTUD1 is important for OTUD1 mediated inhibition of IFNbeta production during viral infection.
OTUD1 activates IFNB1.
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OTUD1 activates IFNB1. 1 / 1
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At day 3 after VSV infection, Otud1 -/- mice produced much higher expression of IFNbeta and IL-6 mRNAs (XREF_FIG), and had much lower viral RNAs (XREF_FIG) in their lung tissue than did Otud1 +/+ mice.

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From our screen, we have identified that loss of OTUD1 enables breast cancer cells to undergo EMT and gain cancer stem cell traits thereby driving metastatic spread to distant organs, such as bone and lung.

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OTUD1 causes suppression of TGF-beta downstream signals and EMT.

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Combined, the in vitro and in vivo evidence in this study elucidates critical functions of OTUD1 in the termination of TGF-beta and SMAD-induced metastatic activation, indicating that OTUD1 restricts the EMT and cancer stem cell traits during metastasis.
OTUD1 affects TGFB
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OTUD1 inhibits TGFB. 3 / 3
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We next investigated the molecular mechanism by which OTUD1 inhibits TGF-beta and SMAD signaling.

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Ectopic expression of OTUD1 could suppress TGF-beta signaling in control cells but barely showed effect in SMAD7 deficient cells; also knockdown of OTUD1 could promote TGF-beta signaling in control cells but not in SMAD7 deficient cells, suggesting thatinhibitory SMAD7 might be the major target of OTUD1 in the TGF-beta pathway.

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OTUD1 causes suppression of TGF-beta downstream signals and EMT.
OTUD1 affects SMURF2
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OTUD1 activates SMURF2.
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OTUD1 activates SMURF2. 2 / 2
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Given our results that OTUD1 enables SMAD7 and SMURF2 function, we examined whether OTUD1 misexpression can regulate TbetaRI levels at the cell surface, the location where intracellular signaling is initiated.

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In line with this, knockdown of OTUD1, which results in increased K33-poly-ubiquitin conjugation on SMAD7 K220, reduced the ability of SMURF2 to interact with SMAD7.
OTUD1 increases the amount of SMURF2.
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Modified OTUD1 increases the amount of SMURF2. 1 / 1
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We further found that OTUD1 overexpression upregulated protein level of Smurf1, rather than Smurf2 (XREF_SUPPLEMENTARY).
Tetrachloromethane increases the amount of OTUD1. 2 / 2
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Phenylmercury acetate decreases the amount of OTUD1. 2 / 2
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Paracetamol affects OTUD1
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Paracetamol increases the amount of OTUD1. 2 / 2
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Melatonin affects OTUD1
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Furthermore, melatonin reduced tumor growth and induced upregulation of OTUD1 and Bim in a mouse xenograft model.

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Melatonin-induced OTUD1 upregulation caused deubiquitnation at the lysine 3 residue of Bim, resulting in its stabilization.
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Hsa-miR-19b-3p decreases the amount of OTUD1. 2 / 2
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Hsa-miR-181a-5p decreases the amount of OTUD1. 2 / 2
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Cyclosporin A increases the amount of OTUD1. 2 / 2
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No evidence text available

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No evidence text available
SP1 affects OTUD1
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SP1 activates OTUD1. 2 / 2
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Melatonin induces apoptotic cell death through Bim stabilization by Sp1-mediated OTUD1 upregulation.

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Thus, our results demonstrated that melatonin induced apoptosis by stabilizing Bim via Sp1-mediated OTUD1 upregulation.
OTUD1 affects TP53
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OTUD1 activates TP53. 1 / 2
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OTUD1 overexpression increased p53 stability, whereas OTUD1 knockdown decreased p53 stability.
OTUD1 affects RLR
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OTUD1 inhibits RLR. 2 / 2
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Our study clearly demonstrates that the deubiquitinase OTUD1 negatively regulates RLR signaling.

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Finally, the deubiquitinase OTUD1 potently inhibits RLR pathway by utilizing Smurf1-MAVS/TRAF3/TRAF6 signaling at the early stage of viral infection.
OTUD1 affects MDM2
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OTUD1 increases the amount of MDM2. 1 / 2
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We also found that wild-type OTUD1 upregulated p21 and Mdm2 expression but inactive OTUD1 mutant did not.
OTUD1 affects BCL2L11
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OTUD1 activates BCL2L11. 2 / 2
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In addition, melatonin-induced activation of Sp1 was found to be involved in OTUD1 upregulation at the transcriptional level, and pharmacological inhibition and genetic ablation of Sp1 (siRNA) interrupted melatonin-induced OTUD1-mediated Bim upregulation.

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Melatonin induces apoptotic cell death through Bim stabilization by Sp1-mediated OTUD1 upregulation.
HRAS affects OTUD1
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HRAS decreases the amount of OTUD1. 2 / 2
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Similar as the BRCA1 and BRCA2 tumor suppressors, expression of OTUD1 was significantly suppressed by wild-type HRAS in p53 null MCF10A cells, but not in the control MCF10A cells (p53-wt), indicating that gain of oncogenic RAS together with loss of p53 tumor suppressor could lead to decreased OTUD1 function (GSE81593).

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Consistent with the notion that activation of HRAS inhibits OTUD1 expression in p53 mutant cells, we found that upon ectopic expression of constitutively active HRASV12, OTUD1 is downregulated in p53 mutant MDA-MB-231 (both the early passage and the bone-metastatic (BM) cell lines) but not in p53 wt MCF7 cells, TGF-beta and HRAS collaborate to promote EMT, invasion and cancer stem traits in breast cancer cells 36.
DDIT3 affects OTUD1
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DDIT3 increases the amount of OTUD1. 2 / 2
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Importantly, DDIT3 induced OTU deubiquitinase 1 (OTUD1) expression by activating the NF-kappaB signaling pathway, thus increasing intracellular Smurf1 protein levels to degrade MAVS and inhibit IFN-I production during BVDV infection.

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DDIT3 promoted NF-kappaB-dependent OTU deubiquitinase 1 (OTUD1) expression.
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Bisphenol A affects OTUD1
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Bisphenol A increases the amount of OTUD1.
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Bisphenol A increases the amount of OTUD1. 1 / 1
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Bisphenol A decreases the amount of OTUD1.
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Bisphenol A decreases the amount of OTUD1. 1 / 1
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Benzo[a]pyrene increases the amount of OTUD1.
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Benzo[a]pyrene increases the amount of OTUD1. 1 / 1
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Benzo[a]pyrene decreases the amount of OTUD1.
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Benzo[a]pyrene decreases the amount of OTUD1. 1 / 1
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All-trans-retinoic acid increases the amount of OTUD1.
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All-trans-retinoic acid increases the amount of OTUD1. 1 / 1
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All-trans-retinoic acid decreases the amount of OTUD1.
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All-trans-retinoic acid decreases the amount of OTUD1. 1 / 1
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No evidence text available
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Mutated OTUD1 inhibits immune response. 1 / 1
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Our data demonstrate that OTUD1 is involved in maintaining immune homeostasis and loss-of-function mutations of OTUD1 enhance the immune response and are associated with autoimmunity.
OTUD1 activates immune response.
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The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity.
Zinc atom affects OTUD1
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Zinc atom increases the amount of OTUD1. 1 / 1
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Vinclozolin affects OTUD1
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Vinclozolin decreases the amount of OTUD1. 1 / 1
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Valproic acid increases the amount of OTUD1. 1 / 1
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Urethane affects OTUD1
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Urethane increases the amount of OTUD1. 1 / 1
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Triclosan affects OTUD1
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Triclosan increases the amount of OTUD1. 1 / 1
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Sunitinib affects OTUD1
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Sunitinib decreases the amount of OTUD1. 1 / 1
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Sulindac affects OTUD1
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Sulindac increases the amount of OTUD1. 1 / 1
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Schizandrin B increases the amount of OTUD1. 1 / 1
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Rotenone affects OTUD1
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Rotenone decreases the amount of OTUD1. 1 / 1
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Pirinixic acid increases the amount of OTUD1. 1 / 1
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Phenformin affects OTUD1
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Phenformin decreases the amount of OTUD1. 1 / 1
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Nickel sulfate increases the amount of OTUD1. 1 / 1
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Naphthoquinone increases the amount of OTUD1. 1 / 1
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Methyltestosterone increases the amount of OTUD1. 1 / 1
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Methylparaben increases the amount of OTUD1. 1 / 1
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Methylmercury chloride decreases the amount of OTUD1. 1 / 1
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No evidence text available
Methyl methanesulfonate increases the amount of OTUD1. 1 / 1
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Methotrexate decreases the amount of OTUD1. 1 / 1
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Metformin affects OTUD1
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Metformin decreases the amount of OTUD1. 1 / 1
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No evidence text available

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Consistent with the former investigations that IRF3 promoted inflammatory responses in LPS induced sepsis, Otud1 -/- mice were more susceptible to LPS stimulation.
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Indole-3-methanol increases the amount of OTUD1. 1 / 1
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No evidence text available
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Hsa-miR-6761-5p decreases the amount of OTUD1. 1 / 1
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Hsa-miR-570-3p decreases the amount of OTUD1. 1 / 1
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Hsa-miR-543 affects OTUD1
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Hsa-miR-543 decreases the amount of OTUD1. 1 / 1
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Hsa-miR-539-5p decreases the amount of OTUD1. 1 / 1
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Hsa-miR-506-3p decreases the amount of OTUD1. 1 / 1
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No evidence text available
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Hsa-miR-4329 decreases the amount of OTUD1. 1 / 1
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Hsa-miR-4262 decreases the amount of OTUD1. 1 / 1
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Hsa-miR-4251 decreases the amount of OTUD1. 1 / 1
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Hsa-miR-421 affects OTUD1
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Hsa-miR-421 decreases the amount of OTUD1. 1 / 1
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Hsa-miR-3910 decreases the amount of OTUD1. 1 / 1
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Hsa-miR-3714 decreases the amount of OTUD1. 1 / 1
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Hsa-miR-3613-3p decreases the amount of OTUD1. 1 / 1
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Hsa-miR-340-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-335-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-320a decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-26b-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-26a-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-21-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-19a-3p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-192-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-181d-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-181c-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-181b-5p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-124-3p decreases the amount of OTUD1. 1 / 1
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biopax:mirtarbase
No evidence text available
Gentamycin affects OTUD1
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Gentamycin decreases the amount of OTUD1. 1 / 1
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ctd
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Formaldehyde increases the amount of OTUD1. 1 / 1
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ctd
No evidence text available
Ethyl methanesulfonate increases the amount of OTUD1. 1 / 1
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ctd
No evidence text available
Ethanol affects OTUD1
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Ethanol decreases the amount of OTUD1. 1 / 1
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ctd
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Dorsomorphin decreases the amount of OTUD1. 1 / 1
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ctd
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Dibutyl phthalate increases the amount of OTUD1. 1 / 1
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ctd
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Coumestrol affects OTUD1
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Coumestrol decreases the amount of OTUD1. 1 / 1
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ctd
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Copper atom affects OTUD1
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Copper atom increases the amount of OTUD1. 1 / 1
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ctd
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Carbon nanotube decreases the amount of OTUD1. 1 / 1
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ctd
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Avobenzone affects OTUD1
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Avobenzone increases the amount of OTUD1. 1 / 1
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ctd
No evidence text available
Acrylamide affects OTUD1
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Acrylamide decreases the amount of OTUD1. 1 / 1
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ctd
No evidence text available
Tobacco Smoke Pollution increases the amount of OTUD1. 1 / 1
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ctd
No evidence text available
TLR3 affects OTUD1
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TLR3 increases the amount of OTUD1. 1 / 1
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Interestingly, we found that Poly (I : C), a TLR3 signaling stimulator, also induced OTUD1 mRNA expression (XREF_SUPPLEMENTARY).
TGFB affects OTUD1
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TGFB activates OTUD1. 1 / 1
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This latter effect is inhibited by the treatment of SB431542, a selective TbetaRI kinase inhibitor, suggesting that the autocrine TGF-beta is sufficient to promote EMT in OTUD1 depleted cells.
TAZ affects OTUD1
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TAZ inhibits OTUD1. 1 / 1
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In line with this, the transcription of the pluripotency factors NANOG, SOX2, OCT4, and TAZ were significantly elevated in OTUD1 depleted tumors and severely inhibited in tumors expressing wild-type OTUD1.
Soman affects OTUD1
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Soman increases the amount of OTUD1. 1 / 1
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ctd
No evidence text available
SOX2 affects OTUD1
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SOX2 inhibits OTUD1. 1 / 1
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In line with this, the transcription of the pluripotency factors NANOG, SOX2, OCT4, and TAZ were significantly elevated in OTUD1 depleted tumors and severely inhibited in tumors expressing wild-type OTUD1.
SMURF1 affects OTUD1
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SMURF1 activates OTUD1. 1 / 1
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Interestingly, Smurf1 knockdown also remarkably blocked OTUD1 mediated downregulation of both TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG).
POU5F1 affects OTUD1
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POU5F1 inhibits OTUD1. 1 / 1
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In line with this, the transcription of the pluripotency factors NANOG, SOX2, OCT4, and TAZ were significantly elevated in OTUD1 depleted tumors and severely inhibited in tumors expressing wild-type OTUD1.
PCI 5002 affects OTUD1
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PCI 5002 increases the amount of OTUD1. 1 / 1
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ctd
No evidence text available
OTUD1 affects transport
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The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity.
OTUD1 affects sub
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OTUD1 activates sub. 1 / 1
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Similarly, cysteine-to-alanine substitutions in the active sites of Ubp8 and the OTU class DUB, OTUD1, also increase DUB affinity for polyubiquitin (Figs XREF_FIG and XREF_FIG A).
OTUD1 affects protein
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OTUD1 activates protein. 1 / 1
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eidos
OTUD1 interacts with Smurf1 and functions as a deubiquitinase to remove the K48-linked ubiquitination of Smurf1 , prevent its self-ubiquitination degradation , and upregulate its protein level ; whereas the binding of Ndfip1 to MAVS recruits Smurf1 to MAVS , and the interaction between Ndfip1 and Smurf1 enhances the self-ubiquitination ( possibly k63-linked ) and enzyme activity of Smurf1 ( Table 1 ) ( 47 , 49 ) .
OTUD1 affects iron atom
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The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity.

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OTUD1 deficiency impaired CARD9 mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation.
OTUD1 affects creatine
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Among ubiquitin ligases, MURF1, a gene known to target creatine kinase and muscle contractile proteins, and OTUD1 coding for a deubiquitinase protease, were up-regulated in the LM of Met5 pigs.

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Depletion of endogenous OTUD1 potentiated the capacity of RAS transformed MCF10A cells to form tumor organoids in 3D Matrigel but did not inhibit tumor cell survival and proliferation under standard 2D culture conditions.
OTUD1 affects cell growth
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In this process, OTUD1 could remove the K63 linkage ubiquitination of YAP and negatively regulate transcriptional activity and cell growth.
OTUD1 affects cell death
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The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein.
OTUD1 affects VIM
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Modified OTUD1 decreases the amount of VIM. 1 / 1
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As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2, FN1, and VIM.
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OTUD1 directly interacted with Bim and inhibited its ubiquitination .
OTUD1 affects Ubiquitin
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OTUD1 activates mutated Ubiquitin. 1 / 1
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Next, we analyzed the deubiquitination types of Smurf1 mediated by OTUD1 using two ubiquitin mutants, Ub-R48K (all lysines in Ub are mutated to arginines except lysine 48 residue) and Ub-R63K (all lysines in Ub are mutated to arginines except lysine 63 residue).
OTUD1 affects TBK1
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OTUD1 inhibits TBK1. 1 / 1
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These data indicate that OTUD1 inhibits the IFNs antiviral response downstream of MAVS and upstream of TBK1.
OTUD1 affects SMAD
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OTUD1 inhibits SMAD. 1 / 1
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We next investigated the molecular mechanism by which OTUD1 inhibits TGF-beta and SMAD signaling.
OTUD1 affects SKP2
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OTUD1 inhibits SKP2. 1 / 1
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Here, we report that YAP is subject to non proteolytic, K63 linked polyubiquitination by the SCF SKP2 E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1.
OTUD1 affects RIPK1
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OTUD1 inhibits RIPK1. 1 / 1
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When treated with the DUB panel, OTUD1 substantially reduced HMW forms of RIP1, suggesting the prevalence of Lys63 linkages on RIP1.
OTUD1 affects RAS
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OTUD1 activates RAS. 1 / 1
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Depletion of endogenous OTUD1 potentiated the capacity of RAS transformed MCF10A cells to form tumor organoids in 3D Matrigel but did not inhibit tumor cell survival and proliferation under standard 2D culture conditions.
OTUD1 affects PARP1
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OTUD1 activates PARP1. 1 / 1
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Next, we confirmed that OTUD1 overexpression increased the cleavage of caspase-3 and PARP and subsequently increased apoptosis.
OTUD1 affects OTUD6A
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OTUD1 activates OTUD6A. 1 / 1
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Moreover, OTUD1 was not able to increase the enzymatic activity of Aurora-A as much as OTUD6A.
OTUD1 affects IL6
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OTUD1 activates IL6. 1 / 1
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At day 3 after VSV infection, Otud1 -/- mice produced much higher expression of IFNbeta and IL-6 mRNAs (XREF_FIG), and had much lower viral RNAs (XREF_FIG) in their lung tissue than did Otud1 +/+ mice.
OTUD1 affects HRAS
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OTUD1 activates HRAS. 1 / 1
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In line with this, depletion of OTUD1 enhanced the effect of HRAS in MCF10A cells.
OTUD1 affects FN1
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Modified OTUD1 decreases the amount of FN1. 1 / 1
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As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2, FN1, and VIM.
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Here, we report that YAP is subject to non proteolytic, K63 linked polyubiquitination by the SCF SKP2 E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1.
OTUD1 affects DDX58
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Modified OTUD1 increases the amount of DDX58. 1 / 1
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Our data showed that OTUD1 overexpression had no obvious effects on IRF3 and TBK1 protein levels, and increased RIG-I protein levels to some extent (XREF_FIG).
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