OTUD7B Data Analysis

HGNC Gene Name
OTU deubiquitinase 7B
HGNC Gene Symbol
OTUD7B
Identifiers
hgnc:16683 NCBIGene:56957 uniprot:Q6GQQ9
Orthologs
mgi:2654703 rgd:1308111
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for OTUD7B
Number of Papers
66 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 OTUD7Busing 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 OTUD7B 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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OTUD7B deubiquitinates ZAP70. 6 / 6
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Importantly, the Otud7b deficiency substantially enhanced the ubiquitination of Zap70 (XREF_FIG), and the Otud7b knockdown in EL4 cells also enhanced the TCR-CD28-stimulated Zap70 ubiquitination (XREF_FIG).

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OTUD7B has been shown to antagonize ZAP70 ubiquitination, which prevents association with STS1 and STS2.

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Otud7b binds to and deubiquitinates Zap70, thereby preventing the interaction of Zap70 with the negative-regulatory phosphatases, Sts1 and Sts2 199 (XREF_FIG).

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86 A DUB, Otud7b, deubiquitinates ZAP70 to prevent its association with Sts1 and Sts2, thereby positively regulating TCR signaling.

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Otud7b binds to and deubiquitinates Zap70.

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Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination
OTUD7B deubiquitinates TRAF3. 3 / 3
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OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3

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In response to noncanonical NF-kappaB stimuli, Otud7b binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant noncanonical NF-kappaB activation.

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OTUD7B suppresses Smac mimetic-induced lung cancer cell invasion and migration via deubiquitinating TRAF3.
OTUD7B deubiquitinates KLF4. 2 / 2
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These data indicated that OTUD7B interacts with and deubiquitylates KLF4 and OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels.

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As anticipated, co-immunoprecipitation experiments revealed that OTUD7B interacted with and deubiquitylated KLF4.
OTUD7B leads to the deubiquitination of RIPK1. 2 / 2
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OTUD7B, a newly identified member of the A20 family of DUBs, inhibits RIP1 ubiquitination and downstream IKK activity and NF-kappaB signalling [XREF_BIBR].

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USP21 and Cezanne or OTUD7B negatively regulate NFκB signaling by deubiquitinating and inactivating RIP1 upon TNF-α?stimulation, providing a feedback loop in the proinflammatory signaling
OTUD7B deubiquitinates ZAP70 on K544. 2 / 2
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Mechanistically, Otud7b deubiquitinated Zap70 at K544.

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Otud7b likely opposes the action of a Zap70 E3 ligase other than Nrdp1, because Otud7b inhibits Zap70 ubiquitination mainly at K544, which differs from the Nrdp1 target site (K538).
OTUD7B deubiquitinates CDC16. 1 / 1
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Here, we demonstrate that Cezanne/OTUD7B is a cell cycle-regulated DUB that opposes the ubiquitination of APC/C targets.
OTUD7B-C194S deubiquitinates TRAF3. 1 / 1
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The Otud7b mediated TRAF3 deubiquitination required its DUB activity since a catalytically inactive Otud7b mutant, C194S and H358R (CH), failed to deubiquitinate TRAF3 (XREF_FIG).
Modified OTUD7B leads to the deubiquitination of TRAF3. 1 / 1
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The loss of Otud7b promoted anti-CD40-stimulated TRAF3 ubiquitination (XREF_FIG).
OTUD7B-H358R deubiquitinates TRAF3. 1 / 1
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The Otud7b mediated TRAF3 deubiquitination required its DUB activity since a catalytically inactive Otud7b mutant, C194S and H358R (CH), failed to deubiquitinate TRAF3 (XREF_FIG).
OTUD7B leads to the deubiquitination of IKK_complex. 1 / 1
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OTUD7B, a newly identified member of the A20 family of DUBs, inhibits RIP1 ubiquitination and downstream IKK activity and NF-kappaB signalling [XREF_BIBR].
OTUD7B deubiquitinates EGFR. 1 / 1
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USP21 and Cezanne or OTUD7B negatively regulate NFκB signaling by deubiquitinating and inactivating RIP1 upon TNF-α?stimulation, providing a feedback loop in the proinflammatory signaling
Mutated OTUD7B deubiquitinates TRAF3. 1 / 1
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The Otud7b mediated TRAF3 deubiquitination required its DUB activity since a catalytically inactive Otud7b mutant, C194S and H358R (CH), failed to deubiquitinate TRAF3 (XREF_FIG).
OTUD7B leads to the deubiquitination of MLST8. 1 / 1
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In addition, our integrative analysis demonstrates that ubiquitination of MLST8, which is reversed by OTUD7B, is regulated by IRS1/2.
OTUD7B leads to the deubiquitination of NFkappaB. 1 / 1
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OTUD7B, a newly identified member of the A20 family of DUBs, inhibits RIP1 ubiquitination and downstream IKK activity and NF-kappaB signalling [XREF_BIBR].
OTUD7B deubiquitinates RIPK1 on K377. 1 / 1
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OTUD7B deubiquitinates OTUD7B. 1 / 1
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These data indicated that OTUD7B interacts with and deubiquitylates KLF4 and OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels.
OTUD7B deubiquitinates TRAF6. 1 / 1
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Cezanne regulates inflammatory responses to hypoxia in endothelial cells by targeting TRAF6 for deubiquitination
OTUD7B deubiquitinates HIF1A. 1 / 1
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For example, OTU deubiquitinase 7B (OTUD7B) can deubiquitinate HIF-1alpha and inhibit its degradation by the lysosome.
OTUD7B deubiquitinates MAP3K14. 1 / 1
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Given that OTUD7B specifically regulates the NF-kappaB2 pathway and TRAF3 degradation, it would be of interest to determine if OTUD7B also deubiquitinates NIK.
OTUD7B deubiquitinates KDM1A. 1 / 1
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OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis.

Other Statements

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OTUD7B affects NFkappaB
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OTUD7B inhibits NFkappaB.
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In B cells, Otud7b suppresses the activation of noncanonical NF-kappaB signaling by deubiquitinating and stabilizing a negative regulator, TRAF3 201.

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Moreover, OTUD7B negatively regulated NF-kappaB signaling pathway, which may be an effective target for antitumor therapy for HCC.

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Moreover, Overexpression of OTUD7B or TNIP2 indeed antagonizes miR-1180-induced NF-kappaB activation, which further confirmed our conclusion that miR-1180-regulating OTUD7B (or TNIP2) - NF-kappaB- signaling regulation mediates HCC resistance (XREF_FIG and XREF_SUPPLEMENTARY).

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Loss of Cezanne increased transcriptional activity of NF-kappaB (Supplementary Fig S1E) as shown before XREF_BIBR, and also of p53 (Supplementary Fig S1F), suggesting that Cezanne can act as a positive and a negative regulator of transcription factors.

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Cezanne is induced by TNF stimulation and inhibits NF-κB in a negative feedback loop ( xref ).

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Recent studies have suggested that OTUD7B (also known as Cezanne) negatively regulates signal induced noncanonical NF-kappaB pathway activation by deubiquitylating TRAF3.

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Previous studies have shown that OTUD7B inhibited NF-kappaB pathway by deconjugating K63-polyubiquitin chains from RIP-1 and TRAF6, suggesting that it may have roles in inhibition of cancer progression XREF_BIBR, XREF_BIBR.

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Consistently, the WT Otud7b, but not Otud7b CH, suppressed the activation of noncanonical NF-kappaB signaling (XREF_FIG).

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For example, the deubiquitinases Gumby (OTULIN), OTUD7b, and TNFAIP3 (A20) in the OUT family were shown to negatively regulate NFkappaB activation through different mechanisms in different biological contexts [XREF_BIBR - XREF_BIBR].
OTUD7B activates NFkappaB.
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Mutation at these sites disrupted the recruitment of Cezanne to activated TNFR complex and dramatically reduced the inhibition of NF-κB activation by Cezanne.

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The Otud7b deficiency greatly enhanced the NF-kappaB activation by agonistic anti-LTbetaR and anti-CD40 antibodies or BAFF (XREF_FIG), a result that was not due to differential expression of the receptors (XREF_SUPPLEMENTARY).

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Other proteins that modulate NFkappaB signaling were also downregulated, including ubiquitin conjugating enzyme E2 V1 (UBE2V1), which activates NFkappaB, and OTU deubiquitinase 7B (OTUD7B), a clock regulated protein that downregulates the non canonical NF-kappaB pathway.

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Otud7b deficiency in mice has no appreciable effect on canonical NF-kappaB activation but causes hyper-activation of noncanonical NF-kappaB.

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This study sheds light on the molecular mechanism of negative regulation of NF-κB activation by Cezanne.
OTUD7B affects TRAF3
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OTUD7B activates TRAF3.
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OTUD7B activates TRAF3. 6 / 8
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Although the OTU domain of Otud7b preferentially cleaves K11 linked ubiquitin chains in vitro, the Otud7b deficiency in vivo promotes TRAF3 conjugation with K48 ubiquitin chains.

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In addition to being transcriptionally upregulated by NF-kappaB to promote NIK degradation, leading to p100 stabilization and attenuation of non canonical NF-kappaB signalling, TRAF3 is subject to post-translational stabilisation by means of OTUD7B, which targets TRAF3 for deubiquitination of its K48 linked polyubiquitin chains, thereby preventing NIK accumulation and the processing of p100 [XREF_BIBR, XREF_BIBR].

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Otud7b inhibits ubiquitin dependent Traf3 degradation in B cells stimulated through TNF receptor family members, such as BAFF receptor and CD40, and, thereby, negatively regulates noncanonical NF-kappaB signaling and B cell activation.

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OTUD7B increased expression of TRAF3 , leading to a decrease in NIK and processing of p100 to p52 compared to those in the empty vector group ( Fig. 4c ) .

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Likely candidate genes include those encoding TRAF2, TRAF3, the cIAPs or OTUD7B, a de-ubiquitinase that promotes TRAF3 stability.

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Interestingly , we discovered that OTUD7B increases TRAF3 and decreases NIK to inhibit the non-canonical NF-kappaB pathway and that overexpression of OTUD7B suppresses LCL161-induced cell invasion and migration .
OTUD7B inhibits TRAF3.
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OTUD7B inhibits TRAF3. 3 / 3
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We transfected HA-OTUD7B ( WT ) and HA-OTUD7B ( CH ) into H1299 cells and found that OTUD7B ( CH ) decreased the expression of TRAF3 and led to an increase in NIK and processing of p100 to p52 compared to that in the OTUD7B ( WT ) cells ( Fig. 6b ) .

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Because Traf3 deficiency also attenuates TCR signaling, we examined whether Otud7b deficiency promoted the degradation of Traf3 in T cells.

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The de-ubiquitinating enzyme OTUD7B was also shown recently to potentially negatively regulate NF-kappaB2 (and primary B cell activation) by inhibiting activation induced degradation of TRAF3.
OTUD7B affects HIF1A
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OTUD7B activates HIF1A.
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OTUD7B activates HIF1A. 4 / 9
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Our data suggest that Cezanne is essential for HIF-1alpha protein stability and that loss of Cezanne stimulates HIF-1alpha degradation via proteasome independent routes, possibly through chaperone mediated autophagy.

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Overall, these results imply that loss of Cezanne promotes degradation of HIF-1alpha in a proteasome independent manner.

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OTUD7B, also known as Cezanne, deubiquitinates Lys11 linked Ub chains and rescues HIF-1alpha from lysosomal degradation.

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Together, these data suggest that Cezanne does not impact solely on proteasomal degradation of HIF-1alpha, and raise the general question whether the canonical HIF-1alpha degradation machinery is required for Cezanne mediated HIF-1alpha downregulation.
OTUD7B inhibits HIF1A.
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OTUD7B inhibits HIF1A. 1 / 2
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Under low LSS , the activation of NF-kappaB induces elevated HIF-1alpha mRNA and increased the expression of cezanne , a ubiquitin-editing enzyme preventing the HIF-1alpha protein degradation , thus stabilizing HIF-1alpha .
OTUD7B affects MAP3K14
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| 3 6

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In brief , OTUD7B deubiquitinates TRAF3 and inhibits NIK to suppress LCL161-induced lung cancer cell invasion and migration .

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OTUD7B inhibits NIK to suppress LCL161-induced NF-κB pathway activation and cell elongation, invasion and migration.

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In our study, we found that overexpressed OTUD7B inhibits NIK and the non-canonical NF-κB pathway in lung cancer cells by binding to and deubiquitinating TRAF3.

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In brief, OTUD7B deubiquitinates TRAF3 and inhibits NIK to suppress LCL161-induced lung cancer cell invasion and migration.

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OTUD7B inhibits NIK to suppress LCL161-induced NF-κB pathway activation and cell elongation, invasion and migration.

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OTUD7B inhibits NIK to suppress LCL161-induced NF-kappaB pathway activation and cell elongation , invasion and migration .

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In brief, OTUD7B deubiquitinates TRAF3 and inhibits NIK to suppress LCL161-induced lung cancer cell invasion and migration.

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Interestingly , we discovered that OTUD7B increases TRAF3 and decreases NIK to inhibit the non-canonical NF-kappaB pathway and that overexpression of OTUD7B suppresses LCL161-induced cell invasion and migration .

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In our study, we found that overexpressed OTUD7B inhibits NIK and the non-canonical NF-κB pathway in lung cancer cells by binding to and deubiquitinating TRAF3.
OTUD7B affects KLF4
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OTUD7B decreases the amount of KLF4.
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OTUD7B decreases the amount of KLF4. 3 / 3
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OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels.

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We show here that OTUB7B upregulates the level of KLF4 protein, a stem cell pluripotency protein XREF_BIBR, through interacting with and deubiquitylating KLF4, a repressor of VSMC differentiation, whereas OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein level.

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Most importantly, OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels via decreasing its deubiquitylation, whereas decreased KLF4 relieves its repression of transcription of NMHC IIA gene and thus increases NMHC IIA expression levels.
OTUD7B activates KLF4.
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OTUD7B activates KLF4. 3 / 3
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Correspondingly, OTUD7B knockdown decreased, whereas its overexpression increased, KLF4 protein levels.

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Our findings reveal, for the first time, that OTUD7B upregulates the level of KLF4 protein through interacting with and deubiquitylating KLF4.

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Consistently, in HEK293 cells and VSMCs enforced to express OTUD7B and KLF4, OTUD7B overexpression obviously enhanced KLF4 protein stability.
OTUD7B inhibits KLF4.
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OTUD7B inhibits KLF4. 1 / 1
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3) Third, we show for the first time that KLF4 downregulation elicited by Sal-miR-1 and 3 reduced expression of OTUD7B relieves KLF4 repression of the expression of VSMC differentiation genes (e.g. SM alpha-actin, SM22alpha, calponin and SMMHC) and thus increases their expression levels.
OTUD7B increases the amount of KLF4.
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OTUD7B increases the amount of KLF4. 1 / 1
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Further, using loss- and gain-of-function experiments, we confirmed that knockdown of OTUD7B attenuated KLF4 protein levels, whereas the overexpression of OTUD7B had the opposite effect.
E2F1 affects OTUD7B
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E2F1 decreases the amount of OTUD7B. 7 / 7
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OTUD7B stabilizes estrogen receptor alpha and promotes breast cancer cell proliferation.

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Its increased expression has been reported in lung squamous carcinoma and adenocarcinoma compared to normal tissue ; in the same cancer model , OTUD7B promoted cell proliferation , migration and metastasization [ 45 ] .

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Recently, OTUD7B and Cezannehas been reported to deubiquitinate and stabilize the APC/C substrates, as well as promote mitotic progression and cell proliferation.

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These findings collectively identified OTUD7B as an independent predictive factor for the prognosis of non small cell lung cancer and revealed OTUD7B promotes lung cancer cell proliferation and metastasis via Akt and VEGF signal pathway.

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Its increased expression has been reported in lung squamous carcinoma and adenocarcinoma compared to normal tissue; in the same cancer model, OTUD7B promoted cell proliferation, migration and metastasization [XREF_BIBR].

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In addition, OTUD7B depletion significantly decreased ERalpha positive breast cancer cell proliferation and migration.
OTUD7B affects ZAP70
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OTUD7B inhibits ZAP70.
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OTUD7B inhibits ZAP70. 3 / 3
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Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell mediated autoimmune and inflammatory responses.

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Otud7b knockdown in EL4 cells also enhanced the inducible association of Zap70 with Sts1/2 (XREF_FIG).

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Otud7b deficiency attenuated TCR-CD28-stimulated activation of Zap70 and downstream signaling factors and impaired T cell activation and Th1 cell differentiation.
OTUD7B bound to ZAP70 inhibits ZAP70. 1 / 1
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Otud7b binds to and deubiquitinates Zap70, thereby preventing the interaction of Zap70 with the negative-regulatory phosphatases, Sts1 and Sts2 199 (XREF_FIG).
OTUD7B activates ZAP70.
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OTUD7B activates ZAP70. 2 / 2
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Otud7b deficiency promotes the association of Zap70 with Sts1/2.

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Because of the crucial role of Otud7b in regulating the phosphorylation of Zap70, but not Lck, we examined whether Otud7b directly targeted Zap70.
TFDP1 affects OTUD7B
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TFDP1 decreases the amount of OTUD7B. 5 / 5
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F2 affects OTUD7B
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F2 activates OTUD7B.
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F2 activates OTUD7B. 4 / 4
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Importantly, when VSMCs were transfected with Sal-miR-1 and 3 and then treated with thrombin, the upregulation of OTUD7B by thrombin was greatly abolished.

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We first observed that thrombin significantly increased OTUD7B expression both at the protein and mRNA levels in a dose - and time-dependent manner ( Figure 3A-D ) .

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In this study, our results showed that Sal-miR-1 and 3 reduced the upregulation of the OTUD7B mRNA and protein induced by thrombin.

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Importantly , when VSMCs were transfected with Sal-miR-1 and 3 and then treated with thrombin , the upregulation of OTUD7B by thrombin was greatly abolished ( Figure 3E-F ) .
F2 increases the amount of OTUD7B.
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F2 increases the amount of OTUD7B. 1 / 1
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We first observed that thrombin significantly increased OTUD7B expression both at the protein and mRNA levels in a dose- and time dependent manner.
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Depletion of ZA20D1 also reduced SCC invasion, which further suggests that it has additional functions besides antagonising Traf6 (XREF_SUPPLEMENTARY).

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OTUD7B inhibits NIK to suppress LCL161-induced NF-kappaB pathway activation and cell elongation , invasion and migration .

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Further study indicated that Cezanne might inhibit invasion of HCC cells by inducing epithelial-mesenchymal transition (EMT).

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* P < 0.05 OTUD7B inhibits NIK to suppress LCL161-induced NF-kappaB pathway activation and cell elongation , invasion and migration To investigate how OTUD7B inhibits LCL161-induced cell elongation , invasion and migration , we established H1299 cells that overexpressed OTUD7B .
OTUD7B affects Ubiquitin
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Modified OTUD7B decreases the amount of Ubiquitin. 2 / 2
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In contrast, only overexpression of Otubain 1 and Cezanne moderately decreased cellular global Ub conjugate levels, while expression of A20 or Otubain 2 had no effect on total levels of ubiquitinated proteins (Balakirev et al., 2003, Evans et al., 2003, Evans et al., 2004).

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In contrast, only overexpression of mammalian Otubain 1 and Cezanne moderately decreased cellular global Ub conjugate levels, while expression of A20 or Otubain 2 had no effect on total levels of ubiquitinated proteins (Balakirev et al., 2003; Evans et al., 2004; Evans et al., 2003) .
OTUD7B decreases the amount of Ubiquitin. 2 / 2
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USP21 and Cezanne inhibit TNF-B activation by regulating ubiquitin level of RIPK1 (D'Arcy et al., 2015) .

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USP21 and Cezanne inhibit TNF-κB activation by regulating ubiquitin level of RIPK1 (D'Arcy et al., 2015).
TNF affects OTUD7B
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TNF activates OTUD7B. 2 / 3
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Cezanne is induced by TNF‐alpha in cultured cells leading to down‐regulation of NF‐κB signalling through the deubiquitination and inactivation of RIP1, thereby providing a negative feedback loop in pro‐inflammatory signalling (85).

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Cezanne is induced by TNF-alpha in cultured cells leading to down-regulation of NF-jB signalling through the deubiquitination and inactivation of RIP1, thereby providing a negative feedback loop in pro-inflammatory signalling (85) .
OTUD7B affects mTORC2
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OTUD7B activates mTORC2. 3 / 3
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As such it would be expected that both CUL4B-DDB1 and TRAF2 enhance mTORC1 dependent S6K and 4E-BP1 phosphorylation while UCH-L1 and OTUD7B enhance mTORC2 dependent AKT phosphorylation at S473.mTOR si[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Given that binding of p110alpha subunit to Ras and subsequent activation of PI3K is required for the development and maintenance of Kras driven lung tumours XREF_BIBR, XREF_BIBR, we further assessed whether Otud7b promoted mTORC2 and Akt signalling is causally related to Kras induced lung tumorigenesis.

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Pathologically, OTUD7B mediated activation of mTORC2 and AKT signalling may be a critical molecular event down-stream of the RAS and PI3K pathway to favour Kras LA2 -driven lung tumorigenesis, suggesting that OTUD7B may be a potential therapeutic target against diseases harbouring hyperactivated PI3K and mTOR signalling such as cancer.

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In vascular endothelial cells, OTUD7B could reduce inflammation and injury in response to ischemia-reperfusion XREF_BIBR.

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OTUD7B reduces inflammation and injury in response to ischemia-reperfusion by suppressing tumor necrosis factor receptor-associated factor 6 ( TRAF6 ) polyubiquitination 48 .

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In vascular endothelial cells , OTUD7B could reduce inflammation and injury in response to ischemia-reperfusion 45 .
OTUD7B affects MAPK
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OTUD7B activates MAPK. 3 / 3
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Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

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As TRAF3 is dispensable for the activation of canonical NF-kappaB and MAPK signaling OTUD7B does not affect these pathways.

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This prevents miR-137 from binding and suppressing OTUD7B mRNA, resulting in OTUD7B dependent activation of the EFGR and MAPK pathway.
OTUD7B affects AKT
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OTUD7B activates AKT. 2 / 3
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OTUD7B mediated cleavage of K63 linked polyubiquitin chains on GbetaL appears to be a common mechanism to promote mTORC2 and AKT signalling, as knockdown of OTUD7B downregulated AKT (pS473) and conferred chemosensitivity to cancer cells with elevated mTORC2 and AKT signalling due to oncogenic events such as PTEN deletion, PIK3CA, EGFR or KRAS mutations (XREF_FIG).

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In support of a physiologically pivotal role for OTUD7B in the activation of mTORC2 and AKT signalling, genetic deletion of Otud7b in mice suppresses Akt activation and Kras driven lung tumorigenesis in vivo.
FOXO4 affects OTUD7B
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FOXO4 decreases the amount of OTUD7B. 3 / 3
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COP1 knockdown stabilizes Sox2 and prevents differentiation, while OTUD7B knockdown destabilizes Sox2 and induces differentiation.

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Otud7b mediates T cell activation and differentiation in vitro.

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Otud7b deficiency attenuated TCR-CD28-stimulated activation of Zap70 and downstream signaling factors and impaired T cell activation and Th1 cell differentiation.
Vasotocin affects OTUD7B
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As shown in Fig. 5d , AVT also decreases Otud4 , Otud5 and Otud7b in addition to Otub1 / c-Maf .

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XREF_FIG d, AVT also decreases Otud4, Otud5 and Otud7b in addition to Otub1 and c-Maf.
Phenylmercury acetate increases the amount of OTUD7B. 2 / 2
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Hsa-miR-95-5p decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-7846-3p decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-6892-5p decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-6878-5p decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-6760-5p decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-658 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-6134 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-6079 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-5703 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-4799-5p decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-4533 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
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Hsa-miR-4516 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-4475 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-4434 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-154-5p decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-107 decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
2 |
Hsa-miR-103a-3p decreases the amount of OTUD7B. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
Entinostat affects OTUD7B
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Entinostat decreases the amount of OTUD7B. 2 / 2
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ctd
No evidence text available

ctd
No evidence text available
Dioxygen affects OTUD7B
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The DUB Cezanne and OTUD7B is itself induced by oxygen deprivation in cultured endothelial cells.
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Bisphenol A increases the amount of OTUD7B. 2 / 2
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ctd
No evidence text available

ctd
No evidence text available
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Benzo[a]pyrene increases the amount of OTUD7B. 2 / 2
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ctd
No evidence text available

ctd
No evidence text available
ZEB1 affects OTUD7B
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ZEB1 decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
TFDP2 affects OTUD7B
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TFDP2 decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
SOX9 affects OTUD7B
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SOX9 decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
PAX4 affects OTUD7B
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PAX4 decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
| 2

reach
Collectively, these findings suggest the intriguing possibility that inhibition of Otud7b may enhance mucosal immunity against C. rodentium infection.

reach
The results described above prompted us to examine whether Otud7b negatively regulates mucosal immunity against infections.
OTUD7B affects VEGF
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OTUD7B activates VEGF. 2 / 2
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Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT and VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma.

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ELISA and tube formation assay revealed OTUD7B promotes VEGF production and angiogenesis.
OTUD7B affects TP53
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OTUD7B inhibits TP53. 2 / 2
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This verified that silencing OTUD7B and RTKN decreased p53 activity, suggesting that these genes encode p53 pathway enhancers.

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XREF_FIG, two members of the OTU family, OTU6B and OTUD7B, significantly suppressed the transcriptional activity of p53.
OTUD7B affects RNF8
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OTUD7B inhibits RNF8. 2 / 2
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To confirm that RNF8 promotes Lys11-linkage ubiquitin modification, we examined whether Cezanne, a DUB that specifically cleaves the Lys11-linkage ubiquitin conjugates, antagonizes the activity of RNF8 in Lys11-linkage ubiquitin modification of chromatin bound proteins.

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To confirm that RNF8 promotes Lys11-linkage Ub modification, we examined whether Cezanne, a DUB that specifically cleaves the Lys11-linkage Ub conjugates (Bremm et al., 2010), antagonizes the activity[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
OTUD7B affects RIPK1
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OTUD7B decreases the amount of RIPK1. 2 / 2
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USP21 and Cezanne inhibit TNF-κB activation by regulating ubiquitin level of RIPK1 (D'Arcy et al., 2015).

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USP21 and Cezanne inhibit TNF-B activation by regulating ubiquitin level of RIPK1 (D'Arcy et al., 2015) .
OTUD7B affects KRAS
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OTUD7B activates KRAS. 2 / 2
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In support of a physiologically pivotal role for OTUD7B in the activation of mTORC2 and AKT signalling, genetic deletion of Otud7b in mice suppresses Akt activation and Kras driven lung tumorigenesis in vivo.

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Second, OTUD7B amplifications were identified in a variety of cancers, including lung cancer, and homozygous deletion of Otud7b in the Kras LA2 lung cancer mouse model inhibited KRAS driven lung tumorigenesis 95.
OTUD7B affects EGFR
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OTUD7B activates EGFR. 1 / 2
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Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.
OTUD7B affects CD4
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OTUD7B activates CD4. 2 / 2
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Indeed, in vitro activated naive Otud7b -/- T cells produced less IL-2, and aged Otud7b deficient mice had increased frequencies and numbers of naive CD4 T cells, whereas those of effector-memory phenotype were decreased.

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However, at an older age (12 mo old), the Otud7b -/- mice had significantly reduced frequency and absolute numbers of memory like T cells and concomitantly increased frequency and numbers of naive T cells in both CD4 + and CD8 + T cell populations (XREF_FIG).
MAZ affects OTUD7B
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MAZ decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
FOXO1 affects OTUD7B
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FOXO1 decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
FOXF2 affects OTUD7B
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FOXF2 decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
E2F4 affects OTUD7B
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E2F4 decreases the amount of OTUD7B. 2 / 2
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biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
Cuprizone affects OTUD7B
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Cuprizone decreases the amount of OTUD7B. 2 / 2
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ctd
No evidence text available

ctd
No evidence text available
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Dorsomorphin increases the amount of OTUD7B.
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Dorsomorphin increases the amount of OTUD7B. 1 / 1
1 |

ctd
No evidence text available
Dorsomorphin decreases the amount of OTUD7B.
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Dorsomorphin decreases the amount of OTUD7B. 1 / 1
1 |

ctd
No evidence text available
OTUD7B affects TCR
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OTUD7B inhibits TCR.
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OTUD7B inhibits TCR. 1 / 1
| 1

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Otud7b deficiency attenuated but did not completely block TCR signaling, consistent with partially impaired T cell activation and recall responses.
OTUD7B activates TCR.
| 1
Mutated OTUD7B activates TCR. 1 / 1
| 1

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In contrast, Otud7b mutants harboring point mutations in its catalytic domain, C194S and H358N (CH), or lacking its N-terminal UBA domain (40-843) failed to rescue the TCR signaling events (XREF_FIG).
| 1 1
| 1

eidos
To investigate whether OTUD7B can inhibit LCL161 induced-invasion and metastasis in vivo , four groups of six mice each were administered 5 x 106 cells by intravenous tail vein injections .
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These findings collectively identified OTUD7B as an independent predictive factor for the prognosis of non small cell lung cancer and revealed OTUD7B promotes lung cancer cell proliferation and metastasis via Akt and VEGF signal pathway.
OTUD7B affects NFKB2
| 1 1
OTUD7B inhibits NFKB2.
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OTUD7B inhibits NFKB2. 1 / 1
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The de-ubiquitinating enzyme OTUD7B was also shown recently to potentially negatively regulate NF-kappaB2 (and primary B cell activation) by inhibiting activation induced degradation of TRAF3.
OTUD7B activates NFKB2.
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OTUD7B activates NFKB2. 1 / 1
| 1

eidos
We transfected HA-OTUD7B ( WT ) and HA-OTUD7B ( CH ) into H1299 cells and found that OTUD7B ( CH ) decreased the expression of TRAF3 and led to an increase in NIK and processing of p100 to p52 compared to that in the OTUD7B ( WT ) cells ( Fig. 6b ) .
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Valproic acid increases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
Urethane affects OTUD7B
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Urethane increases the amount of OTUD7B. 1 / 1
1 |

ctd
No evidence text available
Tungsten affects OTUD7B
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Tungsten decreases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
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Troglitazone decreases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
1 |
Trichloroethene increases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
Thiram affects OTUD7B
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Thiram decreases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
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Testosterone increases the amount of OTUD7B. 1 / 1
1 |

ctd
No evidence text available

sparser
These discoveries coincided with ROS-dependent inhibition of the DUB enzyme Cezanne in our current study.
1 |

ctd
No evidence text available
1 |
Pirinixic acid increases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
1 |
Nickel monoxide decreases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
1 |
Nickel atom decreases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
1 |
Naphthoquinone increases the amount of OTUD7B. 1 / 1
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ctd
No evidence text available
1 |
Midostaurin decreases the amount of OTUD7B. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-939-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-92b-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-92a-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-877-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-8077 decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-8063 decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7977 decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7854-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7850-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7703 decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-767-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-766-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7162-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7160-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6880-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6874-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6860 decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6851-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6849-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6847-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6811-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6771-3p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6721-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6720-5p decreases the amount of OTUD7B. 1 / 1
1 |

biopax:mirtarbase
No evidence text available