IndraLab

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"These findings lead us to suggest that the role of OTUD7B in prostate cancer cells may be linked to autophagy through the modulation of the mTOR signaling pathway.Collectively, our current study demonstrated that OTUD7B knockdown inhibits autophagy through activating AKT/mTOR pathway and positively contributes to the extrinsic apoptosis and proliferation of prostate cancer cell."

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"OTUD7B is associated with poor prognosis and promotes cell proliferation in cancer."

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"Chen et al. reported that OTUD7B promotes proliferation, migration, and invasion by stabilizing N1ICD in pancreatic cancer [20]."

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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 [XREF_BIBR]."

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"OTUD7B interacts with, deubiquitylate, stabilizes estrogen receptor α in a deubiquitylation activity-dependent manner, and promotes breast cancer cell proliferation, resulting in poor prognosis [17]."

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"Cezanne also promotes the proliferation of LUAD cells by stabilizing IGF-1R [16]."

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"32 OTUD7B and MINDY1 could promote breast cancer proliferation by stabilizing ERα in a deubiquitylation activity–dependent manner."

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"In addition, overexpression of OTUD7B promoted cell proliferation, migration, and VM, similar to the effects of an inhibitor of miR-491-5p."

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"The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137."

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"Furthermore, the present study investigated whether OTUD7B inhibits the proliferation and stemness of breast cancer cells by regulating the protein stability of FOXM1."

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"These data indicated that OTUD7B knockdown may suppress the stemness and proliferation of MDA-MB-468 cells."

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"OTUD7B knockdown effectively induced apoptosis and inhibited the proliferation in PC3 cells."

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"In addition, OTUD7B depletion significantly decreased ERalpha positive breast cancer cell proliferation and migration."

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"These results indicated that the functions of OTUD7B in cancer may be cancer dependent.In ERα-positive breast cancer, OTUD7B directly interacts with and stabilizes ERα and knocking down OTUD7B inhibits cell proliferation by promoting ERα degradation (15)."

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"OTUD7B inhibits the proliferation and migration of breast cancer cells [17]."

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"Genetic and Pharmacological OTUD7B Inactivation Suppresses Leukemia Cell Proliferation."

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"We further found OTUD7B also governed various leukemia cell proliferation and 7Bi treatment efficiently reduced leukemia cell proliferation in vitro."

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"These results show that OTUD7B downregulation greatly inhibits cell proliferation and promotes apoptosis in PC3 cells."
OTUD7B affects ZAP70
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OTUD7B binds ZAP70.
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sparser
"This ubiquitination-defective Zap70 mutant was also attenuated in association with Otud7b, consistent with the idea that the Zap70Otud7b interaction might be facilitated by Zap70 ubiquitination ( xref )."

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"In response to TCR-CD28 ligation, Otud7b rapidly bound to Zap70 and inhibited Zap70 ubiquitination."

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"Otud7b binds to and deubiquitinates Zap70."

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"The Otud7b-Zap70 interaction was further confirmed using a transient transfection experiment in which the overexpressed Otud7b strongly associated with Zap70 (XREF_FIG)."

sparser
"In response to TCR signaling, Otud7b was rapidly recruited to Zap70 via a mechanism that required the UBA domain of Otud7b, suggesting the possibility that Otud7b interacted with ubiquitinated Zap70."

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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)."

sparser
"In response to TCR–CD28 ligation, Otud7b rapidly bound to Zap70 and inhibited Zap70 ubiquitination."

sparser
"Interestingly, although Otud7b did not bind Zap70 in resting T cells, these two proteins formed a complex upon TCR–CD28 stimulation ( xref )."

sparser
"The Otud7bZap70 interaction was further confirmed using a transient transfection experiment in which the overexpressed Otud7b strongly associated with Zap70 ( xref )."

sparser
"Domain mapping analyses revealed the requirement of the N-terminal UBA domain of Otud7b for its physical interaction with Zap70 ( xref ), indicating the facilitation of Otud7bZap70 interaction by ubiquitination."
OTUD7B deubiquitinates ZAP70.
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OTUD7B deubiquitinates ZAP70. 7 / 7
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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)."

"<span class="match term0">Otud7b</span> facilitates T cell activation and inflammatory responses by regulating <span class="match term1">Zap70</span> ubiquitination"

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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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"Additional support derived from functional analysis of a Zap-70 deubiquitinating enzyme, Otud7b, that was shown to facilitate Zap-70 activation by deubiquitinating Zap-70, thereby limiting Zap-70—Sts interactions and the Sts-mediated suppression of Zap-70 phosphorylation [31]."

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

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"Otud7b binds to and deubiquitinates Zap70."
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 dephosphorylates ZAP70.
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OTUD7B leads to the dephosphorylation of ZAP70. 5 / 5
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"Because Otud7b deficiency attenuated Zap70 phosphorylation without affecting activation of its upstream kinase Lck, we hypothesized that the enhanced Zap70 ubiquitination in Otud7b -/- T cells might promote the recruitment of a negative regulator to reduce the phosphorylation of Zap70."

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"For example, Otud7b-mediated ZAP70 deubiquitination inhibits the association of ZAP70 with a negative-regulatory phosphatase, Sts1 or Sts2, thereby promoting TCR/CD28-stimulated ZAP70 phosphorylation [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"This possibility is further suggested by our present finding that Otud7b deficiency promotes Zap70 ubiquitination and inhibits Zap70 phosphorylation in both CD4 + and CD8 + T cells."

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"Otud7b deficiency inhibited TCR-CD28-stimulated phosphorylation of Zap70, Akt, and Erks in both naive CD4 + T cells (XREF_FIG) and naive CD8 + T cells (XREF_FIG)."

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"As seen in primary T cells, Otud7b knockdown by shRNA profoundly inhibited the TCR-CD28-stimulated phosphorylation of Zap70, as well as several downstream kinases (XREF_FIG)."
OTUD7B ubiquitinates ZAP70.
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OTUD7B leads to the ubiquitination of ZAP70. 4 / 4
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"For example, Otud7b-mediated ZAP70 deubiquitination inhibits the association of ZAP70 with a negative-regulatory phosphatase, Sts1 or Sts2, thereby promoting TCR/CD28-stimulated ZAP70 phosphorylation [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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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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"We further demonstrated that by deubiquitinating Zap70, Otud7b prevented the association of Zap70 with the phosphatase Sts1/2, thereby facilitating Zap70 phosphorylation and TCR signaling."

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"This possibility is further suggested by our present finding that Otud7b deficiency promotes Zap70 ubiquitination and inhibits Zap70 phosphorylation in both CD4 + and CD8 + T cells."
OTUD7B phosphorylates ZAP70.
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OTUD7B leads to the phosphorylation of ZAP70. 3 / 3
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"For example, Otud7b-mediated ZAP70 deubiquitination inhibits the association of ZAP70 with a negative-regulatory phosphatase, Sts1 or Sts2, thereby promoting TCR/CD28-stimulated ZAP70 phosphorylation [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The aforementioned results suggested that Otud7b might promote Zap70 phosphorylation by limiting its binding by the phosphatases Sts1/2."

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"The aforementioned results suggested that Otud7b might promote Zap70 phosphorylation by limiting its binding by the phosphatases Sts1/2."
OTUD7B inhibits ZAP70.
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OTUD7B inhibits ZAP70. 2 / 2
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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 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."
OTUD7B affects KDM1A
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OTUD7B binds KDM1A.
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sparser
"These data highlight a dose‐limiting transcriptional regulation of genes involved in cell proliferation by OTUD7BLSD1 axis, which might explain why this pathway confers a proliferative advantage in a context‐dependent manner."

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"Using recombinant proteins, we concluded that OTUD7B can directly interact with LSD1 in vitro (Figure xref , Supporting Information)."

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"Taken all together, these results suggest that OTUD7B binds and stabilizes LSD1 via abrogating its ubiquitination‐dependent proteasomal degradation."

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"Therefore, perturbation of OTUD7BLSD1 axis results in changes in both activating and repressive chromatin modification marks, providing a plausible mechanism for altered gene transcription due to OTUD7B loss."

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"We next explored the clinical implications of OTUD7BLSD1 signaling."

No evidence text available

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"Using OLco‐regulated gene sets revealed that loss of OTUD7B or LSD1 resulted in a significantly reduced expression of metastatic genes (Figure xref , Supporting Information), providing potential mechanistic clues explaining suppressed metastatic ability due to impaired OTUD7BLSD1 signaling."

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"2.1 OTUD7B Binds LSD1 and Regulates Its Stability."

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"OTUD7B Binds LSD1 and Regulates Its Stability."

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"In addition to USP22 and USP28, ectopic OTUD7B also bound robustly to endogenous LSD1 (Figure  1A )."
OTUD7B deubiquitinates KDM1A.
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"For example, high OTUD7B expression in breast cancer acts to deubiquitinate LSD1, in turn activating histone deacetylase complexes to promote metastasis through epigenetic effects 19."

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"OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis."

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"As shown in Figure S3A in the Supporting Information, K63R mutation caused significant loss of polyubiquitinated LSD1 signals, whereas K48R displayed very marginal reduction in LSD1 ubiquitination, suggesting LSD1 ubiquitination involves mixed linkage specificity, and predominantly prefers K63‐linked polyubiquitin chains.We next determined whether OTUD7B modulated LSD1 deubiquitination."

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"Conversely, OTUD7B depletion remarkably enhanced polyubiquitination of endogenous LSD1 (Figure 2B)."

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"To assess the types of Ub‐linkage that OTUD7B may catalyze when deubiquitinates LSD1, we utilized two Ub mutants, K48 and K63."

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"Ubiquitin-specific peptidase 7 (USP7) and OTU deubiquitinase 7B (OTUD7B) mediate the deubiquitylation and stability of LSD1, which is crucial for breast cancer invasion and metastasis [ 13 , 14 ]."

"<span class="match term0">OTUD7B</span> is responsible for <span class="match term1">LSD1</span> deubiquitination at K226/277 residues, resulting in dynamic control of <span class="match term1">LSD1</span> binding partner specificity and cellular homeostasis"

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"Therefore, perturbation of OTUD7BLSD1 axis results in changes in both activating and repressive chromatin modification marks, providing a plausible mechanism for altered gene transcription due to OTUD7B loss.To investigate the contribution of LSD1 deubiquitination by OTUD7B in OTUD7B‐mediated LSD1 genomic distribution and H3K4me2/H3K9me2 enrichment, we analyzed LSD1 binding and H3K4me2/H3K9me2 levels of the selected 11 genes in LSD1 reconstituting cells."

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"The OTUD7B is responsible for the deubiquitination of LSD1 at the K226/277 residues, and OTUD7B depletion increases the LSD1 K63‐linked ubiquitination and p62‐mediated proteolysis [40]."
OTUD7B activates KDM1A.
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"The fact that many of these gene hits are linked to cell cycle likely explains the result that the primary functions of OTUD7B or LSD1 in coordinating cell cycle progression.The above ChIP‐seq and RNA‐seq datasets were aligned to explore the potential correlations between OTUD7B‐induced H3K4me2 and LSD1 occupancy changes and changes in gene transcription."

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"Strikingly, the OTUD7B defect promoted the association of LSD1 with p62 and targeted LSD1 for p62-mediated proteasomal degradation, thereby eliminating breast cancer metastasis."

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"Moreover, physiological fluctuation of OTUD7B modulates cell cycle-dependent LSD1 oscillation, ensuring the G1/S transition."

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"We first asked if CoREST is required for OTUD7B‐mediated LSD1 stabilization."

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"19 Strikingly, p62 knockdown completely blunted LSD1 degradation triggered by OTUD7B or CoREST loss (Figure  4A ,B)."
OTUD7B inhibits KDM1A.
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"OTUD7B or CoREST depletion only resulted in LSD1 degradation in p62 cells, but not in p62 cells (Figure 4E), suggesting that the binding to poly‐Ub chains on LSD1 is indispensable for p62‐mediated LSD1 degradation triggered by the deficiency of OTUD7B or CoREST.We next determined the type of poly‐Ub chains predisposed LSD1 to p62 binding."

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"We next generated OTUD7B reconstituting cell lines by expressing sgRNA‐resistant WT or mutant OTUD7B construct in MDA‐MB‐231 cells depleted of OTUD7B, and found only WT OTUD7B reconstitution rescued LSD1 decrease, excluding a possible off‐target issue during sgRNA‐mediated knockdown, also suggesting the DUB catalytic function of OTUD7B is required for its regulation of LSD1 (Figure 1F)."

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"The OTUD7B is responsible for the deubiquitination of LSD1 at the K226/277 residues, and OTUD7B depletion increases the LSD1 K63‐linked ubiquitination and p62‐mediated proteolysis [40]."
OTUD7B ubiquitinates KDM1A.
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"Collectively, these results demonstrate that K63‐linked ubiquitination of LSD1, triggered by depletion of OTUD7B or CoREST, targets LSD1 to proteasomal degradation via p62.The enhanced interaction between p62 and LSD1 upon OTUD7B loss raised one possibility that p62 may compete with CoREST for binding to ubiquitinated LSD1."

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"In cells expressing K63R Ub mutant, OTUD7B‐depletion failed to increase LSD1 ubiquitination (Figure 2C)."
OTUD7B increases the amount of KDM1A.
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"As described earlier, in OTUD7B‐dificient cells, WT OTUD7B reconstitution fully restored LSD1 protein expression."
OTUD7B decreases the amount of KDM1A.
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"Conversely, OTUD7B depletion in several breast cancer cell lines profoundly decreased LSD1 protein level, without affecting LSD1 mRNA expression (Figure 1E)."
OTUD7B affects TRAF3
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OTUD7B binds TRAF3.
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"Non-canonical NF-κB activators induce the interaction of OTUD7B and TRAF3, thereby down-regulating TRAF3 ubiquitination and degradation and preventing aberrant non-canonical NF-κB activation."

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"Mechanistically, OTUD7b binds to TRAF3 and deubiquitinates it in a signal-dependent manner."

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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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"Non-canonical NF-κB activators induce the interaction of OTUD7B and TRAF3, thereby down-regulating TRAF3 ubiquitination and degradation and preventing aberrant non-canonical NF-κB activation."

No evidence text available

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"We found that Traf3 physically interacted with Otud7b in T cells (unpublished data), although we could not detect appreciable degradation of Traf3 along with TCR-CD28 ligation in either WT or Otud7b deficient T cells."

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"OTUD7B functions as an inhibitor of the noncanonical NF-κB pathway by deubiquitinating TNF receptor-associated Factor 3 (TRAF3) [8]."

No evidence text available

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"Activation of BAFFR increases OTUD7B expression and the newly synthesized deubiquitinase then binds to TRAF3 resulting in the formation of a high molecular weight complex including OTUDB7, TRAF3, TRAF2, and cIAP1/2."

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"Mechanistically, OTUD7b binds to TRAF3 and deubiquitinates it in a signal-dependent manner."
OTUD7B activates TRAF3.
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eidos
"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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"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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"For instance, OTUD7B functions to prevent TRAF3 degradation in lung cancer cell cells, suppressing their invasiveness though the non-canonical NF-κB pathway 23."

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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 these cancers, the upregulation of OTUD7B promotes the stabilization and activation of TRAF3, estrogen receptor α, and N1ICD, leading to uncontrolled cell growth and tumor formation [31,32,33,34,35,36]."

eidos
"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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"Likely candidate genes include those encoding TRAF2, TRAF3, the cIAPs or OTUD7B, a de-ubiquitinase that promotes TRAF3 stability."
OTUD7B deubiquitinates TRAF3.
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OTUD7B deubiquitinates TRAF3. 4 / 4
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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."

"<span class="match term0">OTUD7B</span> controls non-canonical NF-kappaB activation through deubiquitination of <span class="match term1">TRAF3</span>"

trips
"OTUD7B suppresses Smac mimetic-induced lung cancer cell invasion and migration via deubiquitinating TRAF3."

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"Accumulation of NIK induces phosphorylation of the inhibitor of kappa-B kinase α (IKKα), leading to the ubiquitination and processing of p100.19 20 21 56 The inactive precursor protein p100 undergoes proteasome-mediated processing to generate active protein p52, which binds to RelB and translocates to the nucleus.19 20 21 The deubiquitination of TRAF3 by Otud7b inhibits NF-κB activation by preventing TRAF3 proteolysis and NIK accumulation.56 Alternatively, the canonical pathway relies on ubiquitination of RIP1 kinase or TRAF6."
OTUD7B inhibits TRAF3.
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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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"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."
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"We found that Cezanne overexpression in NRCMs activated AKT/mTOR to reduce apoptosis, autophagy and oxidative stress; this mechanism of Cezanne was also verified in animal experiments."

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"OTUD7B (Cezanne) prevents tumor necrosis factor (TNF)-induced apoptosis of dendric cells in infection (Harit et al. 2023) and facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination (Hu et al. 2016)."

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"Western blot indicated that AAV9-Cezanne decreased the ratio of Bax to Bcl-2 and further confirmed that Cezanne could inhibit cardiomyocyte apoptosis ( Fig. 6 D)."

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"These results indicated that OTUD7B knockdown promoted apoptosis in PC3 cells."

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"OTUD7B knockdown effectively induced apoptosis and inhibited the proliferation in PC3 cells."

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"Our animal experiments revealed that Cezanne overexpression in mice reversed DOX-induced cardiomyocyte apoptosis, autophagy, oxidative stress and hypertrophy."

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"Taken together, OTUD7B promotes the proliferation, and autophagy, and inhibits apoptosis of prostate cancer cells via the AKT/mTOR signaling pathway."

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"OTUD7b stabilizes TRAF2 by cleaving K48-linked polyubiquitin chains and prevents DC apoptosis."

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"16 , 17 Molecularly, OTUD7B inhibits LCL161 inhibitor of apoptosis protein antagonist‐induced invasion and migration by binding to and deubiquitinating TRAF3 (tumor necrosis factor receptor‐associated factor 3), thereby inhibiting NIK (NF‐κB‐inducing kinase) and preventing noncanonical NF‐κB activation in lung cancer."

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"Therefore, we transfected Ad-shCezanne to knock down Cezanne levels and found that Cezanne knockdown significantly promoted DOX-induced apoptosis in NRCMs via Western blot ( Fig. 3 A)."
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"In good agreement, DC-specific ablation of OTUD7b induced apoptosis of DCs, prevented the induction of pathogenic CD8 T cells and completely protected from ECM."

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"As shown in Fig. 5 C, PI3K/AKT blockage significantly abolished the effect of Cezanne in DOX-induced apoptosis and autophagy as confirmed by Western blot, which showed that in the DOX + Av-Cezanne + H[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"This study represents one of several reports showing both negative and positive effects of OTUD7B on tumor cell invasiveness 18, 23, 42, 63, a tumorigenic phenotype which we have not addressed here.We further observed one of the major outcomes associated with the stabilization of p53 via enforced OTUD7B expression involved inducing HCC cell apoptosis, phenocopying the p53 response to cellular insults such as unresolved levels of DNA damage."

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"And consistent with OTUD7B-induced apoptosis mainly proceeding through the mitochondrial-dependent pathway, cytochrome c (CYCS) release from mitochondria to the cytoplasm was evident in cells following the overexpression of OTUD7B (Figure 7E)."

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"This illustrates a conserved function of OTUD7b for the prevention of TNF-induced apoptosis in human and murine DCs."

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"OTUD7B promotes apoptosis of hepatocellular carcinoma cells through p53."

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"OTUD7B knockdown inhibits cell proliferation and induces apoptosis in PC3 cells."

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"The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2."

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"These findings lead us to suggest that the role of OTUD7B in prostate cancer cells may be linked to autophagy through the modulation of the mTOR signaling pathway.Collectively, our current study demonstrated that OTUD7B knockdown inhibits autophagy through activating AKT/mTOR pathway and positively contributes to the extrinsic apoptosis and proliferation of prostate cancer cell."

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"Moreover, previous research reported that OTUD7B promotes apoptosis in liver cancer cells by negatively regulating NF-κB 24."
OTUD7B affects KLF4
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OTUD7B binds KLF4.
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"An immunoprecipitation-mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Kruppel-like factor 4)."

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"Therefore, the interaction between OTUD7B and KLF4 was investigated further."

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"Therefore, the interaction between OTUD7B and KLF4 was investigated further."

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"Series of OTUD7B and KLF4 fragments were constructed to further investigate the binding domains required for interaction between OTUD7B and KLF4."

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"A region of OTUD7B (amino acid [aa] 151–aa446) and a region of KLF4 (aa200–aa397) were required for OTUD7B to bind to KLF4 (Figure  xref )."

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"Series of OTUD7B and KLF4 fragments were constructed to further investigate the binding domains required for interaction between OTUD7B and KLF4."

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"In the further study, we utilized co-immunoprecipitation experiments to examine the interaction of OTUD7B with KLF4 and found that KLF4 was co-immunoprecipitated by anti-OTUD7B antibody."

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"The specificity of their interaction was verified by increased association of OTUD7B with KLF4 in OTUD7B-overexpressed cells (Figure xref G)."

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"As anticipated, co-immunoprecipitation experiments revealed that OTUD7B interacted with and deubiquitylated KLF4."

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"An immunoprecipitation–mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel‐like factor 4)."
OTUD7B activates KLF4.
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"Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site-linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway."

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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 deubiquitinates KLF4.
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"Du et al. reported that OTUD7B attenuates cardiac hypertrophy by inhibiting KLF4 ubiquitination and degradation [20]."

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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 decreases the amount of KLF4.
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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."

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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."
OTUD7B inhibits KLF4.
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"Notably, OTUD7B suppressed CH progression by activating AKT signaling cascades and regulating KLF4 (Krüppel‐like factor 4) degradation."

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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 ubiquitinates KLF4.
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"Reversely, OTUD7B overexpression in 293A cells markedly reduced the accumulation of ubiquitylated KLF4, whereas its knockdown had an opposite effect."
OTUD7B increases the amount of KLF4.
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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."
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."

reach
"NF-kappaB is activated by Otud7b deficiency."

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

reach
"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."

reach
"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)."

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

reach
"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."

eidos
"Thus although hypoxia primed cells for inflammatory activation it simultaneously induced Cezanne which impeded signalling to NF-kappaB by suppressing TRAF6 ubiquitination ."

reach
"Using RNA-sequencing and bioinformatics analysis followed by a luciferase reporter assay, we found that Otud7b downregulates NF-kappaB activity."
OTUD7B activates NFkappaB.
| 4 2
| 4 2

reach
"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."

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

reach
"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)."

sparser
"Mutation at these sites disrupted the recruitment of Cezanne to activated TNFR complex and dramatically reduced the inhibition of NF-κB activation by Cezanne."

sparser
"This study sheds light on the molecular mechanism of negative regulation of NF-κB activation by Cezanne."

reach
"DC-specific OTUD7b augments NF-kappaB and MAP kinase signaling by stabilizing TRAF2."
OTUD7B affects LEF1
2 | 14 6
OTUD7B binds LEF1.
2 | 4 6
2 | 3 6

sparser
"OTUD7B and LEF1 interact with each other through the UBA and HMG domains, respectively."

sparser
"LEF1 Interacts with OTUD7B through the HMG and UBA Domains, Respectively."

sparser
"The interaction between LEF1 and OTUD7B occurs through the HMG and UBA domains of LEF1 and OTUD7B, respectively."

sparser
"To determine which domains are responsible for the interaction between LEF1 and OTUD7B, we generated three deletion mutants of LEF1: LEF1ΔHMG (High Mobility Group domain deleted, aa 1-804), LEF1ΔCRD (context-dependent regulatory domain deleted, aa 1-201 & 805-1116), and LEF1ΔBCBD (β-catenin binding domain deleted, aa 202-1116) ( xref A) using the MYC-LEF1 plasmid."

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reach
"To determine which domains are responsible for the interaction between LEF1 and OTUD7B, we generated three deletion mutants of LEF1: LEF1ΔHMG (High Mobility Group domain deleted, aa 1-804), LEF1ΔCRD (context-dependent regulatory domain deleted, aa 1-201 & 805-1116), and LEF1ΔBCBD (β-catenin binding domain deleted, aa 202-1116) (Figure 2A) using the MYC-LEF1 plasmid."

reach
"This result suggests that LEF1 binds to OTUD7B through its N-terminus, which contains the UBA domain."

sparser
"As shown in xref D, the full-length OTUD7B and all three mutant forms interacted with LEF1."

sparser
"This result suggests that LEF1 binds to OTUD7B through its N-terminus, which contains the UBA domain."
OTUD7B binds LEF1 and HMG domain. 1 / 1
| 1

reach
"This result demonstrates that OTUD7B binds to LEF1 through its HMG domain."
OTUD7B activates LEF1.
| 5
OTUD7B activates LEF1. 5 / 5
| 5

reach
"Furthermore, OTUD7B promotes the nuclear localization of LEF1, leading to an increased interaction with beta-catenin in the nucleus while not noticeably affecting ubiquitination on LEF1."

reach
"Compared to FOPflash luciferase levels, both USP36 and OTUD7B increased the luciferase activities (TOPflash), but OTUD7B significantly enhanced LEF1 activity to a greater extent (6.64-fold) than USP36 did (2.04-fold) (Figure 1C)."

reach
"Figure 1D demonstrates that the loss of OTUD7B significantly suppressed LEF1 activity."

reach
"As a result, we hypothesized that OTUD7B promotes Wnt signaling by facilitating the nuclear localization of LEF1 and/or its interaction with β-catenin within the nucleus."

reach
"The reason for caution lies in the catalytic-independent function of OTUD7B in activating LEF1."
OTUD7B deubiquitinates LEF1.
| 4
OTUD7B deubiquitinates LEF1. 4 / 4
| 4

reach
"As shown in Figure 3, OTUD7B did not noticeably deubiquitinate LEF1, and its protein stability was not affected by OTUD7B."

reach
"Despite its interaction with LEF1 and enhancement of Wnt signaling activity, it was surprising that OTUD7B did not deubiquitinate LEF1 or affect its protein stability."

reach
"OTUD7B Does Not Deubiquitinate nor Stabilize LEF1."

reach
"Since LEF1 is targeted for proteasomal degradation through ubiquitination by multiple E3 ligases, including NARF and Pja2 [19,20], we investigated whether OTUD7B deubiquitinates LEF1 and regulates its protein stability."
OTUD7B increases the amount of LEF1.
| 1
OTUD7B increases the amount of LEF1. 1 / 1
| 1

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"As shown in Figure 4B, OTUD7B induced a 4.82-fold increase in the β-catenin-bound LEF1 levels in the nucleus, while the nuclear LEF1 levels were only increased by 38% at this time."
OTUD7B affects autophagy
| 19
OTUD7B activates autophagy.
| 15
| 15

reach
"Overall, our results suggest that OTUD7B knockdown reduces autophagy by activating AKT/mTOR signaling in PC3 cells."

reach
"Cezanne promoted autophagy through PIK3C3 stabilization and PIK3C2A transcription in lung adenocarcinoma."

reach
"OTUD7B knockdown inhibits proliferation and autophagy through AKT/mTOR signaling pathway in human prostate cancer cell."

reach
"As Cezanne could activate cell autophagy, in our study, in low- and high-Cezanne expression cells, we compared the EGFR recycling speed by focusing on the EGFR location in cells."

reach
"The results showed that under Rapamycin stimulation, PIK3C3 or PIK3C2A knockdown reversed the autophagy activation induced by Cezanne, and the knockdown of both would be more remarkable (Fig. 6E, F)."

reach
"Third, Cezanne was reported to regulate the stability of p62 [44], so in this study, we did not show the results of p62.In conclusion, this study showed a new network connecting Cezanne, autophagy, and Osimertinib resistance, and in consideration of the wide effect and complexity of autophagy, further study is needed to explore the effect of autophagy induced by Cezanne on other cellular functions."

reach
"OTUD7B knockdown inhibited autophagy through AKT/mTOR signaling."

reach
"To identify the underlying mechanism, we speculated that OTUD7B knockdown inhibits autophagy via the AKT/mTOR signaling pathway in PCa cells."

reach
"Taken together, OTUD7B promotes the proliferation, and autophagy, and inhibits apoptosis of prostate cancer cells via the AKT/mTOR signaling pathway."

reach
"As shown in Fig. 5 C, PI3K/AKT blockage significantly abolished the effect of Cezanne in DOX-induced apoptosis and autophagy as confirmed by Western blot, which showed that in the DOX + Av-Cezanne + H[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B inhibits autophagy.
| 4
| 4

reach
"Our animal experiments revealed that Cezanne overexpression in mice reversed DOX-induced cardiomyocyte apoptosis, autophagy, oxidative stress and hypertrophy."

reach
"We found that Cezanne overexpression in NRCMs activated AKT/mTOR to reduce apoptosis, autophagy and oxidative stress; this mechanism of Cezanne was also verified in animal experiments."

reach
"Subsequent functional experiments found that Cezanne knockdown in NRCMs promoted DOX-induced apoptosis, autophagy and oxidative stress, while Cezanne overexpression protected NRCMs from these damages [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Consistent with the data in vitro , the Western blot results showed that autophagy dysregulation was reversed by AAV9- Cezanne injection, confirmed by the decrease of ATG5 and LC3Ⅱ and the increase of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
UBC affects OTUD7B
18 1 |
18 1 |

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OTUD7B affects TP53
| 12 6
OTUD7B binds TP53.
| 4 6
| 3 6

sparser
"Furthermore, given both HepG2 and SMMC-7721 cells are known to express wildtype (WT) p53, it was important to determine if p53 mutations which are prevalent in HCC affect OTUD7B-p53 interactions."

sparser
"Others have shown retinoic acid (RA) treatment increases OTUD7B levels in HCC xref while we observed that OTUD7B was subject to transcriptional repression by p53: the latter finding further suggests that p53 establishes negative feedback towards tuning the cellular levels of OTUD7B. It is further noteworthy to consider how the wiring of the OTUD7B-p53 relationship may dovetail with the well-known Mdm2-p53 regulatory circuit."

sparser
"Clinical data analysis showed a positive correlation between OTUD7B and p53 protein levels in HCC tissues, suggesting that the OTUD7B-p53 axis may represent a potential therapeutic target for HCC xref ."

reach
"Thus, OTUD7B physically associates with p53 through dual interfaces within the p53 TAD (1-60) and DBD (98-292) regions.Additional characterization using nuclear-cytoplasmic separation showed a biased distribution of OTUD7B within the cytoplasm of HCC cells while p53 occurred both in the cytoplasm and nucleus (Figure 1I)."

reach
"Furthermore, given the observation that OTUD7B binds mutant forms of p53, it was relevant to examine the capability of OTUD7B to deubiquitinate mutant p53."

sparser
"Moreover, interactions between the endogenous OTUD7B and p53 proteins were demonstrable in HepG2 cells (Figure xref F)."

sparser
"Further mapping experiments were then conducted using a range of p53 deletion constructs (Figure xref G) towards defining the regions of interaction between OTUD7B and p53."

sparser
"Thus, OTUD7B physically associates with p53 through dual interfaces within the p53 TAD (1-60) and DBD (98-292) regions."

reach
"Further mapping experiments were then conducted using a range of p53 deletion constructs (Figure 1G) towards defining the regions of interaction between OTUD7B and p53."
OTUD7B binds mutated TP53. 1 / 1
| 1

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"IP experiments in MHCC-97H (harboring R249S TP53) and Huh7 (harboring Y220C TP53) cells confirmed interactions between endogenous OTUD7B and mutant p53 (Figure 1K)."
OTUD7B inhibits TP53.
| 3
OTUD7B inhibits TP53. 3 / 3
| 3

reach
"XREF_FIG, two members of the OTU family, OTU6B and OTUD7B, significantly suppressed the transcriptional activity of p53."

reach
"Thus, addressing the diminished OTUD7B levels in HCC would notionally restore p53 expression and function whereas targeting OTUD7B could help eliminate the effects of p53 GOF mutants."

reach
"This verified that silencing OTUD7B and RTKN decreased p53 activity, suggesting that these genes encode p53 pathway enhancers."
OTUD7B increases the amount of TP53.
| 2
OTUD7B increases the amount of TP53. 2 / 2
| 2

reach
"Supporting this possibility, the silencing of OTUD7B expression in HCC cells using two independent shRNAs resulted in the downregulation of p53 protein levels (Figure 2A) whereas the ectopic expression of OTUD7B increased p53 protein levels (Figure 2B)."

reach
"Interestingly, the regulatory effect of OTUD7B on p53 was not limited to HCC since, for example, the same phenomenon was observed in HeLa cervical cancer cells where silencing OTUD7B similarly decreased p53 protein levels (Figure 2D)."
OTUD7B deubiquitinates TP53.
| 2
OTUD7B leads to the deubiquitination of mutated TP53. 1 / 1
| 1

reach
"Lastly, the results of in vitro de-ubiquitination assays showed that the presence of recombinant OTUD7B purified from E. coli was sufficient to significantly reduce ubiquitination levels in wildtype and p53 mutants (Figure 4F)."
OTUD7B deubiquitinates TP53. 1 / 1
| 1

reach
"Together this indicates that OTUD7B deubiquitinates p53 to reduce its overall polyubiquitination levels."
OTUD7B activates TP53.
| 1
OTUD7B activates TP53. 1 / 1
| 1

reach
"OTUD7B promotes p53 transcriptional activity."
OTUD7B affects SQSTM1
3 | 12 3
OTUD7B deubiquitinates SQSTM1.
| 8
OTUD7B deubiquitinates SQSTM1. 8 / 8
| 8

reach
"OTUD7B/Cezanne (OTU deubiquitinase 7B) acts as a negative regulator of antiviral immunity by deubiquitinates SQSTM1/p62 and promotes IRF3 degradation [232]."

reach
"OTUD7B/Cezanne (OTU deubiquitinase 7B) acts as a negative regulator of antiviral immunity by deubiquitinates SQSTM1/p62 and promotes IRF3 degradation [232]."

reach
"Moreover, OTUD7B negatively regulates antiviral immunity by deubiquitinating p62, promoting IRF3 autophagic degradation and balancing type I interferon signaling during viral infection [16]."

reach
"With respect to viral infection, in vitro studies revealed that OTUD7b impairs innate anti-viral immunity in macrophages by deubiquitinating SQSTM1/p62 during vesicular stomatitis virus infection [58]."

reach
"For example, the cell growth-regulating nucleolar protein LYAR suppresses IFN production by targeting phosphorylated IRF3 [13], OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to inhibit antiviral immunity [14], and the prolyl isomerase PIN1 negatively regulates the innate antiviral response by proteasome-dependent degradation of IRF3 [15]."

reach
"For example, the cell growth-regulating nucleolar protein LYAR suppresses IFN production by targeting phosphorylated IRF3 [13], OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to inhibit antiviral immunity [14], and the prolyl isomerase PIN1 negatively regulates the innate antiviral response by proteasome-dependent degradation of IRF3 [15]."

reach
"OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to regulate antiviral immunity."

reach
"OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to regulate antiviral immunity."
OTUD7B binds SQSTM1.
3 | 1
3 | 1

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sparser
"LSD1 protein expression oscillates during cell cycle, low in G1 and high in G2/M. [ xref ] Similar expression patterns were observed with OTUD7B. [ xref ] We therefore set out to investigate if OTUD7Bp62 axis is responsible for LSD1 ubiquitination and degradation throughout the cell cycle."
OTUD7B ubiquitinates SQSTM1.
| 3
OTUD7B ubiquitinates SQSTM1. 3 / 3
| 3

reach
"With respect to viral infection, in vitro studies revealed that OTUD7b impairs innate anti-viral immunity in macrophages by deubiquitinating SQSTM1/p62 during vesicular stomatitis virus infection [58]."

reach
"Moreover, OTUD7B negatively regulates antiviral immunity by deubiquitinating p62, promoting IRF3 autophagic degradation and balancing type I interferon signaling during viral infection [16]."

reach
"With respect to viral infection, in vitro studies revealed that OTUD7b impairs innate anti-viral immunity in macrophages by deubiquitinating SQSTM1/p62 during vesicular stomatitis virus infection [58]."
OTUD7B activates SQSTM1.
| 1 2
OTUD7B activates SQSTM1. 3 / 3
| 1 2

sparser
"OTUD7B directly interacts with IRF3 and activates p62 by removing K63 polyubiquitin chains leading to enhanced p62 oligomerization."

sparser
"The deubiquitinating enzyme OTUD7B activates IRF3-associated SQSTM1 by removing its K63-linked polyubiquitin chains, leading to the increased activation of SQSTM1 to promote IRF3 degradation [ 13 ]."

reach
"Strikingly, the OTUD7B defect promoted the association of LSD1 with p62 and targeted LSD1 for p62-mediated proteasomal degradation, thereby eliminating breast cancer metastasis."
OTUD7B affects HIF1A
1 | 1 5 3
OTUD7B activates HIF1A.
| 4
OTUD7B activates HIF1A. 4 / 9
| 4

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

reach
"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."

reach
"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."

reach
"Overall, these results imply that loss of Cezanne promotes degradation of HIF-1alpha in a proteasome independent manner."
OTUD7B binds HIF1A.
1 | 3
1 | 3

sparser
"These findings support the interaction between OTUD7B and HIF-1α ( xref )."

sparser
"HA-HIF-1α co-immunoprecipitated with FLAG-OTUD7B, while the reciprocal Co-IP also confirmed the association of HIF-1α with OTUD7B. These findings definitively established the interaction between OTUD7B and HIF-1α ( xref )."

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sparser
"Next, Co-IP assays were performed to evaluate the interactions between the endogenous OTUD7B and HIF-1α."
OTUD7B inhibits HIF1A.
| 1
OTUD7B inhibits HIF1A. 1 / 2
| 1

eidos
"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 deubiquitinates HIF1A.
| 1
OTUD7B deubiquitinates HIF1A. 1 / 1
| 1

reach
"For example, OTU deubiquitinase 7B (OTUD7B) can deubiquitinate HIF-1alpha and inhibit its degradation by the lysosome."
OTUD7B affects Ad
| 16
| 16

sparser
"After 24 h, Ad-Cezanne and Ad-shCezanne without GFP labelling were also transfected into cells, followed by 24 h treatment of DOX (1 μM)."

sparser
"The stock solutions of Ad-OTUD7B and Ad-v were at concentrations of 1.58 × 10 10 and 4.00 × 10 10 plaque formation units (PFUs)/ml, respectively."

sparser
"At the same time, adenovirus overexpressing Cezanne (Ad-Cezanne) was also constructed with Ad-v as a control."

sparser
"Caspase-3 activity assay also confirmed that Ad-Cezanne could inhibit DOX-induced apoptosis while Ad-shCezanne exacerbated the phenomenon."

sparser
"Adenovirus based on the pDC315-EGFP vector carrying OTUD7B (Ad-OTUD7B) and corresponding control (Ad-v) were synthesized by Hanbio Biotechnology, China."

sparser
"Ad-OTUD7B and Ad-v were propagated in HEK293 cells."

sparser
"Furthermore, we overexpressed OTUD7B by transfecting CFs with adenovirus, and the transfection efficiency is shown in Fig. 4 A. Treatment with Ad-OTUD7B showed decreased expression of α-SMA and collag[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Compared with the SCR group, CFs transfected with si-OTUD7B showed stronger migration ability, while in the Ad-OTUD7B group, the migration ability of CFs was weakened ( Fig. 5 A–B)."

sparser
"To manipulate OTUD7B expression, we employed small interfering RNA (si-OTUD7B) to suppress OTUD7B expression and adenoviral vectors carrying OTUD7B-overexpressing plasmids (Ad-OTUD7B) to enhance its expression."

sparser
"The CCK-8 assay revealed that si-OTUD7B treatment could promote the proliferation of fibroblasts, while Ad-OTUD7B could inhibit their proliferation ( Fig. 5 C)."
Sal-miR-1 affects OTUD7B
| 7 8
Sal-miR-1 inhibits OTUD7B.
| 7 3
Sal-miR-1 inhibits OTUD7B. 10 / 10
| 7 3

reach
"Mechanistically, Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via binding to the different sites of the OTUD7B 3 ' UTR."

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

eidos
"Mechanistically , Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via binding to the different sites of the OTUD7B 3'UTR ."

eidos
"OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels To clarify which substrate is regulated and deubiquitinated by OTUD7B in the context of VSMC migration and adhesion , we used 3 protein-protein interaction prediction databases ( Cytoscape : http://apps.cytoscape.org/apps/agilentliteraturesearch; inBio-Map : https://www.intomics.com/inbio/map.html#search; Genemania : http://genemania.org ) to search for putative proteins interacting with OTUD7B ."

eidos
"Importantly , OTUD7B downregulation by Sal-miR-1 and 3 results in a reduction in KLF4 protein level , which in turn relieves KLF4 repression of the expression of SM alpha-actin , SM22alpha , and SMMHC , thus facilitating VSMC contractile gene ( VSMC differentiation gene ) expression ."

reach
"Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via targeting the OTUD7B 3 ' UTR."

eidos
"We show here that OTUB7B upregulates the level of KLF4 protein , a stem cell pluripotency protein 41 , through interacting with and deubiquitylating KLF4 , a repressor of VSMC differentiation , whereas OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein level ."

eidos
"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 ."

eidos
"Results of luciferase reporter assays using OTUD7B 3'UTR or its mutant plasmids demonstrated that Sal-miR-1 and 3 could target the 3'UTR of OTUD7B mRNA and then inhibited OTUD7B expression ."

eidos
"Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via targeting the OTUD7B 3'UTR Because plant-derived miRNAs are known to be capable of regulating mammalian gene expression by binding to the 3 ' UTR of target genes 19 , 29 , we utilized the bioinformatic databases miRanda ( http://www.microrna.org/microrna/home.do ) , Targetscan ( http://www.targetscan.org/vert_72/ ) and RNAhybrid ( https://bibiserv.cebitec.uni-bielefeld.de/rnahybrid/ ) to predict Sal-miR-1 and 3 targets ( Figure S3A , Table S1 ) ."
Sal-miR-1 decreases the amount of OTUD7B.
| 3
Sal-miR-1 decreases the amount of OTUD7B. 3 / 3
| 3

reach
"Remarkably, Sal-miR-1 and 3 increased the expression levels of NMHC IIA by inhibiting OTUD7B expression and thus reducing KLF4 protein levels."

reach
"Sal-miR-1 and Sal-miR-1 obviously decreased the expression of OTUD7B and intimal hyperplasia induced by vascular injury, suggesting that OTUD7B plays the pro inflammatory and pro proliferation effects for VSMCs in response to vascular injury."

reach
"Next, we confirmed that Sal-miR-1 or Sal-miR-3 alone or together significantly inhibited the expression of OTUD7B mRNA and protein, but did not affect KLF3 and KLF10 expression, indicating the specificity of these two miRNA target recognition (XREF_SUPPLEMENTARY B-C)."
Sal-miR-1 activates OTUD7B.
| 2
Sal-miR-1 activates OTUD7B. 2 / 2
| 2

reach
"Considering that KLF4 is a transcription factor required for VSMC phenotype switching, and its stability is regulated by ubiquitination mediated protein degradation, it is reasoned that OTUD7B downregulation induced by Sal-miR-1 and 3 resulted in a decrease in KLF4 protein levels."

reach
"Results of luciferase reporter assays using OTUD7B 3 ' UTR or its mutant plasmids demonstrated that Sal-miR-1 and 3 could target the 3 ' UTR of OTUD7B mRNA and then inhibited OTUD7B expression."
OTUD7B affects RIPK1
1 2 1 | 9 1
OTUD7B deubiquitinates RIPK1.
1 1 1 | 3
OTUD7B deubiquitinates RIPK1. 5 / 5
1 1 | 3

"USP21 and Cezanne or <span class="match term0">OTUD7B</span> negatively regulate NFkappaB signaling by deubiquitinating and inactivating <span class="match term1">RIP1</span> upon TNF-alpha stimulation, providing a feedback loop in the proinflammatory signaling"

reach
"OTUD7B, a newly identified member of the A20 family of DUBs, inhibits RIP1 ubiquitination and downstream IKK activity and NF-kappaB signalling [XREF_BIBR]."

reach
"Also, the A20 family member Cezanne reportedly deubiquitylates RIP1 but seems to function non-redundantly to A20 [81] ."

reach
"Similar to A20, Cezanne is recruited to the TNF-RI complex upon TNF stimulation and promotes RIP1 de-ubiquitination, thereby decreasing NF-κB signaling [106] ."

"NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination."
OTUD7B deubiquitinates RIPK1 on K377. 1 / 1
1 |

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OTUD7B inhibits RIPK1.
1 | 3
OTUD7B inhibits RIPK1. 4 / 5
1 | 3

reach
"In addition, Cezanne blocked NF-κB pathway by targeting RIP1 for deubiquitination in epithelial and endothelial cells [ 20 ]."

reach
"However, combined pharmacological inhibition of RIPK1 activity (Nec1s) and apoptosis (zVAD-FMK) completely rescued survival of OTUD7b-deficient BMDC in vitro and in vivo indicating that OTUD7b inhibits RIPK1-independent and to a lesser extent RIPK1-dependent DC apoptosis [43]."

"NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination."

reach
"It indicated that SFN modulated the expression of Cezanne to induce K63-mediated sequential deubiquitination and K48-mediated proteasomal degradation of TRAF6 and RIP1, eventually inhibiting the NF-κB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B ubiquitinates RIPK1.
| 1
OTUD7B ubiquitinates RIPK1. 1 / 1
| 1

reach
"Further studies revealed that the modulation of TRAF6 and RIP1 ubiquitination by Cezanne played a key role in the mechanism of SFN inhibiting NF-κB pathway."
OTUD7B decreases the amount of RIPK1.
| 1
OTUD7B decreases the amount of RIPK1. 1 / 1
| 1

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"USP21 and Cezanne inhibit TNF-κB activation by regulating ubiquitin level of RIPK1 (D'Arcy et al., 2015)."
OTUD7B binds RIPK1.
| 1
| 1

sparser
"TNF stimulation also resulted in an interaction between TRAF2-RIPK1 and RIPK1-OTUD7b (Fig. xref )."
OTUD7B activates RIPK1.
| 1
OTUD7B activates RIPK1. 1 / 1
| 1

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"Cezanne functions at the level of the IκB kinase complex or upstream of TNF receptor (TNFR) signaling and prevents the degradation of RIP1 signal adapter protein [189]."
OTUD7B affects EGFR
1 1 | 10 2
OTUD7B deubiquitinates EGFR.
1 | 6
OTUD7B deubiquitinates EGFR. 7 / 7
1 | 6

reach
"OTUD7B deubiquitinated EGFR and facilitates downstream pathway MAPK."

reach
"LINC00976 targets OTUD7B, which deubiquitinates EGFR, thereby activating the MAPK signal [47]."

reach
"Therefore, we hypothesized that OTUD7B may deubiquitinate EGFR and activate downstream pathway MAPK."

reach
"Therefore, we found that Linc00976 promoted proliferation and invasion via MAPK pathway, which is activated by OTUD7B mediated EGFR deubiquitination and stability.However, the mechanism of linc00976 regulating OTUD7B expression was still not clear."

"USP21 and Cezanne or <span class="match term0">OTUD7B</span> negatively regulate NFkappaB signaling by deubiquitinating and inactivating RIP1 upon TNF-alpha stimulation, providing a feedback loop in the proinflammatory signaling"

reach
"Ultimately, OTUD7B mediates EGFR deubiquitination and stability and MAPK signaling pathway activation, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a feasible therapeutic target for PC."

reach
"Pareja et al. found that Cezanne promoted oncogenic signaling by deubiquitinating epidermal growth factor receptor (EGFR) to reduce its degradation in breast cancer( Pareja et al., 2012 )."
OTUD7B binds EGFR.
1 | 1 2
1 | 1 2

sparser
"Subsequently, the interaction between OTUD7B and EGFR was confirmed by co-immunoprecipitation and immunofluorescent staining (Fig. xref b, c)."

No evidence text available

reach
"Subsequently, the interaction between OTUD7B and EGFR was confirmed by co-immunoprecipitation and immunofluorescent staining (Fig. 6b, c)."

sparser
"The results presented in xref confirmed that Cezanne-1 overexpression associates with remarkably reduced ubiquitination of EGFR, as well as with stabilization the receptor and an increase in auto-phosphorylation."
OTUD7B activates EGFR.
| 3
OTUD7B activates EGFR. 3 / 4
| 3

reach
"Based on these results, Cezanne also accelerates EGFR recycling which may explain the mechanism mediating Cezanne expression and Osimertinib resistance."

reach
"These results suggested that Cezanne could promote autophagy activation and accelerate the recycling of EGFR, which facilitated Osimertinib resistance."

reach
"Consistently, compared with the focused distribution of EGFR after a 5 min stimulation, Cezanne OE would induce a more scattered distribution of EGFR after a 15 min stimulation of EGF, indicating that Cezanne could accelerate EGFR recycling (Fig. 7)."
KLF4 affects OTUD7B
| 8 7
KLF4 binds OTUD7B.
| 4 7
| 4 7

reach
"An immunoprecipitation-mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Kruppel-like factor 4)."

sparser
"Therefore, the interaction between OTUD7B and KLF4 was investigated further."

reach
"Therefore, the interaction between OTUD7B and KLF4 was investigated further."

sparser
"Series of OTUD7B and KLF4 fragments were constructed to further investigate the binding domains required for interaction between OTUD7B and KLF4."

sparser
"A region of OTUD7B (amino acid [aa] 151–aa446) and a region of KLF4 (aa200–aa397) were required for OTUD7B to bind to KLF4 (Figure  xref )."

reach
"Series of OTUD7B and KLF4 fragments were constructed to further investigate the binding domains required for interaction between OTUD7B and KLF4."

sparser
"In the further study, we utilized co-immunoprecipitation experiments to examine the interaction of OTUD7B with KLF4 and found that KLF4 was co-immunoprecipitated by anti-OTUD7B antibody."

sparser
"The specificity of their interaction was verified by increased association of OTUD7B with KLF4 in OTUD7B-overexpressed cells (Figure xref G)."

reach
"As anticipated, co-immunoprecipitation experiments revealed that OTUD7B interacted with and deubiquitylated KLF4."

sparser
"An immunoprecipitation–mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel‐like factor 4)."
KLF4 activates OTUD7B.
| 3
KLF4 activates OTUD7B. 3 / 3
| 3

reach
"These findings suggest that KLF4 mediates the regulatory effects of OTUD7B on phenylephrine‐stimulated CH."

reach
"34 These findings demonstrate that KLF4 mediates the effects of OTUD7B on CH regulation in response to phenylephrine stimulation, which is consistent with our study."

reach
"Phenylephrine‐induced CH potentiated by OTUD7B knockdown was completely blocked by the upregulation of KLF4 activity."
KLF4 inhibits OTUD7B.
| 1
KLF4 inhibits OTUD7B. 1 / 1
| 1

reach
"WB, immunofluorescence staining, and reverse transcription‐polymerase chain reaction demonstrated that the overexpression of KLF4 eliminated the role of the OTUD7B‐involved AKT pathway in regulating CH (Figure 7A through 7C)."
KDM1A affects OTUD7B
1 | 5 9
1 | 5 9

sparser
"These data highlight a dose‐limiting transcriptional regulation of genes involved in cell proliferation by OTUD7BLSD1 axis, which might explain why this pathway confers a proliferative advantage in a context‐dependent manner."

sparser
"Using recombinant proteins, we concluded that OTUD7B can directly interact with LSD1 in vitro (Figure xref , Supporting Information)."

sparser
"Taken all together, these results suggest that OTUD7B binds and stabilizes LSD1 via abrogating its ubiquitination‐dependent proteasomal degradation."

sparser
"Therefore, perturbation of OTUD7BLSD1 axis results in changes in both activating and repressive chromatin modification marks, providing a plausible mechanism for altered gene transcription due to OTUD7B loss."

sparser
"We next explored the clinical implications of OTUD7BLSD1 signaling."

No evidence text available

sparser
"Using OLco‐regulated gene sets revealed that loss of OTUD7B or LSD1 resulted in a significantly reduced expression of metastatic genes (Figure xref , Supporting Information), providing potential mechanistic clues explaining suppressed metastatic ability due to impaired OTUD7BLSD1 signaling."

reach
"2.1 OTUD7B Binds LSD1 and Regulates Its Stability."

sparser
"OTUD7B Binds LSD1 and Regulates Its Stability."

reach
"In addition to USP22 and USP28, ectopic OTUD7B also bound robustly to endogenous LSD1 (Figure  1A )."
TRAF3 affects OTUD7B
2 | 7 5
2 | 7 5

reach
"Non-canonical NF-κB activators induce the interaction of OTUD7B and TRAF3, thereby down-regulating TRAF3 ubiquitination and degradation and preventing aberrant non-canonical NF-κB activation."

sparser
"Mechanistically, OTUD7b binds to TRAF3 and deubiquitinates it in a signal-dependent manner."

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

sparser
"Non-canonical NF-κB activators induce the interaction of OTUD7B and TRAF3, thereby down-regulating TRAF3 ubiquitination and degradation and preventing aberrant non-canonical NF-κB activation."

No evidence text available

reach
"We found that Traf3 physically interacted with Otud7b in T cells (unpublished data), although we could not detect appreciable degradation of Traf3 along with TCR-CD28 ligation in either WT or Otud7b deficient T cells."

reach
"OTUD7B functions as an inhibitor of the noncanonical NF-κB pathway by deubiquitinating TNF receptor-associated Factor 3 (TRAF3) [8]."

No evidence text available

reach
"Activation of BAFFR increases OTUD7B expression and the newly synthesized deubiquitinase then binds to TRAF3 resulting in the formation of a high molecular weight complex including OTUDB7, TRAF3, TRAF2, and cIAP1/2."

reach
"Mechanistically, OTUD7b binds to TRAF3 and deubiquitinates it in a signal-dependent manner."
OTUD7B affects MAP3K14
2 | 3 2 7
OTUD7B inhibits MAP3K14.
| 3 6
| 3 6

sparser
"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."

sparser
"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."

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

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

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

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

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

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

eidos
"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 binds MAP3K14.
2 | 1
2 | 1

No evidence text available

sparser
"OTUD7B did not bind to NIK directly, but it did bind to TRAF3 (Fig.  xref a, b)."

No evidence text available
OTUD7B deubiquitinates MAP3K14.
| 1
OTUD7B deubiquitinates MAP3K14. 1 / 1
| 1

reach
"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 activates MAP3K14.
| 1
| 1

reach
"TRAF3 and TRAF2 could recruit cIAP1/2 to catalyze K48‐linked ubiquitination and subsequent degradation of NIK.11, 12 NLRP12 or OTUD7B stabilizes TRAF3 and subsequently accelerates NIK degradation.13, 14 Lastly, IKKα and TBK1 may induce NIK phosphorylation‐dependent degradation.15, 16 In contrast to NIK, little is known about how the downstream subunit p100/p52 is regulated."
OTUD7B affects TRAF6
1 2 1 | 5 3
OTUD7B binds TRAF6.
1 2 | 1 1
1 2 | 1 1

No evidence text available

sparser
"One of them is OTUD7B (also known as Cezanne), which interacts with TRAF6 and inhibits NF-κB activation upon overexpression [27,28] ."

No evidence text available

reach
"ZA20D1 can associate with Traf6 and is possibly an antagonist to Traf6."

No evidence text available
OTUD7B ubiquitinates TRAF6.
| 1 2
OTUD7B ubiquitinates TRAF6. 3 / 3
| 1 2

reach
"Further studies revealed that the modulation of TRAF6 and RIP1 ubiquitination by Cezanne played a key role in the mechanism of SFN inhibiting NF-κB pathway."

sparser
"Zengchuan Wang et al. observed that the regulation of TRAF6 and receptor-interacting protein (RIP1) ubiquitination by Cezanne played a key role in the mechanism by which Sulforaphane (SPN) inhibited t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In addition, SFN inhibits neuroinflammation through modulation of the ubiquitination of TNF receptor-associated factor 6 (TRAF6) and receptor-interacting protein 6 (RIP6) by Cezanne, a deubiquitinatin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B deubiquitinates TRAF6.
1 | 2
OTUD7B leads to the deubiquitination of TRAF6. 3 / 3
1 | 2

"<span class="match term0">Cezanne</span> regulates inflammatory responses to hypoxia in endothelial cells by targeting <span class="match term1">TRAF6</span> for deubiquitination"

reach
"These data indicate that endogenous Cezanne suppresses TRAF6 polyubiquitination in response to hypoxia-reoxygenation."

reach
"Cezanne modulates inflammatory responses to ischemia in endotheliocyte through inducing TRAF6 deubiquitination [ 41 ]."
OTUD7B inhibits TRAF6.
| 1
OTUD7B inhibits TRAF6. 1 / 1
| 1

reach
"It indicated that SFN modulated the expression of Cezanne to induce K63-mediated sequential deubiquitination and K48-mediated proteasomal degradation of TRAF6 and RIP1, eventually inhibiting the NF-κB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B affects FOXM1
1 | 8 4
OTUD7B binds FOXM1.
1 | 3 4
1 | 3 4

sparser
"In the present study, co-immunoprecipitation (co-IP) assay was used to investigate whether OTUD7B interacts with forkhead box protein M1 (FOXM1) and reduces FOXM1 ubiquitination to stabilize the FOXM1 protein."

sparser
"Whether FOXM1 is involved in the effects of OTUD7B on the stemness of breast cancer cells was explored in the present study, as was whether OTUD7B interacts with FOXM1 in breast cancer cells."

No evidence text available

sparser
"Co-immunoprecipitation assays demonstrated that OTUD7B interacted with forkhead box protein M1 (FOXM1) and reduced the polyubiquitylation of FOXM1 in breast cancer cells; accordingly, FOXM1 protein levels were significantly decreased by OTUD7B knockdown."

reach
"OTUD7B interacts with and stabilizes FOXM1 via deubiquitination."

reach
"HA-OTUD7B and Flag-FOXM1 plasmids were co-transfected into breast cancer cells and the interaction between OTUD7B and FOXM1 was detected by co-IP experiments."

sparser
"HA-OTUD7B and Flag-FOXM1 plasmids were co-transfected into breast cancer cells and the interaction between OTUD7B and FOXM1 was detected by co-IP experiments."

reach
"In the present study, it was revealed that OTUD7B interacts with and deubiquitinates FOXM1 in breast cancer cells, leading to the stabilization of FOXM1."
OTUD7B deubiquitinates FOXM1.
| 3
OTUD7B deubiquitinates FOXM1. 3 / 3
| 3

reach
"In the present study, co-immunoprecipitation (co-IP) assay was used to investigate whether OTUD7B interacts with forkhead box protein M1 (FOXM1) and reduces FOXM1 ubiquitination to stabilize the FOXM1 protein."

reach
"In the present study, it was revealed that OTUD7B interacts with and deubiquitinates FOXM1 in breast cancer cells, leading to the stabilization of FOXM1."

reach
"Co-immunoprecipitation assays demonstrated that OTUD7B interacted with forkhead box protein M1 (FOXM1) and reduced the polyubiquitylation of FOXM1 in breast cancer cells; accordingly, FOXM1 protein levels were significantly decreased by OTUD7B knockdown."
OTUD7B inhibits FOXM1.
| 1
OTUD7B inhibits FOXM1. 1 / 1
| 1

reach
"Furthermore, the present study investigated whether OTUD7B inhibits the proliferation and stemness of breast cancer cells by regulating the protein stability of FOXM1."
OTUD7B decreases the amount of FOXM1.
| 1
OTUD7B decreases the amount of FOXM1. 1 / 1
| 1

reach
"As shown in Fig. 3B, in the immunoprecipitate pulled down by the Flag antibody, the His-Ub level in the group with overexpression of HA-OTUD7B was markedly lower than that in the group without overexpression of HA-OTUD7B, indicating that OTUD7B reduced the ubiquitination level of Flag-FOXM1."
OTUD7B affects AKT
| 11 1
OTUD7B activates AKT.
| 6 1
OTUD7B activates AKT. 7 / 8
| 6 1

sparser
"Bin Wang et al. reported that genetic deletion of Cezanne in mice suppressed AKT activation in vivo , suggesting that Cezanne might activate AKT to protect cell survival( Wang et al., 2017 )."

reach
"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."

reach
"We found that Cezanne overexpression in NRCMs activated AKT/mTOR to reduce apoptosis, autophagy and oxidative stress; this mechanism of Cezanne was also verified in animal experiments."

reach
"To identify the underlying mechanism, we speculated that OTUD7B knockdown inhibits autophagy via the AKT/mTOR signaling pathway in PCa cells."

reach
"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)."

reach
"Bin Wang et al. reported that genetic deletion of Cezanne in mice suppressed AKT activation in vivo , suggesting that Cezanne might activate AKT to protect cell survival( Wang et al., 2017 )."

reach
"Overall, our results suggest that OTUD7B knockdown reduces autophagy by activating AKT/mTOR signaling in PC3 cells."
OTUD7B inhibits AKT.
| 2
OTUD7B inhibits AKT. 2 / 2
| 2

reach
"Taken together, OTUD7B promotes the proliferation, and autophagy, and inhibits apoptosis of prostate cancer cells via the AKT/mTOR signaling pathway."

reach
"Our observations indicated that OTUD7B deficiency significantly activated the PI3K‐AKT pathway by sequencing RNA extracted from the cardiac tissues of OTDU7B KO mice after TAC surgery."
OTUD7B increases the amount of AKT.
| 1
OTUD7B increases the amount of phosphorylated AKT. 1 / 1
| 1

reach
"As shown in Fig. 9 A, the levels of p-PI3K, p-AKT, and p-mTOR were restored by Cezanne overexpression after DOX treatment, consistent with the cellular experiments."
OTUD7B dephosphorylates AKT.
| 1
OTUD7B leads to the dephosphorylation of AKT. 1 / 1
| 1

reach
"Otud7b deficiency inhibited TCR-CD28-stimulated phosphorylation of Zap70, Akt, and Erks in both naive CD4 + T cells (XREF_FIG) and naive CD8 + T cells (XREF_FIG)."
OTUD7B decreases the amount of AKT.
| 1
OTUD7B decreases the amount of phosphorylated AKT. 1 / 1
| 1

reach
"OTUD7B knockdown significant increased the level of p-Akt and p-mTOR (Fig. 3B)."
ESR1 affects OTUD7B
1 3 | 2 7
ESR1 binds OTUD7B.
3 | 2 7
3 | 2 6

sparser
"OTUD7B interacts with ERα."

sparser
"GST pull-down assay showed that OTUD7B directly interacted with ERα in vitro (Fig. xref )."

sparser
"The interaction between OTUD7B and ERα suggested that ERα might be a substrate of OTUD7B, and therefore we evaluated the possibility of ERα deubiquitylation by OTUD7B. It was found that OTUD7B deletion dramatically decreased ERα protein level, and this effect could be reversed by addition of the proteasome inhibitor MG132 or overexpression of OTUD7B-WT, but not its catalytically inactive mutant OTUD7B C194S (Fig. xref )."

reach
"OTUD7B could interact with, deubiquitylate, and stabilize ERalpha in a deubiquitylation activity dependent manner."

reach
"Targeting the OTUD7B and ERalpha complex may prove to be a potential approach to treat patients with ERalpha positive breast cancer."

No evidence text available

No evidence text available

No evidence text available

sparser
"Targeting the OTUD7BERα complex may prove to be a potential approach to treat patients with ERα-positive breast cancer."

sparser
"OTUD7B was associated with ERα and inhibits ERα polyubiquitination and degradation."
| 1

sparser
"Additionally, deletion analysis demonstrated that OTUD7B physically interacted with the AF1 domain of ERα (Fig. xref )."
ESR1 decreases the amount of OTUD7B.
1 |
ESR1 decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
PARK7 affects OTUD7B
3 | 1 6
PARK7 binds OTUD7B.
3 | 1 5
3 | 1 5

No evidence text available

No evidence text available

No evidence text available

sparser
"DJ-1 also directly interacts with Cezanne, which networks with NF-κβ reducing its nuclear translocation working as a physiological inhibitor of its transcriptional activity [ xref ]."

sparser
"DJ-1 directly interacts with one of its binding partners, Cezanne, which is a physiological inhibitor of the transcription activity of NF-κβ [ xref ]."

sparser
"Another recent study [71] demonstrates the ability of DJ-1 to positively regulate NF-kB, thanks to the upstream DJ-1 binding to the deubiquitinating enzyme Cezanne that loses the inhibitory effect exe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The interaction of DJ-1 with Cezanne was shown by mass spectrometry and co-immunoprecipitation."

trips
"DJ-1 activates the noncanonical NF-kappaB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells."

sparser
"Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction."
PARK7 inhibits OTUD7B.
| 1
PARK7 inhibits OTUD7B. 1 / 1
| 1

sparser
"Activated DJ-1 inhibits Cezanne, leading to the increased ubiquitination and proteasomal degradation of RIP-1 and TRAF6 to turn off this suppression [ xref ], freeing NF-κB to transcribe the iNOS/NOS2 gene [ xref ]."
OTUD7B affects PIK3C3
4 | 6 2
OTUD7B binds PIK3C3.
4 | 1 1
4 | 1 1

sparser
"CO-IP assay showed that Cezanne could bind PIK3C3 rather than Beclin-1 (Fig. xref )."

reach
"CO-IP assay showed that Cezanne could bind PIK3C3 rather than Beclin-1 (Fig. 3B, C)."

No evidence text available

No evidence text available

No evidence text available

No evidence text available
OTUD7B increases the amount of PIK3C3.
| 3
OTUD7B increases the amount of PIK3C3. 3 / 3
| 3

reach
"In addition, OTUD7B knockdown significantly decreased levels of the autophagosome formation markers VPS34, ATG14L, and ATG7 and significantly increased p62."

reach
"As shown in Fig. 3A, our results showed that OTUD7B knockdown significantly decreased the levels of VPS34, ATG14L, p-Becline1, ATG7, and LC3B-II/I, while levels of P62 were significantly increased compared with the negative control cell."

reach
"Besides, we noticed that, in PC9 cells, Cezanne knockdown decreased PIK3C3 expression with or without the effect of CHX at protein level (Fig. 3D) but not mRNA levels (Supplementary Fig. 1C), and the addition of MG132 could recuse it (Fig. 3D)."
OTUD7B deubiquitinates PIK3C3.
| 2
OTUD7B leads to the deubiquitination of PIK3C3. 2 / 2
| 2

reach
"Besides, the enzymatic activity mutant Cezanne (C194S and H358R, Cezanne CH) could not decrease PIK3C3 ubiquitination (Fig. 4B), further confirming the deubiquitination effect of Cezanne on PIK3C3.To explore the motif or molecule basis of Cezanne and PIK3C3, we constructed plasmids composed of different part of these two proteins shown in Fig. 4C and Supplementary Fig. 1E."

reach
"CO-IP assays showed that Cezanne OE decreased PIK3C3 ubiquitination and induced a significant decrease of the K48-linked ubiquitination and a slight decrease of K11-linked ubiquitination of PIK3C3 (Fig. 4A), which were reported to mediate the degradation of target molecules [20]."
OTUD7B inhibits PIK3C3.
| 1
| 1

sparser
"Furthermore, immunoblot analysis of lysates from Hek 293 T cells transfected with K48-Ub, Myc-tagged PIK3C3 fragments showed the ubiquitination of V2 fragment of PIK3C3 was inhibited by Cezanne which indicated that the actual K48-linked ubiquitination lysine residue of PIK3C3 might locate at this fragment (Fig. xref )."
OTUD7B affects ESR1
3 | 2 7
3 | 2 6

sparser
"OTUD7B interacts with ERα."

sparser
"GST pull-down assay showed that OTUD7B directly interacted with ERα in vitro (Fig. xref )."

sparser
"The interaction between OTUD7B and ERα suggested that ERα might be a substrate of OTUD7B, and therefore we evaluated the possibility of ERα deubiquitylation by OTUD7B. It was found that OTUD7B deletion dramatically decreased ERα protein level, and this effect could be reversed by addition of the proteasome inhibitor MG132 or overexpression of OTUD7B-WT, but not its catalytically inactive mutant OTUD7B C194S (Fig. xref )."

reach
"OTUD7B could interact with, deubiquitylate, and stabilize ERalpha in a deubiquitylation activity dependent manner."

reach
"Targeting the OTUD7B and ERalpha complex may prove to be a potential approach to treat patients with ERalpha positive breast cancer."

No evidence text available

No evidence text available

No evidence text available

sparser
"Targeting the OTUD7BERα complex may prove to be a potential approach to treat patients with ERα-positive breast cancer."

sparser
"OTUD7B was associated with ERα and inhibits ERα polyubiquitination and degradation."
| 1

sparser
"Additionally, deletion analysis demonstrated that OTUD7B physically interacted with the AF1 domain of ERα (Fig. xref )."
LEF1 affects OTUD7B
2 | 4 6
2 | 3 6

sparser
"OTUD7B and LEF1 interact with each other through the UBA and HMG domains, respectively."

sparser
"LEF1 Interacts with OTUD7B through the HMG and UBA Domains, Respectively."

sparser
"The interaction between LEF1 and OTUD7B occurs through the HMG and UBA domains of LEF1 and OTUD7B, respectively."

sparser
"To determine which domains are responsible for the interaction between LEF1 and OTUD7B, we generated three deletion mutants of LEF1: LEF1ΔHMG (High Mobility Group domain deleted, aa 1-804), LEF1ΔCRD (context-dependent regulatory domain deleted, aa 1-201 & 805-1116), and LEF1ΔBCBD (β-catenin binding domain deleted, aa 202-1116) ( xref A) using the MYC-LEF1 plasmid."

No evidence text available

No evidence text available

reach
"To determine which domains are responsible for the interaction between LEF1 and OTUD7B, we generated three deletion mutants of LEF1: LEF1ΔHMG (High Mobility Group domain deleted, aa 1-804), LEF1ΔCRD (context-dependent regulatory domain deleted, aa 1-201 & 805-1116), and LEF1ΔBCBD (β-catenin binding domain deleted, aa 202-1116) (Figure 2A) using the MYC-LEF1 plasmid."

reach
"This result suggests that LEF1 binds to OTUD7B through its N-terminus, which contains the UBA domain."

sparser
"As shown in xref D, the full-length OTUD7B and all three mutant forms interacted with LEF1."

sparser
"This result suggests that LEF1 binds to OTUD7B through its N-terminus, which contains the UBA domain."
OTUD7B binds LEF1 and HMG domain. 1 / 1
| 1

reach
"This result demonstrates that OTUD7B binds to LEF1 through its HMG domain."
ZAP70 affects OTUD7B
| 4 7
| 4 7

sparser
"This ubiquitination-defective Zap70 mutant was also attenuated in association with Otud7b, consistent with the idea that the Zap70Otud7b interaction might be facilitated by Zap70 ubiquitination ( xref )."

reach
"In response to TCR-CD28 ligation, Otud7b rapidly bound to Zap70 and inhibited Zap70 ubiquitination."

reach
"Otud7b binds to and deubiquitinates Zap70."

reach
"The Otud7b-Zap70 interaction was further confirmed using a transient transfection experiment in which the overexpressed Otud7b strongly associated with Zap70 (XREF_FIG)."

sparser
"In response to TCR signaling, Otud7b was rapidly recruited to Zap70 via a mechanism that required the UBA domain of Otud7b, suggesting the possibility that Otud7b interacted with ubiquitinated Zap70."

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

sparser
"In response to TCR–CD28 ligation, Otud7b rapidly bound to Zap70 and inhibited Zap70 ubiquitination."

sparser
"Interestingly, although Otud7b did not bind Zap70 in resting T cells, these two proteins formed a complex upon TCR–CD28 stimulation ( xref )."

sparser
"The Otud7bZap70 interaction was further confirmed using a transient transfection experiment in which the overexpressed Otud7b strongly associated with Zap70 ( xref )."

sparser
"Domain mapping analyses revealed the requirement of the N-terminal UBA domain of Otud7b for its physical interaction with Zap70 ( xref ), indicating the facilitation of Otud7bZap70 interaction by ubiquitination."
OTUD7B affects PARK7
3 | 1 5
3 | 1 5

No evidence text available

No evidence text available

No evidence text available

sparser
"DJ-1 also directly interacts with Cezanne, which networks with NF-κβ reducing its nuclear translocation working as a physiological inhibitor of its transcriptional activity [ xref ]."

sparser
"DJ-1 directly interacts with one of its binding partners, Cezanne, which is a physiological inhibitor of the transcription activity of NF-κβ [ xref ]."

sparser
"Another recent study [71] demonstrates the ability of DJ-1 to positively regulate NF-kB, thanks to the upstream DJ-1 binding to the deubiquitinating enzyme Cezanne that loses the inhibitory effect exe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The interaction of DJ-1 with Cezanne was shown by mass spectrometry and co-immunoprecipitation."

trips
"DJ-1 activates the noncanonical NF-kappaB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells."

sparser
"Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction."
| 1 10
| 7

reach
"Strikingly, the OTUD7B defect promoted the association of LSD1 with p62 and targeted LSD1 for p62-mediated proteasomal degradation, thereby eliminating breast cancer metastasis."

reach
"In ERα-negative breast cancer, silencing OTUD7B markedly inhibits the migration and invasion of cancer cells in vitro, and significantly impairs lung metastasis in vivo (16)."

reach
"Knockdown of either OTUD7B or LSD1 significantly reduced the expression of metastasis-associated genes and effectively suppressed the metastasis of breast cancer cells."

reach
"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."

reach
"Mechanistically, OTUD7B likely promotes GC metastasis through the WNT signaling pathway, specifically targeting β-catenin."

reach
"OTUD7B serves as a novel marker for poor prognosis in GC and actively promotes tumor metastasis."

reach
"These results highlight a pivotal role of OTUD7B‐mediated deubiquitination of LSD1 in modulating its genomic occupancy and the regulation of gene transcription.2.7 OTUD7B Promotes Metastasis via LSD1."
| 1 3

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 ."

reach
"However, in hepatocellular carcinoma (HCC), OTUD7B may function as a tumor suppressor, which is evidenced by the fact that OTUD7B knockdown accelerates the migration and invasion of HCC cells in vitro and promotes metastasis in vivo."

reach
"Furthermore, RNA sequencing and bioinformatic analyses indicated that the absence of OTUD7B suppressed signaling pathways related to cancer progression, metastasis, and metabolism."

reach
"In ERα-negative breast cancer, silencing OTUD7B inhibits cell migration and invasion in vitro and impairs lung metastasis of cancer cells in vivo by increasing lysine-specific demethylase 1 (LSD1)-Ub and targeting LSD1 for p62-mediated proteolysis (16)."
| 6

reach
"In ERα-negative breast cancer, silencing OTUD7B markedly inhibits the migration and invasion of cancer cells in vitro, and significantly impairs lung metastasis in vivo (16)."

reach
"Chen et al. reported that OTUD7B promotes proliferation, migration, and invasion by stabilizing N1ICD in pancreatic cancer [20]."

reach
"In vitro assays revealed that genetic knockout of OTUD7B markedly reduced the migration and invasion of GC cells, while overexpression of OTUD7B led to enhanced cellular migration and invasion."

reach
"The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137."

reach
"OTUD7B promotes cell migration and invasion, predicting poor prognosis of gastric cancer."

reach
"In ERα-negative breast cancer, silencing OTUD7B inhibits cell migration and invasion in vitro and impairs lung metastasis of cancer cells in vivo by increasing lysine-specific demethylase 1 (LSD1)-Ub and targeting LSD1 for p62-mediated proteolysis (16)."
| 2 3

reach
"Depletion of ZA20D1 also reduced SCC invasion, which further suggests that it has additional functions besides antagonising Traf6 (XREF_SUPPLEMENTARY)."

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

reach
"However, in hepatocellular carcinoma (HCC), OTUD7B may function as a tumor suppressor, which is evidenced by the fact that OTUD7B knockdown accelerates the migration and invasion of HCC cells in vitro and promotes metastasis in vivo."

reach
"16 , 17 Molecularly, OTUD7B inhibits LCL161 inhibitor of apoptosis protein antagonist‐induced invasion and migration by binding to and deubiquitinating TRAF3 (tumor necrosis factor receptor‐associated factor 3), thereby inhibiting NIK (NF‐κB‐inducing kinase) and preventing noncanonical NF‐κB activation in lung cancer."

eidos
"* 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 ."
| 11
OTUD7B inhibits Hypertrophy.
| 6
| 6

reach
"Histological examinations using H&E (Fig. 2G), WGA (Fig. 2H), Masson (Fig. 2J, K), and Sirius Red staining (Fig. 2L, M) consistently indicated that OTUD7B knockdown significantly intensified pressure overload-induced cardiac hypertrophy and fibrosis."

reach
"Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery-induced myocardial hypertrophy, abnormal cardiac function, and fibrosis."

reach
"In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation-induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect."

reach
"Our animal experiments revealed that Cezanne overexpression in mice reversed DOX-induced cardiomyocyte apoptosis, autophagy, oxidative stress and hypertrophy."

reach
"Collectively, these findings demonstrate that OTUD7B knockdown exacerbates pressure overload-induced myocardial hypertrophy and fibrosis, leading to deteriorated cardiac function."

reach
"OTUD7B knockdown causes a reprogramming of fatty acid metabolism in pathological cardiac hypertrophy."
OTUD7B activates Hypertrophy.
| 5
| 5

reach
"Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site-linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway."

reach
"OTUD7B alleviates PE-induced cardiomyocyte hypertrophy in vitro."

reach
"These findings indicate that OTUD7B effectively mitigates PE-induced pathological myocardial hypertrophy (Fig. 3E, F, G, H)."

reach
"Cardiac-specific OTUD7B deficiency exacerbated, while OTUD7B overexpression mitigated, pressure overload-induced hypertrophy and cardiac dysfunction both in vivo and in vitro."

reach
"OTUD7B mitigates dysregulation of fatty acid metabolism in PE-induced cardiac hypertrophy."
OTUD7B is modified
9 | 2
OTUD7B is phosphorylated.
9 |
OTUD7B is phosphorylated on S100. 3 / 3
3 |

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No evidence text available
OTUD7B is phosphorylated on S464. 3 / 3
3 |

No evidence text available

No evidence text available

No evidence text available
OTUD7B is phosphorylated on S467. 2 / 2
2 |

No evidence text available

No evidence text available
OTUD7B is phosphorylated on S449. 1 / 1
1 |

No evidence text available
OTUD7B is hydroxylated.
| 2
OTUD7B is hydroxylated. 2 / 2
| 2

sparser
"For instance, hydroxylation of the UBA domain of OTUD7B (Cezanne) by factor inhibiting HIF1 (FIH1) prevents binding to Ub ( Mader et al., 2020 )."

sparser
"Cezanne is hydroxylated at Asn35 of the UBA domain in an oxygen- or FIH1-dependent manner, which inhibits the binding of Ub to Cezanne ( xref )."
TP53 affects OTUD7B
| 4 6
| 3 6

sparser
"Furthermore, given both HepG2 and SMMC-7721 cells are known to express wildtype (WT) p53, it was important to determine if p53 mutations which are prevalent in HCC affect OTUD7B-p53 interactions."

sparser
"Others have shown retinoic acid (RA) treatment increases OTUD7B levels in HCC xref while we observed that OTUD7B was subject to transcriptional repression by p53: the latter finding further suggests that p53 establishes negative feedback towards tuning the cellular levels of OTUD7B. It is further noteworthy to consider how the wiring of the OTUD7B-p53 relationship may dovetail with the well-known Mdm2-p53 regulatory circuit."

sparser
"Clinical data analysis showed a positive correlation between OTUD7B and p53 protein levels in HCC tissues, suggesting that the OTUD7B-p53 axis may represent a potential therapeutic target for HCC xref ."

reach
"Thus, OTUD7B physically associates with p53 through dual interfaces within the p53 TAD (1-60) and DBD (98-292) regions.Additional characterization using nuclear-cytoplasmic separation showed a biased distribution of OTUD7B within the cytoplasm of HCC cells while p53 occurred both in the cytoplasm and nucleus (Figure 1I)."

reach
"Furthermore, given the observation that OTUD7B binds mutant forms of p53, it was relevant to examine the capability of OTUD7B to deubiquitinate mutant p53."

sparser
"Moreover, interactions between the endogenous OTUD7B and p53 proteins were demonstrable in HepG2 cells (Figure xref F)."

sparser
"Further mapping experiments were then conducted using a range of p53 deletion constructs (Figure xref G) towards defining the regions of interaction between OTUD7B and p53."

sparser
"Thus, OTUD7B physically associates with p53 through dual interfaces within the p53 TAD (1-60) and DBD (98-292) regions."

reach
"Further mapping experiments were then conducted using a range of p53 deletion constructs (Figure 1G) towards defining the regions of interaction between OTUD7B and p53."
OTUD7B binds mutated TP53. 1 / 1
| 1

reach
"IP experiments in MHCC-97H (harboring R249S TP53) and Huh7 (harboring Y220C TP53) cells confirmed interactions between endogenous OTUD7B and mutant p53 (Figure 1K)."
OTUD7B affects TRAF2
| 5 5
OTUD7B binds TRAF2.
| 3 5
| 3 5

sparser
"Deletion of the UBA domain resulted in complete loss of interaction between OTUD7b and TRAF2."

sparser
"In addition, loss of the active catalytic site C194 showed reduction in binding of OTUD7b to TRAF2 upon TNF stimulation, presumably by disruption of the TRAF binding region spanning the catalytic domain of OTUD7b."

reach
"Immunoprecipitation experiments showed that the interaction between TRAF2 and OTUD7b was completely abolished by deletion of the N-terminal UBA domain."

reach
"Deletion of the UBA domain resulted in complete loss of interaction between OTUD7b and TRAF2."

sparser
"Our co-immunoprecipitation experiments showed induced interaction of OTUD7b with TRAF2 upon TNF stimulation (Fig. xref ), Since proteasomal degradation of the substrate is mediated either by K11- or K48-linked polyubiquitin chains, we next determined K48- and K11-linked polyubiquitin chains on TRAF2."

reach
"In addition, loss of the active catalytic site C194 showed reduction in binding of OTUD7b to TRAF2 upon TNF stimulation, presumably by disruption of the TRAF binding region spanning the catalytic domain of OTUD7b.The in vivo function of OTUD7b in infectious diseases has been sparsely studied."

sparser
"Immunoprecipitation experiments showed that the interaction between TRAF2 and OTUD7b was completely abolished by deletion of the N-terminal UBA domain."

sparser
"In line with our data after long-term exposure to TNF (Fig. xref ), we observed (i) enhanced proteasomal degradation of TRAF2 (Fig. xref ), (ii) TNF-induced OTUD7b-TRAF2 interaction (Fig. xref ) (iii) increased levels of K48-linked polyubiquitin chains on TRAF2 (Fig. xref ), (iv) interaction of TRAF2 with RIPK1 and OTUD7b with RIPK1 (Fig. xref ), and consequently, (v) reduced K63-linked polyubiquitination of RIPK1 (Fig. xref )."
OTUD7B activates TRAF2.
| 2
OTUD7B activates TRAF2. 2 / 2
| 2

reach
"The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2."

reach
"DC-specific OTUD7b augments NF-kappaB and MAP kinase signaling by stabilizing TRAF2."
OTUD7B affects SOX2
3 1 | 3 3
OTUD7B binds SOX2.
3 | 3
3 | 1

No evidence text available

No evidence text available

No evidence text available

sparser
"Then we detected the interaction between Sox2 and OTUD7B at endogenous (Fig.  xref ) and exogenous (Supplementary Fig.  xref ) levels and mapped the Sox2-binding region of OTUD7B to the C-terminal zinc finger (ZF) domain (Fig.  xref )."
| 2

sparser
"To further confirm the direct binding of Sox2 to OTUD7B ZF domain, we purified recombinant GST-tagged OTUD7B truncates, including GST-OTUD7B-N (1-359), GST-OTUD7B-C (360–843), GST-OTUD7B-△ZF (1–810), and GST-OTUD7B-ZF (811–843) (Fig.  xref )."

sparser
"The result of GST pull-down assay indicated that Sox2 interacted with OTUD7B ZF domain directly in cell-free system (Fig.  xref )."
OTUD7B increases the amount of SOX2.
| 2
OTUD7B increases the amount of SOX2. 2 / 2
| 2

reach
"It was previously reported that Otud7b is a deubiquitinase that deubiquitinates and stabilizes Sox2 and promotes the maintenance of neural progenitor cells.61 Otud7b silencing decreases Sox2 levels and promotes neuronal differentiation in cultured cells."

reach
"The protein expression levels of SOX2 and Nanog, two stemness-associated proteins, were markedly suppressed by OTUD7B knockdown (Fig. 2A)."
OTUD7B deubiquitinates SOX2.
1 | 1
OTUD7B deubiquitinates SOX2. 2 / 2
1 | 1

reach
"It was previously reported that Otud7b is a deubiquitinase that deubiquitinates and stabilizes Sox2 and promotes the maintenance of neural progenitor cells.61 Otud7b silencing decreases Sox2 levels and promotes neuronal differentiation in cultured cells."

"COP1, as the substrate receptor, interacts directly with and ubiquitylates <span class="match term1">Sox2</span>, while <span class="match term0">OTUD7B</span> removes polyUb conjugates from <span class="match term1">Sox2</span> and increases its stability"
OTUD7B affects OTUD7A
2 | 1 7
2 | 1 7

sparser
"Interestingly, a recent study showed that OTUD7A and OTUD7B interact with and modify Lys11/Lys63 heterotypic chains in order to regulate DNA damage [ xref ]."

sparser
"Analogously, OTUD7A interacted with OTUD7B to promote OTUD7B recruitment of Rap80/BRCA1-A, Rad18, and 53bp1, which enhanced cellular resistance to ionizing radiation, and DNA damage repair ( xref )."

sparser
"In addition, Cezanne2 interacts with Cezanne ( xref D), and the DUB activity of Cezanne2 is important for its function ( xref B)."

sparser
"Thus, Cezanne and Cezanne2 likely form a complex, with both of the DUB activities required for promoting recruitment of DNA repair factors."

sparser
"Increased Lys11-linkage ubiquitination due to lack of Cezanne DUB activity compromises the recruitment of Rap80/BRCA1-A. Cezanne2 interacts with Cezanne, facilitating Cezanne in the recruitment of Rap80/BRCA1-A, Rad18, and 53BP1, in cellular resistance to ionizing radiation and DNA repair."

sparser
"Cezanne2 interacts with Cezanne, playing a facilitating role in Rap80/Abraxas/BRCA1, Rad18, and 53BP1 recruitment, DNA repair, and cellular resistance to IR."

No evidence text available

reach
"Thus, it is likely that Cezanne and Cezanne2 form a complex and that the DUB activity of both of these two proteins is required for promoting Rap80/Abraxas/BRCA1, Rad18, and 53BP1 recruitment.Due to the role of Cezanne and Cezanne2 in the recruitment of the Rap80/BRCA1-A complex, Rad18, and 53BP1, we examined their roles in DNA damage repair and cellular resistance to IR."

sparser
"Cezanne2 interacts with Cezanne, promoting recruitment of Rap80/Abraxas and 53BP1 and DNA repair."

No evidence text available
OTUD7B affects HNF4A
| 4 5
OTUD7B binds HNF4A.
| 1 5
| 1 5

sparser
"OTUD7B directly interacts with HNF4α and regulates the stability of HNF4α protein through deubiquitination."

sparser
"Molecular docking analysis indicated a potential interaction between OTUD7B and HNF4α, with a docking score of −258.68 and a confidence score of 0.8979 (Fig. xref A)."

reach
"Molecular docking analysis indicated a potential interaction between OTUD7B and HNF4α, with a docking score of −258.68 and a confidence score of 0.8979 (Fig. 7A)."

sparser
"We used TransDSI to assess whether HNF4α is a deubiquitination substrate of OTUD7B. The TransDSI score for the OTUD7B-HNF4α interaction was 0.7979, suggesting a high probability that HNF4α is a substrate of OTUD7B."

sparser
"Mechanistically, OTUD7B interacts with HNF4α and deubiquitinates it at the K48 site, thereby stabilizing its expression."

sparser
"CoIP further confirmed these findings, demonstrating that OTUD7B directly interacts with HNF4α (Fig. xref B)."
OTUD7B deubiquitinates HNF4A.
| 2
OTUD7B leads to the deubiquitination of HNF4A. 2 / 2
| 2

reach
"Our results demonstrated that OTUD7B markedly decreased the ubiquitination of HNF4α (Fig. 7F)."

reach
"Our findings revealed that OTUD7B significantly reduced HNF4α ubiquitination in cells expressing HA-Ub-K48 (Fig. 7G)."
OTUD7B activates HNF4A.
| 1
OTUD7B activates HNF4A. 1 / 1
| 1

reach
"Notably, in the presence of MG132, the protein level of HNF4α was not affected by OTUD7B, suggesting that OTUD7B inhibits HNF4α degradation via ubiquitin–proteasome system."
Hypoxia affects OTUD7B
| 3 6
Hypoxia activates OTUD7B.
| 2 5
| 2 5

reach
"Our finding that Cezanne can be induced by hypoxia in vitro led us to examine the expression of Cezanne in tissues exposed to ischemia in vivo."

reach
"Studies of cultured endothelial cells (EC) demonstrated that hypoxia (1% oxygen) induced Cezanne via p38 MAP kinase-dependent transcriptional and post- transcriptional mechanisms."

eidos
"Methods and Results Studies of cultured endothelial cells ( EC ) demonstrated that hypoxia ( 1 % oxygen ) induced Cezanne via p38 MAP kinase-dependent transcriptional and post - transcriptional mechanisms ."

reach
"Hypoxia induces Cezanne via transcriptional and post-transcriptional mechanisms."

reach
"This level of hypoxia (1% O2) also induced Cezanne in cultured microvascular EC at both the mRNA (Fig. 1C) and protein levels (Online Fig. II)."

reach
"Activation of HIF1α in response to dimethyloxallyl glycine, desferrioxamine or CoCl did not influence Cezanne expression (Online Fig. III) and silencing of HIF1α or HIF2α did not suppress Cezanne expression in hypoxic EC (Online Fig. IV), indicating that induction of Cezanne by hypoxia is HIF-independent."

eidos
"There is also evidence showing that hypoxia can induce OTUD7B via a p38 MAPK pathway [ 126 ] and UCHL1 expression involving a HIF-alpha-mediated mechanism [ 144 ] ."
Hypoxia inhibits OTUD7B.
| 1 1
| 1 1

reach
"We observed that silencing of ATF2 using two different siRNA sequences suppressed the induction of Cezanne by hypoxia (Fig. 2B)."

eidos
"We observed that silencing of ATF2 using two different siRNA sequences suppressed the induction of Cezanne by hypoxia ( Fig. 2B ) ."
FOXM1 affects OTUD7B
1 | 4 4
FOXM1 binds OTUD7B.
1 | 3 4
1 | 3 4

sparser
"In the present study, co-immunoprecipitation (co-IP) assay was used to investigate whether OTUD7B interacts with forkhead box protein M1 (FOXM1) and reduces FOXM1 ubiquitination to stabilize the FOXM1 protein."

sparser
"Whether FOXM1 is involved in the effects of OTUD7B on the stemness of breast cancer cells was explored in the present study, as was whether OTUD7B interacts with FOXM1 in breast cancer cells."

No evidence text available

sparser
"Co-immunoprecipitation assays demonstrated that OTUD7B interacted with forkhead box protein M1 (FOXM1) and reduced the polyubiquitylation of FOXM1 in breast cancer cells; accordingly, FOXM1 protein levels were significantly decreased by OTUD7B knockdown."

reach
"OTUD7B interacts with and stabilizes FOXM1 via deubiquitination."

reach
"HA-OTUD7B and Flag-FOXM1 plasmids were co-transfected into breast cancer cells and the interaction between OTUD7B and FOXM1 was detected by co-IP experiments."

sparser
"HA-OTUD7B and Flag-FOXM1 plasmids were co-transfected into breast cancer cells and the interaction between OTUD7B and FOXM1 was detected by co-IP experiments."

reach
"In the present study, it was revealed that OTUD7B interacts with and deubiquitinates FOXM1 in breast cancer cells, leading to the stabilization of FOXM1."
FOXM1 inhibits OTUD7B.
| 1
FOXM1 inhibits OTUD7B. 1 / 1
| 1

reach
"Furthermore, the overexpression of FOXM1 reduced the inhibitory effects of OTUD7B knockdown on breast cancer cells."
TRAF2 affects OTUD7B
| 3 5
| 3 5

sparser
"Deletion of the UBA domain resulted in complete loss of interaction between OTUD7b and TRAF2."

sparser
"In addition, loss of the active catalytic site C194 showed reduction in binding of OTUD7b to TRAF2 upon TNF stimulation, presumably by disruption of the TRAF binding region spanning the catalytic domain of OTUD7b."

reach
"Immunoprecipitation experiments showed that the interaction between TRAF2 and OTUD7b was completely abolished by deletion of the N-terminal UBA domain."

reach
"Deletion of the UBA domain resulted in complete loss of interaction between OTUD7b and TRAF2."

sparser
"Our co-immunoprecipitation experiments showed induced interaction of OTUD7b with TRAF2 upon TNF stimulation (Fig. xref ), Since proteasomal degradation of the substrate is mediated either by K11- or K48-linked polyubiquitin chains, we next determined K48- and K11-linked polyubiquitin chains on TRAF2."

reach
"In addition, loss of the active catalytic site C194 showed reduction in binding of OTUD7b to TRAF2 upon TNF stimulation, presumably by disruption of the TRAF binding region spanning the catalytic domain of OTUD7b.The in vivo function of OTUD7b in infectious diseases has been sparsely studied."

sparser
"Immunoprecipitation experiments showed that the interaction between TRAF2 and OTUD7b was completely abolished by deletion of the N-terminal UBA domain."

sparser
"In line with our data after long-term exposure to TNF (Fig. xref ), we observed (i) enhanced proteasomal degradation of TRAF2 (Fig. xref ), (ii) TNF-induced OTUD7b-TRAF2 interaction (Fig. xref ) (iii) increased levels of K48-linked polyubiquitin chains on TRAF2 (Fig. xref ), (iv) interaction of TRAF2 with RIPK1 and OTUD7b with RIPK1 (Fig. xref ), and consequently, (v) reduced K63-linked polyubiquitination of RIPK1 (Fig. xref )."

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

reach
"Cezanne reduces inflammation and injury in response to ischemia-reperfusion."

reach
"Based on this feature, researchers first focused on the role of Cezanne in suppressing inflammation."

reach
"We translated our in vitro findings to a murine model by demonstrating that renal inflammation and injury in response to ischemia/reperfusion is enhanced by genetic deletion of Cezanne."

reach
"Our observation that endogenous Cezanne can reduce inflammation and injury in response to ischemia-reperfusion has important implications for therapeutic targeting of inflammation during transplantation of vascularised organs, bypass grafting, percutaneous coronary intervention of arteries and other procedures that involve reperfusion."

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

reach
"The evidence suggests that there was a strong correlation between the release of CA125 and IFN-γ in psoriatic patients.Since A20, CYLD and Cezanne negatively regulate the inflammatory response in autoimmune and cancer diseases, their mRNA levels were examined by quantitative real-time PCR."

eidos
"In vascular endothelial cells , OTUD7B could reduce inflammation and injury in response to ischemia-reperfusion 45 ."
OTUD7B affects YAP1
3 | 3 1
OTUD7B binds YAP1.
3 | 1 1
3 | 1 1

No evidence text available

No evidence text available

No evidence text available

reach
"Co-immunoprecipitation (Co-IP) and ubiquitination assays showed the interaction of OTUD7B and YAP1."

sparser
"Co-immunoprecipitation (Co-IP) and ubiquitination assays showed the interaction of OTUD7B and YAP1."
OTUD7B activates YAP1.
| 2
OTUD7B activates YAP1. 2 / 2
| 2

reach
"OTUD7B accelerated gastric cancer progression by deubiquitizing and stabilizing YAP1 [21]."

reach
"Mechanically, OTUD7B promoted downstream target genes of YAP1 including NUAK2, Snail, Slug, CDK6, CTGF, and BIRC5."
OTUD7B affects Neoplasms
| 1 6
OTUD7B activates Neoplasms.
| 1 3
| 1 3

reach
"OTUD7B serves as a novel marker for poor prognosis in GC and actively promotes tumor metastasis."

eidos
"Recent studies suggested that OTUD7B may promote cancer progression by activating oncogenic pathways including EGFR and mTORC2 / Akt signaling [ 62,238 ] ."
| PMC

reach
"Additionally, OTUD7B promotes tumor growth through the AKT/VEGF signaling pathway in lung adenocarcinoma [26]."

reach
"21 Moreover, OTUD7B promotes tumor progression via the AKT/VEGF (vascular endothelial growth factor) pathway in lung squamous carcinoma and adenocarcinoma."
OTUD7B inhibits Neoplasms.
| 3
| 3

reach
"Inhibition of Cezanne enables tumor survival through increased expression of IL-8 and ICAM-1 [65]."

reach
"Conversely, OTUD7B knockdown promoted tumor growth."

reach
"These studies propose that OTUD7B suppresses tumor progression in HCC although the underlying molecular mechanisms and cause of OTUD7B downregulation in HCC are largely unknown.HCC is one of the most common malignant tumors, ranking sixth in incidence and second in mortality rate among cancers worldwide."
OTUD7B affects IRF3
2 | 1 1 3
OTUD7B binds IRF3.
2 | 3
2 | 3

sparser
"OTUD7B directly interacts with IRF3 and activates p62 by removing K63 polyubiquitin chains leading to enhanced p62 oligomerization."

sparser
"Mechanistically, OTUD7B interacts with IRF3, and activates IRF3-associated cargo receptor SQSTM1/p62 (sequestosome 1) by removing its K63-linked poly-ubiquitin chains at lysine 7 (K7) to enhance SQSTM1 oligomerization."

No evidence text available

No evidence text available

sparser
"RNF26 played a role in EGFR‐driven cell proliferation by ubiquitinating Sqstm1, [ xref ] while mutation of Sqstm1 at K420 led to abnormal ubiquitination and thus inhibited autophagy. [ xref ] TRIM21 could bind to the PB1 domain to ubiquitinate K7, hindering the oligomerization of Sqstm1 and inhibiting its function. [ xref ] CUL5‐ASB6 complex promoted the ubiquitination of Sqstm1 for degradation to inhibit cell proliferation and autophagy. [ xref ] In addition, RNF166 and NEDD4 activated autophagy through ubiquitination of Sqstm1. [ xref ] KEAP1‐CUL3 ubiquitinated Sqstm1 at the site of K420 within the UBA domain, improved the efficiency of substrate transport to the autophagosome, enhanced selective autophagic flux, and accelerated the degradation of target proteins. [ xref ] The ubiquitin‐specific peptidase USP8 acted as a negative regulator of autophagy by deubiquitinating Sqstm1 at K420. [ xref ] The deubiquitinating enzyme OTUD7B interacted with IRF3 to remove the polyubiquitin chain at the K7 site of Sqstm1 to enhance the oligomerization for the block of antiviral immune response. [ xref ] In this study, we found that RNF6, an E3 ubiquitin ligase, mediated the ubiquitination of Sqstm1 at K314 to promote autophagy."
OTUD7B inhibits IRF3.
| 1 1
OTUD7B inhibits IRF3. 2 / 2
| 1 1

reach
"OTUD7B serves as a deubiquitinase of P62/SQSTM1 and enhances the degradation of IRF-3 [51,52]."

eidos
"OTUD7B deubiquitinates SQSTM1 / p62 and promotes IRF3 degradation to regulate antiviral immunity ."
HNF4A affects OTUD7B
1 | 1 5
HNF4A binds OTUD7B.
| 1 5
| 1 5

sparser
"OTUD7B directly interacts with HNF4α and regulates the stability of HNF4α protein through deubiquitination."

sparser
"Molecular docking analysis indicated a potential interaction between OTUD7B and HNF4α, with a docking score of −258.68 and a confidence score of 0.8979 (Fig. xref A)."

reach
"Molecular docking analysis indicated a potential interaction between OTUD7B and HNF4α, with a docking score of −258.68 and a confidence score of 0.8979 (Fig. 7A)."

sparser
"We used TransDSI to assess whether HNF4α is a deubiquitination substrate of OTUD7B. The TransDSI score for the OTUD7B-HNF4α interaction was 0.7979, suggesting a high probability that HNF4α is a substrate of OTUD7B."

sparser
"Mechanistically, OTUD7B interacts with HNF4α and deubiquitinates it at the K48 site, thereby stabilizing its expression."

sparser
"CoIP further confirmed these findings, demonstrating that OTUD7B directly interacts with HNF4α (Fig. xref B)."
HNF4A decreases the amount of OTUD7B.
1 |
HNF4A decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
HIF1AN affects OTUD7B
5 | 2
HIF1AN binds OTUD7B.
5 |
5 |

No evidence text available

No evidence text available

No evidence text available

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HIF1AN hydroxylates OTUD7B.
| 2
HIF1AN hydroxylates OTUD7B. 2 / 2
| 2

reach
"For instance, hydroxylation of the UBA domain of OTUD7B (Cezanne) by factor inhibiting HIF1 (FIH1) prevents binding to Ub ( Mader et al., 2020 )."

reach
"Finally, the DUB Cezanne (OTUD7B) is hydroxylated by the asparaginyl β-hydroxylase factor inhibiting HIF1 (FIH1) within a domain similar to the Ub-associated domain, and this modification blocks Ub-binding, although the significance of this event remains unknown (172)."
E2F1 affects OTUD7B
7 |
E2F1 decreases the amount of OTUD7B. 7 / 7
7 |

No evidence text available

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No evidence text available
TRAF6 affects OTUD7B
1 2 | 1 1
1 2 | 1 1

No evidence text available

sparser
"One of them is OTUD7B (also known as Cezanne), which interacts with TRAF6 and inhibits NF-κB activation upon overexpression [27,28] ."

No evidence text available

reach
"ZA20D1 can associate with Traf6 and is possibly an antagonist to Traf6."

No evidence text available
TNF affects OTUD7B
| 5
TNF activates OTUD7B.
| 4
TNF activates OTUD7B. 4 / 5
| 4

reach
"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)."

reach
"Cezanne is induced by TNF-α in cultured cells and silencing of Cezanne leads to elevated NFκB activity in response to this cytokine ( Enesa et al., 2008 )."

reach
"Given that Cezanne can be modulated by shear stress, TNFα, IL-1 and reactive oxygen species , future studies should address whether these factors influence inflammatory responses to hypoxia-reoxygenation by altering the expression and/or activity of Cezanne."

reach
"Our subsequent studies revealed that Cezanne can be induced by TNFα, IL-1 and functions as an inhibitor of NF-κB, thus forming a negative feedback loop in inflammatory cytokine signalling , and a recent report indicated that Cezanne can also influence non-canonical NF-κB activation ."
TNF decreases the amount of OTUD7B.
| 1
TNF decreases the amount of OTUD7B. 1 / 1
| 1

reach
"Inhibition of proteasome in TNF-stimulated BMDCs restored TRAF2 levels of OTUD7b-deficient BMDC demonstrating that OTUD7b prevented proteasomal degradation of TRAF2 (Fig. 3C)."
SOX2 affects OTUD7B
3 | 3
3 | 1

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sparser
"Then we detected the interaction between Sox2 and OTUD7B at endogenous (Fig.  xref ) and exogenous (Supplementary Fig.  xref ) levels and mapped the Sox2-binding region of OTUD7B to the C-terminal zinc finger (ZF) domain (Fig.  xref )."
| 2

sparser
"To further confirm the direct binding of Sox2 to OTUD7B ZF domain, we purified recombinant GST-tagged OTUD7B truncates, including GST-OTUD7B-N (1-359), GST-OTUD7B-C (360–843), GST-OTUD7B-△ZF (1–810), and GST-OTUD7B-ZF (811–843) (Fig.  xref )."

sparser
"The result of GST pull-down assay indicated that Sox2 interacted with OTUD7B ZF domain directly in cell-free system (Fig.  xref )."
PIK3C3 affects OTUD7B
4 | 1 1
4 | 1 1

sparser
"CO-IP assay showed that Cezanne could bind PIK3C3 rather than Beclin-1 (Fig. xref )."

reach
"CO-IP assay showed that Cezanne could bind PIK3C3 rather than Beclin-1 (Fig. 3B, C)."

No evidence text available

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OTUD7B affects pathway
| 6
OTUD7B inhibits pathway.
| 5
OTUD7B inhibits pathway. 5 / 5
| 5

sparser
"A previous study showed that OTUD7B can inhibit the NF-κB pathway in liver cancer [ xref ]."

sparser
"To examine the potential mechanism by which OTUD7B inhibits the LCL161-induced NF-κB pathway, we transfected Flag-TRAF3 and HA-OTUD7B, Myc-NIK and HA-OTUD7B into H1299 cells for 48 h."

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

sparser
"The non-canonical pathway can be inhibited by OTUD7B or down-regulated by degradation of NIK."

sparser
"TI 8 , TI 11 , and TI 13 reflect the pathway from receptor stimulation to nuclear translocation, the regulative feedback loop of NIK degradation, and the regulative inhibition by OTUD7B, respectively,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B activates pathway.
| 1
OTUD7B activates pathway. 1 / 1
| 1

sparser
"This prevents miR-137 from binding and suppressing OTUD7B mRNA, resulting in OTUD7B-dependent activation of the EFGR/MAPK pathway."
| 6
| 6

reach
"Cezanne was highly expressed in Osimertinib-resistant cells, and Cezanne overexpression promoted Osimertinib resistance, while chloroquine (CQ), an autophagy inhibitor, reverted this process."

reach
"The IC50 assay also proved the resistance of Osimertinib induced by Cezanne and the addition of CQ significantly decreased the Osimertinib resistance in LUAD cell lines, PC9 and HCC827 cells (Fig. 1F, G), which suggested Cezanne promoted Osimertinib resistance and autophagy played a vital role (Fig. 8)."

reach
"To investigate the connection between Cezanne and Osimertinib resistance in LUAD, analysis of the expression of Cezanne using the GEO data was conducted, which showed that Cezanne expression elevated in the Osimertinib-treated PC9 cells (Fig. 1A) and Osimertinib-resistant HCC827, H1975 cells (Fig. 1B, C)."

reach
"As shown in Fig. 1D and E, Cezanne knockdown with siRNA decreased Osimertinib sensitivity in PC9 and HCC827 cells, while Cezanne-Overexpressing (Cezanne OE) cells developed Osimertinib resistance (Fig. 1F, G)."

reach
"Therefore, our results suggested that Cezanne contributed to Osimertinib resistance in LUAD cells.Autophagy activation is related to Osimertinib resistance in several types of tumors [6], and our study indicated that the autophagy inhibitor CQ could inhibit the Osimertinib resistance induced by Cezanne (Fig. 1F, G), which suggested Cezanne promoted Osimertinib resistance in an autophagy-dependent way."

reach
"Cezanne promoted Osimertinib resistance by accelerating EGFR recycling."
OTUD7B affects migration
| 6
OTUD7B inhibits migration. 6 / 6
| 6

eidos
"* 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 ."

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

eidos
"However , whether OTUD7B can inhibit LCL161-induced invasion and migration and be used to select a target population in LCL161 treatment for lung cancer is unclear ."

eidos
"OTUD7B suppresses Smac mimetic-induced lung cancer cell invasion and migration via deubiquitinating TRAF3 Background Smac mimetics are a type of drug that can induce apoptosis by antagonizing IAP family members in cancer treatment ."

eidos
"Moreover , OTUD7B inhibits LCL161-induced invasion and migration by binding to and deubiquitinating TRAF3 , thereby inhibiting NIK and preventing non-canonical NF-kappaB activation ."

eidos
"Furthermore , OTUD7B can inhibit LCL161-induced lung cancer cell invasion and migration by deubiquitinating TRAF3 , inhibiting NIK and preventing non-canonical NF-kappaB activation ."
OTUD7B affects Ubiquitin
| 1 5
OTUD7B binds Ubiquitin.
| 5

sparser
"Cezanne is hydroxylated at Asn35 of the UBA domain in an oxygen- or FIH1-dependent manner, which inhibits the binding of Ub to Cezanne ( xref )."

sparser
"Upon binding of the proximal ubiquitin, the prereactive conformation and active state are reached via strong electrostatic interactions between the Cezanne-1 residue Glu157 and Lys33 of PRO ubiquitin."

sparser
"Downstream of RNF8/RNF168, the DUB Cezanne in complex with Cezanne2 binds to K63-linked ubiquitin chains at the sites of damage and removes K11-linked ubiquitination from mixed polyUb chains as well."

sparser
"DUB linkage specificity relies on careful positioning of the proximal Ub, which interacts with Cezanne via an unusual surface, involving Thr12, Glu16 and its α-helix (Asp32, Lys33, Glu34, Gly35) ( xref , xref )."

sparser
"The strong electrostatic interaction between the Cezanne-1 residue Glu157 and Lys33 of PRO ubiquitin is persistent and stabilizes the substrate positioning relative to the catalytic residues."
OTUD7B inhibits Ubiquitin.
| 1
| 1

reach
"Notably, in the presence of MG132, the protein level of HNF4α was not affected by OTUD7B, suggesting that OTUD7B inhibits HNF4α degradation via ubiquitin–proteasome system."
OTUD7B affects MLST8
2 | 2 2
OTUD7B binds MLST8.
2 | 1 2
2 | 1 2

reach
"Reduced GbetaL ubiquitination was largely due to induced binding of OTUD7B to GbetaL, but not loss of TRAF2 binding (XREF_FIG and XREF_FIG)."

sparser
"Reduced GβL ubiquitination was largely due to induced binding of OTUD7B to GβL, but not loss of TRAF2 binding ( xref and xref )."

No evidence text available

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sparser
"Furthermore, 7Bi did not significantly affect OTUD7B protein levels in A549 and HEK293 cells ( xref E,F), nor significantly affected OTUD7B binding to GβL ( xref )."
OTUD7B activates MLST8.
| 1
OTUD7B activates MLST8. 1 / 1
| 1

reach
"Additionally, OTUD7B, but not UCH-L1, a DUB for RPTOR 24, targeted GbetaL for deubiquitination (XREF_FIG)."
OTUD7B affects Flag
| 6
| 6

sparser
"Concordantly, the ubiquitination level of N1ICD was dramatically attenuated in the Flag-OTUD7B group, whereas the N1ICD ubiquitination level was restored in the Flag-OTUD7B-C194S group (Fig. xref )."

sparser
"Upon H 2 O 2 treatment, we found that exogenously expressed C-terminally epitope-tagged human Cezanne (Cezanne-Flag) was labeled by DCP-Bio1 in cell lysates ( xref ), suggesting that Cezanne was oxidized to the sulfenic acid intermediate in response to oxidative stress."

sparser
"Further IP experiments showed that both Flag-OTUD7B and Flag-p53 were able to co-precipitate the endogenous forms of p53 and OTUD7B in 293T cells, respectively (Figure xref E)."

sparser
"Flag-USP4, Flag-SENP2, Flag-USP22, Flag-OTUD7B, Flag-USP11, Flag-UCHL1, Flag-USP5WT GST-USP5 WT , GST-USP5 C119A , His-OCT4, HA-Ub, HA-Ub-Lys0, HA-Ub-Lys48, and HA-Ub-Lys63 overexpression plasmids wer[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The N1ICD level was profoundly upregulated in the OTUD7B wild-type (Flag-OTUD7B) group, but it was restored by the catalytically inactive mutant C194S of OTUD7B (Flag-OTUD7B-C194S) (Fig. xref )."

sparser
"Similarly, upon transfecting HEK293T cells with Flag-OTUD7B, His- HNF4α, and HA-Ub, we observed that OTUD7B stabilized HNF4α protein levels (Fig. xref E)."
YAP1 affects OTUD7B
3 | 1 1
3 | 1 1

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reach
"Co-immunoprecipitation (Co-IP) and ubiquitination assays showed the interaction of OTUD7B and YAP1."

sparser
"Co-immunoprecipitation (Co-IP) and ubiquitination assays showed the interaction of OTUD7B and YAP1."
Ubiquitin affects OTUD7B
| 5

sparser
"Cezanne is hydroxylated at Asn35 of the UBA domain in an oxygen- or FIH1-dependent manner, which inhibits the binding of Ub to Cezanne ( xref )."

sparser
"Upon binding of the proximal ubiquitin, the prereactive conformation and active state are reached via strong electrostatic interactions between the Cezanne-1 residue Glu157 and Lys33 of PRO ubiquitin."

sparser
"Downstream of RNF8/RNF168, the DUB Cezanne in complex with Cezanne2 binds to K63-linked ubiquitin chains at the sites of damage and removes K11-linked ubiquitination from mixed polyUb chains as well."

sparser
"DUB linkage specificity relies on careful positioning of the proximal Ub, which interacts with Cezanne via an unusual surface, involving Thr12, Glu16 and its α-helix (Asp32, Lys33, Glu34, Gly35) ( xref , xref )."

sparser
"The strong electrostatic interaction between the Cezanne-1 residue Glu157 and Lys33 of PRO ubiquitin is persistent and stabilizes the substrate positioning relative to the catalytic residues."
TFDP1 affects OTUD7B
5 |
TFDP1 decreases the amount of OTUD7B. 5 / 5
5 |

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OTUD7B affects mTORC2
| 4 1
OTUD7B activates mTORC2. 5 / 5
| 4 1

reach
"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]"

sparser
"For example, OTUD7B activates mTORC2 by deubiquitinating and removing polyubiquitin chains from GβL, promoting its interaction with SIN1, which enhances AKT signaling and thereby contributes to lung tumorigenesis [ xref ]."

reach
"mTOR is the catalytic subunit of two complexes, mTORC1 and mTORC2.65 mTORC1 comprises mTOR, a regulatory protein associated with mTOR (Raptor) and mammalian lethal with Sec13 protein 8 (mLST8, also referred to as GβL).65 In contrast, mTORC2 comprises mTOR, rapamycin insensitive companion of mTOR (Rictor), and GβL.65 Otud7b has been reported to promote mTORC2 signaling through the deubiquitination of GβL."

reach
"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."

reach
"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."
| 3

reach
"Otud7b positively regulates Th1 cell differentiation by facilitating TCR signaling and early induction of IFN-γ [135] ."

reach
"COP1 knockdown stabilizes Sox2 and prevents differentiation, while OTUD7B knockdown destabilizes Sox2 and induces differentiation."

reach
"Otud7b mediates T cell activation and differentiation in vitro."

reach
"Otud7b deficiency attenuated TCR-CD28-stimulated activation of Zap70 and downstream signaling factors and impaired T cell activation and Th1 cell differentiation."

reach
"In support, OTUD7B depletion in NSCs induces differentiation (71)."
OTUD7B affects Wnt
| 1 4
OTUD7B activates Wnt.
| 1 2
OTUD7B activates Wnt. 3 / 3
| 1 2

eidos
"Screening candidate DUBs from the human DUB library , we discovered that OTUD7B interacts with LEF1 and activates Wnt signaling ."

reach
"As a result, we hypothesized that OTUD7B promotes Wnt signaling by facilitating the nuclear localization of LEF1 and/or its interaction with β-catenin within the nucleus."

reach
"Screening candidate DUBs from the human DUB library, we discovered that OTUD7B interacts with LEF1 and activates Wnt signaling."
OTUD7B increases the amount of Wnt.
| 2
OTUD7B increases the amount of Wnt. 2 / 2
| 2

reach
"This finding clearly demonstrates that OTUD7B mediates the activation of Wnt target gene expression."

reach
"OTUD7B Upregulates the Expression of Wnt Target Genes."
| 1 4

eidos
"OTUD7B is a novel DUB of the YAP1 pathway and accelerates GC progression ."

reach
"Moreover, OTUD7B overexpression promoted GC cell proliferation and metastasis both in vitro and in vivo, whereas OTUD7B knockdown exhibited opposing biological effects."

reach
"In vitro assays revealed that genetic knockout of OTUD7B markedly reduced the migration and invasion of GC cells, while overexpression of OTUD7B led to enhanced cellular migration and invasion."

reach
"OTUD7B is a novel DUB of the YAP1 pathway and accelerates GC progression."

reach
"Mechanistically, OTUD7B likely promotes GC metastasis through the WNT signaling pathway, specifically targeting β-catenin."
OTUD7B affects MAPK
| 4 1
OTUD7B activates MAPK.
| 3 1
OTUD7B activates MAPK. 4 / 4
| 3 1

reach
"This prevents miR-137 from binding and suppressing OTUD7B mRNA, resulting in OTUD7B dependent activation of the EFGR and MAPK pathway."

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

sparser
"Therefore, we hypothesized that OTUD7B may deubiquitinate EGFR and activate downstream pathway MAPK."

reach
"DC-specific OTUD7b augments NF-kappaB and MAP kinase signaling by stabilizing TRAF2."
OTUD7B decreases the amount of MAPK.
| 1
OTUD7B decreases the amount of MAPK. 1 / 1
| 1

reach
"qRT-PCR illustrated that miR-137 downregulated promotes the mRNA express level of MAPK target genes (CyclinD1, CDK2, MMP2, MMP9), Linc00976 and OTUD7B downregulating could reverse the effect in Linc00976U PC cells (Fig. 7g)."
OTUD7B affects KLF4 protein
| 5
OTUD7B activates KLF4 protein. 5 / 5
| 5

eidos
"We show here that OTUB7B upregulates the level of KLF4 protein , a stem cell pluripotency protein 41 , through interacting with and deubiquitylating KLF4 , a repressor of VSMC differentiation , whereas OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein level ."

eidos
"KLF4 negatively regulates NMHC IIA expression , and downregulation of KLF4 by Sal-miR-1 and 3 reduces KLF4 repression of the expression of NMHC IIA and thus increases NMHC IIA expression level Because Sal-miR-1 and 3 downregulated KLF4 protein levels by attenuating OTUD7B expression , we sought to determine KLF4 target genes associated with induction of VSMC migration ."

eidos
"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 ."

eidos
"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 ."

eidos
"Our findings reveal , for the first time , that OTUD7B upregulates the level of KLF4 protein through interacting with and deubiquitylating KLF4 ."
OTUD7B affects HYCC1
| 5
OTUD7B activates HYCC1.
| 3
OTUD7B activates HYCC1. 3 / 3
| 3

reach
"Together these findings suggest that the phenotypic changes in HCC cells elicited by OTUD7B rely on the downstream actions of p53."

reach
"Other phenotypic features consistent with apoptosis observed upon overexpressing OTUD7B in HCC cells were the condensation and fragmentation of nuclear chromatin 49 as detected by flow cytometry and confocal microscopy, respectively (Figure 7F-G), while examination of cleaved caspase 3 staining in HCC xenografts showed that OTUD7B overexpression also increased HCC cell apoptosis rates in vivo (Figure 7H)."

reach
"This study represents one of several reports showing both negative and positive effects of OTUD7B on tumor cell invasiveness 18, 23, 42, 63, a tumorigenic phenotype which we have not addressed here.We further observed one of the major outcomes associated with the stabilization of p53 via enforced OTUD7B expression involved inducing HCC cell apoptosis, phenocopying the p53 response to cellular insults such as unresolved levels of DNA damage."
OTUD7B inhibits HYCC1.
| 2
OTUD7B inhibits HYCC1. 2 / 2
| 2

reach
"Foremost, we showed that increasing OTUD7B expression accentuated p53 expression, causing growth inhibition while its knockdown promoted HCC cell growth both in vitro and in vivo."

reach
"However, in hepatocellular carcinoma (HCC), OTUD7B may function as a tumor suppressor, which is evidenced by the fact that OTUD7B knockdown accelerates the migration and invasion of HCC cells in vitro and promotes metastasis in vivo."
OTUD7B affects HIF1AN
5 |
5 |

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OTUD7B affects Fibrosis
| 5
| 5

reach
"Gene set enrichment analysis showed that fibrosis, heart function, and protein processing‐related pathways were all activated by OTUD7B deficiency (Figure 5B)."

reach
"Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery-induced myocardial hypertrophy, abnormal cardiac function, and fibrosis."

reach
"Histological examinations using H&E (Fig. 2G), WGA (Fig. 2H), Masson (Fig. 2J, K), and Sirius Red staining (Fig. 2L, M) consistently indicated that OTUD7B knockdown significantly intensified pressure overload-induced cardiac hypertrophy and fibrosis."

reach
"Collectively, these findings demonstrate that OTUD7B knockdown exacerbates pressure overload-induced myocardial hypertrophy and fibrosis, leading to deteriorated cardiac function."

reach
"These data provided further evidence that OTUD7B deficiency promotes cardiac remodeling and fibrosis."
OTUD7B affects Cebpb
| 5
| 5

sparser
"The luciferase reporter containing wildtype TCF/LEF binding sites (TOPflash) and mutated TCF/LEF binding sites (FOPflash) was transfected with SFB-USP36 or SFB-OTUD7B. Compared to FOPflash luciferase levels, both USP36 and OTUD7B increased the luciferase activities (TOPflash), but OTUD7B significantly enhanced LEF1 activity to a greater extent (6.64-fold) than USP36 did (2.04-fold) ( xref C)."

sparser
"We prepared cDNA samples from HEK293T cells transiently transfected with either SFB-GFP (control) or SFB-OTUD7B, and performed qPCR analysis."

sparser
"We co-transfected these constructs and full-length SFB-OTUD7B into HEK293T cells and pulled down SFB-OTUD7B with S-protein agarose beads."

sparser
"Next, we generated three deletion mutants of OTUD7B: OTUD7BΔZnF (Zinc Finger domain deleted, aa 1-1077), OTUD7BΔOTU (Ovarian Tumor domain deleted, aa 1-564 & 1078-2532), and OTUD7BNt (UBA domain-containing, 1-564) using the SFB-OTUD7B plasmid ( xref C) and attempted to identify the LEF1-binding region on OTUD7B. Similarly, we co-transfected these constructs and full-length MYC-LEF1 into HEK293T cells and pulled down full-length and mutant SFB-OTUD7B with S-protein agarose beads."

sparser
"To investigate this, we co-transfected MYC-LEF1 with SFB-OTUD7B or SFB-GFP plasmids into HEK293T cells and separated the cytoplasmic and nuclear fractions of the cell lysates."
OTUD7B affects AURKA
5 |
5 |

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OTUD7B affects 5a
| 2 3
| 2 3

reach
"Taken together, these results suggest that HCV NS5A protein interacts with OTUD7B, thereby modulating its DUB activity."

sparser
"Taken together, these results suggest that HCV NS5A protein interacts with OTUD7B, thereby modulating its DUB activity."

sparser
"Co-immunoprecipitation analyses showed that NS5A interacts with OTUD7B in both Huh-7 and HCV RNA replicon cells."

sparser
"Either V121A or V124A mutation in NS5A disrupts the NS5A-OTUD7B interaction."

reach
"Co-immunoprecipitation analyses showed that NS5A interacts with OTUD7B in both Huh-7 and HCV RNA replicon cells."
MLST8 affects OTUD7B
2 | 1 2
2 | 1 2

reach
"Reduced GbetaL ubiquitination was largely due to induced binding of OTUD7B to GbetaL, but not loss of TRAF2 binding (XREF_FIG and XREF_FIG)."

sparser
"Reduced GβL ubiquitination was largely due to induced binding of OTUD7B to GβL, but not loss of TRAF2 binding ( xref and xref )."

No evidence text available

No evidence text available

sparser
"Furthermore, 7Bi did not significantly affect OTUD7B protein levels in A549 and HEK293 cells ( xref E,F), nor significantly affected OTUD7B binding to GβL ( xref )."
IRF3 affects OTUD7B
2 | 3
2 | 3

sparser
"OTUD7B directly interacts with IRF3 and activates p62 by removing K63 polyubiquitin chains leading to enhanced p62 oligomerization."

sparser
"Mechanistically, OTUD7B interacts with IRF3, and activates IRF3-associated cargo receptor SQSTM1/p62 (sequestosome 1) by removing its K63-linked poly-ubiquitin chains at lysine 7 (K7) to enhance SQSTM1 oligomerization."

No evidence text available

No evidence text available

sparser
"RNF26 played a role in EGFR‐driven cell proliferation by ubiquitinating Sqstm1, [ xref ] while mutation of Sqstm1 at K420 led to abnormal ubiquitination and thus inhibited autophagy. [ xref ] TRIM21 could bind to the PB1 domain to ubiquitinate K7, hindering the oligomerization of Sqstm1 and inhibiting its function. [ xref ] CUL5‐ASB6 complex promoted the ubiquitination of Sqstm1 for degradation to inhibit cell proliferation and autophagy. [ xref ] In addition, RNF166 and NEDD4 activated autophagy through ubiquitination of Sqstm1. [ xref ] KEAP1‐CUL3 ubiquitinated Sqstm1 at the site of K420 within the UBA domain, improved the efficiency of substrate transport to the autophagosome, enhanced selective autophagic flux, and accelerated the degradation of target proteins. [ xref ] The ubiquitin‐specific peptidase USP8 acted as a negative regulator of autophagy by deubiquitinating Sqstm1 at K420. [ xref ] The deubiquitinating enzyme OTUD7B interacted with IRF3 to remove the polyubiquitin chain at the K7 site of Sqstm1 to enhance the oligomerization for the block of antiviral immune response. [ xref ] In this study, we found that RNF6, an E3 ubiquitin ligase, mediated the ubiquitination of Sqstm1 at K314 to promote autophagy."
Cebpb affects OTUD7B
| 5
| 5

sparser
"The luciferase reporter containing wildtype TCF/LEF binding sites (TOPflash) and mutated TCF/LEF binding sites (FOPflash) was transfected with SFB-USP36 or SFB-OTUD7B. Compared to FOPflash luciferase levels, both USP36 and OTUD7B increased the luciferase activities (TOPflash), but OTUD7B significantly enhanced LEF1 activity to a greater extent (6.64-fold) than USP36 did (2.04-fold) ( xref C)."

sparser
"We prepared cDNA samples from HEK293T cells transiently transfected with either SFB-GFP (control) or SFB-OTUD7B, and performed qPCR analysis."

sparser
"We co-transfected these constructs and full-length SFB-OTUD7B into HEK293T cells and pulled down SFB-OTUD7B with S-protein agarose beads."

sparser
"Next, we generated three deletion mutants of OTUD7B: OTUD7BΔZnF (Zinc Finger domain deleted, aa 1-1077), OTUD7BΔOTU (Ovarian Tumor domain deleted, aa 1-564 & 1078-2532), and OTUD7BNt (UBA domain-containing, 1-564) using the SFB-OTUD7B plasmid ( xref C) and attempted to identify the LEF1-binding region on OTUD7B. Similarly, we co-transfected these constructs and full-length MYC-LEF1 into HEK293T cells and pulled down full-length and mutant SFB-OTUD7B with S-protein agarose beads."

sparser
"To investigate this, we co-transfected MYC-LEF1 with SFB-OTUD7B or SFB-GFP plasmids into HEK293T cells and separated the cytoplasmic and nuclear fractions of the cell lysates."
AURKA affects OTUD7B
5 |
5 |

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5a affects OTUD7B
| 2 3
| 2 3

reach
"Taken together, these results suggest that HCV NS5A protein interacts with OTUD7B, thereby modulating its DUB activity."

sparser
"Taken together, these results suggest that HCV NS5A protein interacts with OTUD7B, thereby modulating its DUB activity."

sparser
"Co-immunoprecipitation analyses showed that NS5A interacts with OTUD7B in both Huh-7 and HCV RNA replicon cells."

sparser
"Either V121A or V124A mutation in NS5A disrupts the NS5A-OTUD7B interaction."

reach
"Co-immunoprecipitation analyses showed that NS5A interacts with OTUD7B in both Huh-7 and HCV RNA replicon cells."
P38 affects OTUD7B
| 1 3
P38 activates OTUD7B. 4 / 4
| 1 3

reach
"Here we describe a novel form of cross-talk between the NF-κB and MAP kinase pathways where p38-dependent induction of Cezanne during hypoxia suppresses NF-κB activity."

eidos
"We examined the mechanism of Cezanne induction by p38 , which is known to influence gene expression via members of the activating transcription factor ( ATF ) family and also by enhancing mRNA stability25 ."

reach
"P38 also enhanced the stability of Cezanne transcripts in hypoxic EC as pharmacological inhibition of p38 using SB202190 destabilized Cezanne mRNA in actinomycin D chase experiments (Online Fig. V)."

reach
"Thus we conclude that p38 induces Cezanne through both transcriptional and post-transcriptional mechanisms."
SQSTM1 affects OTUD7B
3 | 1
3 | 1

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sparser
"LSD1 protein expression oscillates during cell cycle, low in G1 and high in G2/M. [ xref ] Similar expression patterns were observed with OTUD7B. [ xref ] We therefore set out to investigate if OTUD7Bp62 axis is responsible for LSD1 ubiquitination and degradation throughout the cell cycle."
POLR2A affects OTUD7B
| 2 2
| 2 2

sparser
"CO-IP assay in Hek 293T cells, IP with anti-Cezanne, validated the binding of Cezanne and POLR2A (Fig. xref )."

reach
"However, the public CHIP data from the Cistrome project (http://cistrome.org/) showed that POLR2A, rather than CTCF, binds the transcription start site of PIK3C2A (Fig. 5K) and we chose POLR2A as the candidate TF.CO-IP assay in Hek 293T cells, IP with anti-Cezanne, validated the binding of Cezanne and POLR2A (Fig. 5L)."

reach
"Indeed, Cezanne could bind and stabilize POLR2A and deubiquitinate the K48-linked ubiquitination of POLR2A (Fig. 5L–N)."

sparser
"In this study, with the help of a public database and LC-MS/MS analysis, we identified a transcription factor, called POLR2A, which might be the mediator between Cezanne and PIK3C2A. Indeed, Cezanne could bind and stabilize POLR2A and deubiquitinate the K48-linked ubiquitination of POLR2A (Fig. xref )."

reach
"Our findings suggest that OTUD7B downregulation significantly suppresses fatty acid metabolism and promotes ferroptosis."

reach
"OTUD7B knockdown causes a reprogramming of fatty acid metabolism in pathological cardiac hypertrophy."

reach
"Overexpression of HNF4α significantly alleviated the effects of OTUD7B knockdown, which exacerbated ferroptosis and suppressed fatty acid metabolism."

reach
"Additionally, HNF4α overexpression enhanced the expression of FAO genes (Acot1, Cd36, Cpt2, Crat, Cpt1b, and Acadm), rescuing the suppression of fatty acid metabolism induced by OTUD7B knockdown (Fig. 8K)."
| 4
| 4

reach
"Instead, in the absence of Cezanne, HA K11-linked ubiquitin (an HA-tagged ubiquitin K11 mutant in which all of the lysine residues except lysine 11 are mutated to arginine) conjugation increased, consistent with a role of Cezanne DUB activity in antagonizing K11-conjugation on damaged chromatin (Fig. 4C; Paul and Wang 2017)."

reach
"This is consistent with our previous finding that Cezanne antagonizes RNF8 and Ube2S-dependent K11-conjugation on damaged chromatin (Paul and Wang 2017)."

reach
"Since it has been shown that Cezanne K11-DUB activity not only functions toward K11-chains but also extends to K11-linkage within K11/K63- and K11/Lys48-branched chains (Mevissen et al. 2016), it is likely that at least one of the functions of Cezanne is to prevent K11-conjugation on K63-chains forming mixed K63/K11-chains to protect the “purity” of K63-chains."

reach
"Cezanne deficiency increases K11-ubiquitin conjugation but does not affect K63- conjugation at DNA damage sites."
OTUD7B affects UBE2S
1 | 3
OTUD7B inhibits UBE2S.
| 3
OTUD7B inhibits UBE2S. 3 / 3
| 3

reach
"In response to DSBs, Cezanne antagonizes the activity of RNF8 and Ube2S in K11-linkage ubiquitin modification of chromatin-bound proteins, including H2A/H2AX, on damaged chromatin (Paul and Wang 2017)."

reach
"In response to DSB, Cezanne antagonizes the activity of RNF8 and UBE2S [146] ."

reach
"This is consistent with our previous finding that Cezanne antagonizes RNF8 and Ube2S-dependent K11-conjugation on damaged chromatin (Paul and Wang 2017)."
OTUD7B binds UBE2S.
1 |
1 |

No evidence text available
OTUD7B affects RNF8
| 4
OTUD7B inhibits RNF8. 4 / 4
| 4

reach
"This is consistent with our previous finding that Cezanne antagonizes RNF8 and Ube2S-dependent K11-conjugation on damaged chromatin (Paul and Wang 2017)."

reach
"In response to DSB, Cezanne antagonizes the activity of RNF8 and UBE2S [146] ."

reach
"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."

reach
"In response to DSBs, Cezanne antagonizes the activity of RNF8 and Ube2S in K11-linkage ubiquitin modification of chromatin-bound proteins, including H2A/H2AX, on damaged chromatin (Paul and Wang 2017)."
OTUD7B affects POLR2A
| 2 2
| 2 2

sparser
"CO-IP assay in Hek 293T cells, IP with anti-Cezanne, validated the binding of Cezanne and POLR2A (Fig. xref )."

reach
"However, the public CHIP data from the Cistrome project (http://cistrome.org/) showed that POLR2A, rather than CTCF, binds the transcription start site of PIK3C2A (Fig. 5K) and we chose POLR2A as the candidate TF.CO-IP assay in Hek 293T cells, IP with anti-Cezanne, validated the binding of Cezanne and POLR2A (Fig. 5L)."

reach
"Indeed, Cezanne could bind and stabilize POLR2A and deubiquitinate the K48-linked ubiquitination of POLR2A (Fig. 5L–N)."

sparser
"In this study, with the help of a public database and LC-MS/MS analysis, we identified a transcription factor, called POLR2A, which might be the mediator between Cezanne and PIK3C2A. Indeed, Cezanne could bind and stabilize POLR2A and deubiquitinate the K48-linked ubiquitination of POLR2A (Fig. xref )."
OTUD7B affects IGF1R
2 1 | 1
OTUD7B binds IGF1R.
2 | 1
2 | 1

sparser
"Methods: Co-Immunoprecipitation assay was performed to investigate the interactions between Cezanne and IGF-1R. A xenograft model was established to assess the efficacy of Cezanne on cancer progression in vivo."

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OTUD7B deubiquitinates IGF1R.
1 |
OTUD7B deubiquitinates IGF1R. 1 / 1
1 |

"Conclusion: Mechanistically, <span class="match term0">Cezanne</span> directly targets <span class="match term1">IGF-1R</span> by deubiquitination and stabilization"
| 4

reach
"OTUD7b stabilizes TRAF2 by cleaving K48-linked polyubiquitin chains and prevents DC apoptosis."

reach
"However, combined pharmacological inhibition of RIPK1 activity (Nec1s) and apoptosis (zVAD-FMK) completely rescued survival of OTUD7b-deficient BMDC in vitro and in vivo indicating that OTUD7b inhibits RIPK1-independent and to a lesser extent RIPK1-dependent DC apoptosis [43]."

reach
"DC-specific OTUD7b prevents DC death and protects mice from ECM."

reach
"OTUD7b prevents DC death in human monocyte-derived DCs."
| 3
OTUD7B inhibits Cell Survival.
| 1

reach
"Among those tested including the apoptosis inhibitor Z-VAD-FMK (Z-VAD), the programmed necrosis inhibitor necrostatin-1 (Nec-1), the ferroptosis inhibitor ferrostatin-1 (Ferr-1), the necroptosis inhibitor Disulfiram, the cuproptosis inhibitor tetrathiomolybdate (TTM), and the autophagy inhibitor CQ; however, cell viability reductions caused by OTUD7B overexpression were only restored by the addition of the apoptosis inhibitor Z-VAD (Figure 7A-B)."
OTUD7B activates Cell Survival.
| 2

reach
"OTUD7B knockdown gradually reduced the cell viability rate over time."

reach
"Bin Wang et al. reported that genetic deletion of Cezanne in mice suppressed AKT activation in vivo , suggesting that Cezanne might activate AKT to protect cell survival( Wang et al., 2017 )."
Mice affects OTUD7B
| 4
Mice inhibits OTUD7B. 4 / 4
| 4

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"Both AAV9-shNC and AAV9-shOTUD7B mice showed significant reductions in HNF4α levels after TAC when compared to sham groups Moreover, OTUD7B knockdown mice exhibited a more robust decrease in HNF4α expression following TAC compared to AAV9-shNC mice (Fig. 5E, F)."

reach
"Representative heart images further demonstrated enlarged hearts in OTUD7B knockdown mice compared to wild-type controls post-TAC (Fig. 2D)."

reach
"Body weight remained unchanged across the four groups (Figure S2A); however, heart weight, along with heart weight/body weight (HW/BW) and heart weight/tibia length (HW/TL) ratios, significantly increased in OTUD7B knockdown mice after TAC (Figure S2B, 2E, F)."

reach
"Concordant with the histological and echocardiographic findings, protein levels of BNP (brain natriuretic peptide), COL3A1 (collagen type III alpha 1), and mRNA expressions of Bnp, Myh7 (myosin heavy chain 7), and Col3a1 were markedly elevated in OTUD7B knockdown mice post-TAC (Fig. 2N, O)."
HIF1A affects OTUD7B
1 | 3
1 | 3

sparser
"These findings support the interaction between OTUD7B and HIF-1α ( xref )."

sparser
"HA-HIF-1α co-immunoprecipitated with FLAG-OTUD7B, while the reciprocal Co-IP also confirmed the association of HIF-1α with OTUD7B. These findings definitively established the interaction between OTUD7B and HIF-1α ( xref )."

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sparser
"Next, Co-IP assays were performed to evaluate the interactions between the endogenous OTUD7B and HIF-1α."
F2 affects OTUD7B
| 2 2
F2 activates OTUD7B. 4 / 4
| 2 2

reach
"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."

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

eidos
"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 ) ."

eidos
"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 ) ."
EGFR affects OTUD7B
1 | 1 2
1 | 1 2

sparser
"Subsequently, the interaction between OTUD7B and EGFR was confirmed by co-immunoprecipitation and immunofluorescent staining (Fig. xref b, c)."

No evidence text available

reach
"Subsequently, the interaction between OTUD7B and EGFR was confirmed by co-immunoprecipitation and immunofluorescent staining (Fig. 6b, c)."

sparser
"The results presented in xref confirmed that Cezanne-1 overexpression associates with remarkably reduced ubiquitination of EGFR, as well as with stabilization the receptor and an increase in auto-phosphorylation."
| 2 1
Sulforaphane increases the amount of OTUD7B. 3 / 3
| 2 1

reach
"Furthermore, an up-regulated expression of Cezanne induced by SFN was found in our study."

reach
"In this study, we observed that SFN significantly increased Cezanne protein expression, and down-regulated TRAF6, RIP1 protein expression and inhibited NF-κB pathway after LPS treatment."

sparser
"Furthermore, an up-regulated expression of Cezanne induced by SFN was found in our study."
MiR-500 affects OTUD7B
| 3
MiR-500 inhibits OTUD7B. 3 / 3
| 3

reach
"In gastric cancer cell lines, miR-500 directly repressed CYLD, OTUD7B, and the A20 complex component TAX1BP1 which led to sustained NF-kappaB activation [XREF_BIBR]."

reach
"Taken together, our results suggest that miR-500 overexpression activates the NF-kappaB signalling pathway by repressing CYLD, TAX1BP1, and OTUD7B, and consequently results in gastric cancer aggressiveness and poor clinical outcomes."

reach
"Notably, miR-500 also activates NF-κB signaling by directly repressing two other negative regulators of NF-κB, OTUD7B, and TAX1BP1 [69]."
3 |
Bisphenol A increases the amount of OTUD7B. 3 / 3
3 |

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| 3
OTUD7B binds.
| 2
| 2

sparser
"We obtained 16 DUBs, including eight from the USP family (USP2, USP7, USP8, USP10, USP14, USP15, USP25, and CYLD), one from the UCH family (UCHL3), two from the Josephin family (Ataxin-3 and JOSD2), and five from the OTU family (OTUB2, OTULIN, Cezanne-OTUD7B, OTUD2, and OTUD7C)."

sparser
"For Cezanne-OTUD7B, all probes labeled the enzyme with similar high efficiency ( xref D iii)."
OTUD7B translocates.
| 1
OTUD7B translocates to the nucleus. 1 / 1
| 1

sparser
"We further investigated whether the increased nuclear translocation of LEF1 by OTUD7B leads to enhanced transcriptional activity by promoting the interaction between LEF1 and β-catenin."

reach
"Various E3 ubiquitin ligases and deubiquitinases (DUBs), including Pellino 1, Itch, c-Cbl, Cbl-b, GRAIL, and OTUD7B, have been identified to negatively regulate TCR-CD28 signal transduction and preven[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Further mechanistic studies reveal that OTUD7B associates with RASGRF1 and PLCE1 to disrupt RAS signaling pathway."

reach
"Taken together, OTUD7B promotes the proliferation, and autophagy, and inhibits apoptosis of prostate cancer cells via the AKT/mTOR signaling pathway."
OTUD7B affects set1
| 3
OTUD7B demethylates set1.
| 2
OTUD7B leads to the demethylation of set1 at position 4. 1 / 1
| 1

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"OTU deubiquitinase 7B (OTUD7B) deubiquitinates lysine-specific demethylase 1 (LSD1) to decrease histone H3 lysine 4 (H3K4)/H3K9 methylation, thereby sustaining breast cancer metastasis potential 103.Overexpression of miR-7 in BCSCs decreases endothelial cell adhesion molecule (ESAM) expression by targeting RelA and inhibits tumorigenesis and distant lung metastasis 104."
OTUD7B leads to the demethylation of set1 on lysine. 1 / 1
| 1

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"OTU deubiquitinase 7B (OTUD7B) deubiquitinates lysine-specific demethylase 1 (LSD1) to decrease histone H3 lysine 4 (H3K4)/H3K9 methylation, thereby sustaining breast cancer metastasis potential 103.Overexpression of miR-7 in BCSCs decreases endothelial cell adhesion molecule (ESAM) expression by targeting RelA and inhibits tumorigenesis and distant lung metastasis 104."
OTUD7B methylates set1.
| 1
OTUD7B leads to the methylation of set1. 1 / 1
| 1

reach
"Consequently, OTUD7B deficiency impairs genome-wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis."
| 2

reach
"Inhibition of the NF-κB pathway ameliorated cone degeneration and neuronal cell death caused by the loss of Otud7b in the retina and Otud7b knockdown in cultured cells, respectively."

reach
"To test this hypothesis, we examined the effects of curcumin, an inhibitor of the NF-κB pathway, on neuronal cell death induced by Otud7b knockdown under stress conditions."
| 1

reach
"Furthermore, inhibition of NF-kappaB attenuated cone photoreceptor degeneration in the light-exposed Otud7b -/- retina and stress-induced neuronal cell death resulting from Otud7b deficiency."
OTUD7B affects miR-500
| 3
OTUD7B activates miR-500. 3 / 3
| 3

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"Importantly, the repressive effect of antagomiR-500 on NF-kappaB activity and BCL2L1, CCND1 expression were potently antagonised by individual silencing of CYLD, TAX1BP1, or OTUD7B (XREF_SUPPLEMENTARY), indicating that CYLD, TAX1BP1, and OTUD7B are functionally relevant effectors of miR-500 in NF-kappaB activation."

reach
"Taken together, our results demonstrate that CYLD, TAX1BP1, and OTUD7B are bona fide targets of miR-500."

reach
"Using the TargetScan program, we found that CYLD, OTUD7B, and the A20 complex component TAX1BP1, which function as critical negative regulatory genes by deconjugating K63-polyubiquitin chains from RIP1 [XREF_BIBR, XREF_BIBR], might be potential targets of miR-500."
OTUD7B affects miR-1180
| 3
OTUD7B inhibits miR-1180. 3 / 3
| 3

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"As predicted, western blotting revealed that the expression of OTUD7B, TNIP2 and BAD decreased in HepG2 and Huh7 cells overexpressing miR-1180, and expression increased in cells transfected with the miR-1180 inhibitor compared to negative controls (XREF_FIG)."

reach
"We also indicate a mechanism for miR-1180 induced drug resistance by downregulation of OTUD7B, TNIP2 and BAD, the direct targets of miR-1180 in HCC cells."

reach
"Collectively, the results revealed that OTUD7B, TNIP2 and BAD are direct targets of miR-1180, and are subsequently downregulated in HCC cells overexpressing miR-1180."
| 3
OTUD7B inhibits ferroptosis.
| 2
| 2

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"OTUD7B knockdown resulted in ferroptosis, as evidenced by decreased mitochondrial cristae, increased Fe 2+ ion content, lipid peroxide accumulation, while OTUD7B overexpression inhibited ferroptosis."

reach
"OTUD7B overexpression attenuates ferroptosis."
OTUD7B activates ferroptosis.
| 1
| 1

reach
"Our findings suggest that OTUD7B downregulation significantly suppresses fatty acid metabolism and promotes ferroptosis."
OTUD7B affects cell death
| 1
| 1

reach
"We also found that Otud7b knockdown in cultured neuronal cells subjected to serum starvation increased cell death."
OTUD7B affects PIK3C2A
| 3
OTUD7B increases the amount of PIK3C2A. 3 / 3
| 3

reach
"All these results suggested that Cezanne might promote PIK3C2A transcription, but not protein stability.As we did not find any report that Cezanne could serve as a transcriptional factor (TF) or co-activator, we tried to identify the mediator between Cezanne and PIK3C2A."

reach
"All these indicated that Cezanne could induce PIK3C2A expression by stabilizing PLOR2A."

reach
"All these results suggested that Cezanne could act as a deubiquitination enzyme to deubiquitinate K48-linked ubiquitination and stabilize POLR2A, then promote the transcription of PIK3C2A in a POLR2A-dependent way.In our study, Cezanne colocalized with PIK3C3 and stabilized PIK3C3 by slowing down its ubiquitin-proteasome pathway degradation (Fig. 3), and we also found Cezanne promoted PIK3C2A transcription (Fig. 5)."
OTUD7B affects MTOR
| 3
OTUD7B activates MTOR. 3 / 3
| 3

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"Overall, our results suggest that OTUD7B knockdown reduces autophagy by activating AKT/mTOR signaling in PC3 cells."

reach
"To identify the underlying mechanism, we speculated that OTUD7B knockdown inhibits autophagy via the AKT/mTOR signaling pathway in PCa cells."

reach
"We found that Cezanne overexpression in NRCMs activated AKT/mTOR to reduce apoptosis, autophagy and oxidative stress; this mechanism of Cezanne was also verified in animal experiments."
OTUD7B affects MMP9
| 3
| 3

sparser
"Moreover, Cezanne was negatively associated with MMP-9 among 230 HCC samples."

sparser
"Therefore, we also assessed the association of Cezanne with MMP-9 protein and investigated the prognostic value of Cezanne combined with serum AFP level in HCC patients."

sparser
"The results showed that Cezanne was negatively associated with MMP-9 in 230 HCC samples ( r  = −0.377, P  < 0.001, Figure  xref b)."
OTUD7B affects GβL
| 3
OTUD7B deubiquitinates GβL.
| 2
OTUD7B leads to the deubiquitination of GβL. 2 / 2
| 2

reach
"For example, OTUD7B activates mTORC2 by deubiquitinating and removing polyubiquitin chains from GβL, promoting its interaction with SIN1, which enhances AKT signaling and thereby contributes to lung tumorigenesis [12]."

reach
"7Bi treatment in NSCLC and HEK293 cells efficiently reduced Akt-pS473 signals by interfering with OTUD7B-directed GβL deubiquitination, leading to reduced cell growth."
OTUD7B decreases the amount of GβL.
| 1
OTUD7B decreases the amount of GβL. 1 / 1
| 1

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"Wang et al. [17] demonstrated that OTU deubiquitinase 7B (OTUD7B) reduced ubiquitination level of GβL to prevent GβL from interacting with SIN1, leading to activation of mTORC2/AKT signaling pathway and down-regulation of mTORC1 expression."
OTUD7B affects Death
| 3
OTUD7B inhibits Death. 3 / 3
| 3

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"OTUD7b prevents DC death in human monocyte-derived DCs."

reach
"DC-specific OTUD7b prevents DC death and protects mice from ECM."

reach
"Taken together, DC-specific OTUD7b inhibits death of DCs and fosters IL-12 production of DCs during PbA infection, which leads to effective priming and intracerebral accumulation of pathogen-specific CD8 T cells leading to disruption of the BBB and development of ECM."

reach
"Consistently, the loss of Otud7b inhibited the activation of three major downstream transcription factors involved in T cell activation, NF-kappaB, NF-AT, and AP1 (XREF_FIG)."

reach
"USP39 suppressed the transcription activity of ETS2 by approximately 72.8%, while OTUD7A and OTUD7B increased the transcription activity of ETS2 by approximately 55.2% and 68.5%, respectively."

reach
"Surprisingly, as a compensatory mechanism of PI3P generation, PIK3C2A was shown to be upregulated by Cezanne by promoting its transcription in a POLR2A-dependent way."
OTUD7B affects CTNNB1
1 1 | 1
OTUD7B binds CTNNB1.
1 | 1
1 | 1

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sparser
"While OTUD7B interacted with β-catenin, it did not deubiquitinate β-catenin [ xref ]."
OTUD7B deubiquitinates CTNNB1.
1 |
OTUD7B deubiquitinates CTNNB1. 1 / 1
1 |

"RNA-sequencing and biochemical studies showed that <span class="match term0">Cezanne</span> drives VSMC proliferation by regulating CCN family member 1 (CCN1) by targeting <span class="match term1">BETA-CATENIN</span> for deubiquitination"
OTUD7B affects CD4
| 3
OTUD7B activates CD4. 3 / 3
| 3

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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."

reach
"In this regard, T cells are essential to eradicate L. monocytogenes from the infected host, and T cell intrinsic expression of OTUD7B augments the protective Listeria -specific CD4 and CD8 T cell resp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"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)."
OTUD7B affects CCNB1
3 |
3 |

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OTUD7B affects C4B_2
| 3
OTUD7B inhibits C4B_2. 3 / 3
| 3

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"Phenylephrine‐induced CH potentiated by OTUD7B knockdown was completely blocked by the upregulation of KLF4 activity."

reach
"Notably, OTUD7B suppressed CH progression by activating AKT signaling cascades and regulating KLF4 (Krüppel‐like factor 4) degradation."

reach
"Similarly, we observed that OTUD7B overexpression attenuated TAC‐induced CH in gain‐of‐function studies."
NFkappaB affects OTUD7B
| 2
NFkappaB activates OTUD7B.
| 1
| 1

reach
"Furthermore, inhibition of NF-kappaB attenuated cone photoreceptor degeneration in the light-exposed Otud7b -/- retina and stress-induced neuronal cell death resulting from Otud7b deficiency."
NFkappaB increases the amount of OTUD7B.
| 1
NFkappaB increases the amount of OTUD7B. 1 / 1
| 1

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"We also found that Otud7b expression was induced by the noncanonical NF-kappaB signals (XREF_SUPPLEMENTARY), indicating a negative-feedback function."
N4BP1 affects OTUD7B
1 | 1 1
N4BP1 binds OTUD7B.
1 | 1
1 | 1

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sparser
"Besides this, N4BP1 interacts with the deubiquitinase (DUB) Cezanne-1, which functions in the deubiquitination and stabilization of TRAF3 [ xref ] and subsequently modulates the activation of both the canonical [ xref ] and non-canonical NFkB [ xref ] by affecting the degradation of NIK and IkB, and the induction of c-REL ubiquitination and proteasome-mediated degradation [ xref ]."
N4BP1 deubiquitinates OTUD7B.
| 1
N4BP1 deubiquitinates OTUD7B. 1 / 1
| 1

reach
"The study of Spel et al. has demonstrated that N4BP1 interacts with deubiquitinating enzyme CEZANNE to inhibit both canonical and noncanonical NF-κB, and then affects immunoregulation of neuroblastoma[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
MMP9 affects OTUD7B
| 3
| 3

sparser
"Moreover, Cezanne was negatively associated with MMP-9 among 230 HCC samples."

sparser
"Therefore, we also assessed the association of Cezanne with MMP-9 protein and investigated the prognostic value of Cezanne combined with serum AFP level in HCC patients."

sparser
"The results showed that Cezanne was negatively associated with MMP-9 in 230 HCC samples ( r  = −0.377, P  < 0.001, Figure  xref b)."
MAP3K14 affects OTUD7B
2 | 1
2 | 1

No evidence text available

sparser
"OTUD7B did not bind to NIK directly, but it did bind to TRAF3 (Fig.  xref a, b)."

No evidence text available
IGF1R affects OTUD7B
2 | 1
2 | 1

sparser
"Methods: Co-Immunoprecipitation assay was performed to investigate the interactions between Cezanne and IGF-1R. A xenograft model was established to assess the efficacy of Cezanne on cancer progression in vivo."

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HIF1 affects OTUD7B
| 3
HIF1 hydroxylates OTUD7B.
| 2
HIF1 hydroxylates OTUD7B. 2 / 2
| 2

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"Finally, the DUB Cezanne (OTUD7B) is hydroxylated by the asparaginyl β-hydroxylase factor inhibiting HIF1 (FIH1) within a domain similar to the Ub-associated domain, and this modification blocks Ub-binding, although the significance of this event remains unknown (172)."

reach
"For instance, hydroxylation of the UBA domain of OTUD7B (Cezanne) by factor inhibiting HIF1 (FIH1) prevents binding to Ub ( Mader et al., 2020 )."
HIF1 increases the amount of OTUD7B.
| 1
HIF1 increases the amount of OTUD7B. 1 / 1
| 1

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"Activation of HIF1α in response to dimethyloxallyl glycine, desferrioxamine or CoCl did not influence Cezanne expression (Online Fig. III) and silencing of HIF1α or HIF2α did not suppress Cezanne expression in hypoxic EC (Online Fig. IV), indicating that induction of Cezanne by hypoxia is HIF-independent."
FOXO4 affects OTUD7B
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FOXO4 decreases the amount of OTUD7B. 3 / 3
3 |

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CCNB1 affects OTUD7B
3 |
3 |

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Vasotocin affects OTUD7B
| 1 1
| 1 1

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"XREF_FIG d, AVT also decreases Otud4, Otud5 and Otud7b in addition to Otub1 and c-Maf."

eidos
"As shown in Fig. 5d , AVT also decreases Otud4 , Otud5 and Otud7b in addition to Otub1 / c-Maf ."
Rotenone affects OTUD7B
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Rotenone decreases the amount of OTUD7B. 2 / 2
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| 2
Retinoic acid increases the amount of OTUD7B. 2 / 2
| 2

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"Others have shown retinoic acid (RA) treatment increases OTUD7B levels in HCC 24 while we observed that OTUD7B was subject to transcriptional repression by p53: the latter finding further suggests that p53 establishes negative feedback towards tuning the cellular levels of OTUD7B."

reach
"Others have shown retinoic acid (RA) treatment increases OTUD7B levels in HCC 24 while we observed that OTUD7B was subject to transcriptional repression by p53: the latter finding further suggests that p53 establishes negative feedback towards tuning the cellular levels of OTUD7B."
Phenylmercury acetate increases the amount of OTUD7B. 2 / 2
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MiR-1180 affects OTUD7B
| 2
MiR-1180 inhibits OTUD7B. 2 / 2
| 2

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"In summary, the present study demonstrates that the upregulation of miR-1180 contributes to the proliferation and cisplatin-resistance of HCC cells both in vitro and in vivo, by targeting and suppressing OTUD7B, TNIP2 and BAD."

reach
"Moreover, we reveal that the miR-1180 directly targets two negative regulators of the nuclear factor (NF)-kappaB signaling pathway (OTUD7B and TNIP2) XREF_BIBR XREF_BIBR XREF_BIBR, as well as the pro apoptotic Bcl-2 associated death promoter (BAD) protein, via post-transcriptional downregulation."
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Hsa-mir-4533 decreases the amount of OTUD7B. 2 / 2
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Hsa-mir-4516 decreases the amount of OTUD7B. 2 / 2
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Hsa-mir-4475 decreases the amount of OTUD7B. 2 / 2
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Hsa-mir-4434 decreases 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-6134 decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-6079 decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-5703 decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-4799-5p decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-154-5p decreases the amount of OTUD7B. 2 / 2
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Hsa-miR-103a-3p decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
Entinostat affects OTUD7B
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Entinostat decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
Dioxygen affects OTUD7B
| 1
| 1

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"The DUB Cezanne and OTUD7B is itself induced by oxygen deprivation in cultured endothelial cells."
Cadmium dichloride increases the amount of OTUD7B. 2 / 2
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No evidence text available

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

No evidence text available
All-trans-retinoic acid increases the amount of OTUD7B. 2 / 2
1 | 1

No evidence text available

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"Conversely, ATRA treatment has been reported to increase the expression of the OTUD7B gene, an NF-κB inhibitory factor [49], indicating that inflammatory cell death, as observed with GGA or PA treatment, is unlikely to occur."
ZEB1 affects OTUD7B
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ZEB1 decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
WWP2 affects OTUD7B
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No evidence text available

No evidence text available
VEGFA affects OTUD7B
| 2
| 2

sparser
"Immunoprecipitation was used to confirm the interaction between OTU deubiquitinase 7B (OTUD7B) and vascular endothelial growth factor A (VEGFA), and the level of ubiquitinated VEGFA."

sparser
"Further exploration revealed that OTUD7B interacts with VEGFA and that the miR-491-5p-OTUD7B axis modulates the ubiquitination of VEGFA."
UBE2S affects OTUD7B
1 | 1
UBE2S inhibits OTUD7B.
| 1
UBE2S inhibits OTUD7B. 1 / 1
| 1

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"In favor of this hypothesis, codepletion of UBE2S rescued the phenotypes of Cezanne knockdown cells: (1) the formation of BRCA1-A foci, (2) the cell's ability to repair DNA lesions (assayed by the disappearance of γH2A.X foci over time), and (3) IR sensitivity."
UBE2S binds OTUD7B.
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No evidence text available
UBD affects OTUD7B
| 2
| 2

sparser
"When aligning trajectories of the Cezanne-1 K11-linked diubiquitin complex to those of Cezanne-1, the relative RMSD (rRMSD) gives information about conformational transitions and differences in translational and rotational motions of the ubiquitins."

sparser
"To investigate the native diubiquitin Cezanne-1 complex, the physiological DIST-Gly75-Gly76-Lys11-PRO iso-peptide linkage was reconstituted."
TFDP2 affects OTUD7B
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TFDP2 decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
Sal-miR-1 and 3 affects OTUD7B
| 2
Sal-miR-1 and 3 decreases the amount of OTUD7B. 2 / 2
| 2

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"The results showed that stimulation of human VSMCs with thrombin could reduce NMHC IIA expression and enhance the expression of OTUD7B and KLF4, which could be largely reversed by transfecting Sal-miR-1 and 3 (XREF_SUPPLEMENTARY D)."

reach
"Together, these data indicate that Sal-miR-1 and 3 negatively regulate OTUD7B expression via directly targeting the 3 ' UTR of OTUD7B mRNA."
SOX9 affects OTUD7B
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SOX9 decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
SOX2 affects CREBZF
| 2
| 2

sparser
"To further confirm the direct binding of Sox2 to OTUD7B ZF domain, we purified recombinant GST-tagged OTUD7B truncates, including GST-OTUD7B-N (1-359), GST-OTUD7B-C (360–843), GST-OTUD7B-△ZF (1–810), and GST-OTUD7B-ZF (811–843) (Fig.  xref )."

sparser
"The result of GST pull-down assay indicated that Sox2 interacted with OTUD7B ZF domain directly in cell-free system (Fig.  xref )."
RIPK1 affects OTUD7B
| 1 1
RIPK1 binds OTUD7B.
| 1
| 1

sparser
"TNF stimulation also resulted in an interaction between TRAF2-RIPK1 and RIPK1-OTUD7b (Fig. xref )."
RIPK1 activates OTUD7B.
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RIPK1 activates OTUD7B. 1 / 1
| 1

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"However, combined pharmacological inhibition of RIPK1 activity (Nec1s) and apoptosis (zVAD-FMK) completely rescued survival of OTUD7b-deficient BMDC in vitro and in vivo indicating that OTUD7b inhibits RIPK1-independent and to a lesser extent RIPK1-dependent DC apoptosis [43]."
RHBDL2 affects OTUD7B
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No evidence text available

No evidence text available
PIK3R3 affects OTUD7B
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No evidence text available

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

No evidence text available
| 2
| 2

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"As a result, we hypothesized that OTUD7B promotes Wnt signaling by facilitating the nuclear localization of LEF1 and/or its interaction with β-catenin within the nucleus."

reach
"Furthermore, OTUD7B promotes the nuclear localization of LEF1, leading to an increased interaction with beta-catenin in the nucleus while not noticeably affecting ubiquitination on LEF1."
| 2

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"The results described above prompted us to examine whether Otud7b negatively regulates mucosal immunity against infections."

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"Collectively, these findings suggest the intriguing possibility that inhibition of Otud7b may enhance mucosal immunity against C. rodentium infection."
| 2

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"In ERα-negative breast cancer, silencing OTUD7B inhibits cell migration and invasion in vitro and impairs lung metastasis of cancer cells in vivo by increasing lysine-specific demethylase 1 (LSD1)-Ub and targeting LSD1 for p62-mediated proteolysis (16)."

reach
"OTUD7B promotes cell migration and invasion, predicting poor prognosis of gastric cancer."
OTUD7B affects activation
| 2
OTUD7B inhibits activation. 2 / 2
| 2

sparser
"Because K11-linked polyubiquitin chains have been identified in the activated TNFR1 complex, these results imply that Cezanne may inhibit TNF-induced NF-κB activation by hydrolyzing K11-linked polyubiquitin chains on substrates present in the TNFR1 complex."

sparser
"In this current issue, Luong et al. report that Cezanne can also inhibit NF-κB-dependent inflammatory activation in response to hypoxia-reoxygenation by reducing TRAF6 K63 polyubiquitination."

eidos
"OTUD7B Activates Wnt Signaling Pathway through the Interaction with LEF1 ."

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"OTUD7B Activates Wnt Signaling Pathway through the Interaction with LEF1."
OTUD7B affects WWP2
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No evidence text available

No evidence text available

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"Cardiomyocyte-specific knockdown of OTUD7B exacerbates pressure overload-induced ventricular remodeling."

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"These results indicate that the ferroptosis inhibitor Fer-1 and HNF4α overexpression can rescue adverse ventricular remodeling caused by OTUD7B knockdown."
OTUD7B affects VEGFA
| 2
| 2

sparser
"Immunoprecipitation was used to confirm the interaction between OTU deubiquitinase 7B (OTUD7B) and vascular endothelial growth factor A (VEGFA), and the level of ubiquitinated VEGFA."

sparser
"Further exploration revealed that OTUD7B interacts with VEGFA and that the miR-491-5p-OTUD7B axis modulates the ubiquitination of VEGFA."
OTUD7B affects VEGF
| 2
OTUD7B activates VEGF. 2 / 2
| 2

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"ELISA and tube formation assay revealed OTUD7B promotes VEGF production and angiogenesis."

reach
"Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT and VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma."
OTUD7B affects UIMC1
| 2
OTUD7B activates UIMC1. 2 / 2
| 2

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"Whereas the UBA domain by itself does not rescue RAP80, Abraxas, and BRCA1 IRIF, a truncated N terminus of Cezanne that contains both the UBA domain and the DUB domain (UBA-OTU), but not a DUB inactivated version (UBA-OUT*), rescues the phenotype (Fig. 3B)."

reach
"The different roles of Cezanne and Cezanne2 in promoting Rap80 or Rad18 and 53BP1 suggest that the K63-dependent recruitments of DNA repair proteins are differentially regulated by Cezanne and Cezanne2."
OTUD7B affects UBD
| 2
| 2

sparser
"When aligning trajectories of the Cezanne-1 K11-linked diubiquitin complex to those of Cezanne-1, the relative RMSD (rRMSD) gives information about conformational transitions and differences in translational and rotational motions of the ubiquitins."

sparser
"To investigate the native diubiquitin Cezanne-1 complex, the physiological DIST-Gly75-Gly76-Lys11-PRO iso-peptide linkage was reconstituted."
OTUD7B affects TCR
| 1 1
OTUD7B inhibits TCR. 2 / 2
| 1 1

sparser
"In T cells, OTUD7B inhibits TCR and CD28-mediated activation by regulating the non-degradative ubiquitination of ZAP70, a central molecule in proximal TCR signaling xref ."

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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 affects Sal-miR-1
| 2
OTUD7B activates Sal-miR-1. 2 / 2
| 2

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"Reversely, OTUD7B overexpression mediated by pcDNA3.1-OTUD7B partially blocked Sal-miR-1 and 3 inhibition of VSMC migration."

reach
"To further confirm whether OTUD7B is a direct target of Sal-miR-1 and 3, we co-transfected cells with Sal-miR-1 or Sal-miR-3 alone or together, both of which bind to the different sites on OTUD7B 3 ' UTR, along with OTUD7B 3 ' UTR- or its mutant (OTUD7B-MUT)-mediated luciferase reporter."
OTUD7B affects SIRT6
| 1 1
OTUD7B decreases the amount of SIRT6.
| 1
OTUD7B decreases the amount of SIRT6. 1 / 1
| 1

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"The inhibition of Cezanne increased SIRT6 levels and conferred neuroprotection after cerebral ischemia injury in rats and in cultured neurons after OGD insult [45]."
OTUD7B activates SIRT6.
| 1
OTUD7B activates SIRT6. 1 / 1
| 1

eidos
"Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons ."
OTUD7B affects RHBDL2
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No evidence text available

No evidence text available
OTUD7B affects Proteasome
| 1
| 1

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"Notably, in the presence of MG132, the protein level of HNF4α was not affected by OTUD7B, suggesting that OTUD7B inhibits HNF4α degradation via ubiquitin–proteasome system."

reach
"However, the mechanism deubiquitinating enzyme OTUD7B promoted PC progress is not clear."

reach
"The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137."
OTUD7B affects PIK3R3
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No evidence text available

No evidence text available
OTUD7B affects OLR1
| 2
OTUD7B increases the amount of OLR1.
| 1
OTUD7B increases the amount of OLR1. 1 / 1
| 1

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"Knockdown of OTUD7B significantly reduced the level of Lox-1 and impaired the uptake of oxLDL by these cells."
OTUD7B decreases the amount of OLR1.
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OTUD7B decreases the amount of OLR1. 1 / 1
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"Importantly, overexpression of Lox-1 effectively rescued oxLDL uptake by OTUD7B-deficient THP-1 and U937 cells."
OTUD7B affects NUAK2
| 2
OTUD7B increases the amount of NUAK2. 2 / 2
| 2

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"Meanwhile, OTUD7B can accelerate gastric cancer procession through upregulating NUAK2 expression [11]."

reach
"OTUD7B deubiquitinates and stabilizes YAP1 to upregulate NUAK2 expression, thus accelerating gastric cancer procession."
OTUD7B affects NR4A2
| 1 1
| 1 1

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"NR4A2 ChIP-seq and RNA-seq data excluded transcriptional regulation of NR4A2 to OTUD7B, and it was experimentally evidenced that NR4A2 bound to OTUD7B promoter region and positively transcriptionally regulate OTUD7B expression."

sparser
"NR4A2 ChIP-seq and RNA-seq data excluded transcriptional regulation of NR4A2 to OTUD7B, and it was experimentally evidenced that NR4A2 bound to OTUD7B promoter region and positively transcriptionally regulate OTUD7B expression."
OTUD7B affects NOTCH1
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No evidence text available

No evidence text available
OTUD7B affects NMHC IIA
| 2
OTUD7B inhibits NMHC IIA. 2 / 2
| 2

eidos
"Together , these findings indicated that Sal-miR1 +3 enhance the expression levels of NMHC IIA gene by suppressing OTUD7B expression and thus reducing KLF4 protein levels ."

eidos
"Remarkably , Sal-miR-1 and 3 increased the expression levels of NMHC IIA by inhibiting OTUD7B expression and thus reducing KLF4 protein levels ."
OTUD7B affects N4BP1
1 | 1
1 | 1

No evidence text available

sparser
"Besides this, N4BP1 interacts with the deubiquitinase (DUB) Cezanne-1, which functions in the deubiquitination and stabilization of TRAF3 [ xref ] and subsequently modulates the activation of both the canonical [ xref ] and non-canonical NFkB [ xref ] by affecting the degradation of NIK and IkB, and the induction of c-REL ubiquitination and proteasome-mediated degradation [ xref ]."
OTUD7B affects MYH7
| 2
OTUD7B decreases the amount of MYH7. 2 / 2
| 2

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"Furthermore, OTUD7B knockdown led to elevated mRNA levels of Bnp, Myh7, and Col3a1, along with increased BNP and COL3A1 protein expression, effects that were reversed upon OTUD7B overexpression."

reach
"However, OTUD7B overexpression significantly reduced cardiomyocyte hypertrophy and downregulated the mRNA expressions of NPPA, NPPB, Myh7, and Acta1 compared with those in the AdVector phenylephrine control group (Figure 4E and 4F)."
OTUD7B affects MYC
1 | 1
1 | 1

sparser
"MycOTUD7B and Myc‐LSD1 were generated by subcloning the corresponding cDNAs into the pCDNA3.1‐Myc expressing vector via BamHI and XhoI sites."

No evidence text available
OTUD7B affects LCL161-induced lung cancer cell invasion
| 2
OTUD7B inhibits LCL161-induced lung cancer cell invasion. 2 / 2
| 2

eidos
"Furthermore , OTUD7B can inhibit LCL161-induced lung cancer cell invasion and migration by deubiquitinating TRAF3 , inhibiting NIK and preventing non-canonical NF-kappaB activation ."

eidos
"Consistently , OTUD7B ( WT ) but not OTUD7B ( CH ) inhibited activation of the non-canonical NF-kappaB pathway and LCL161-induced lung cancer cell invasion and migration ( Fig. 9 ) ."
OTUD7B affects LCL161-induced lung cancer cell intrapulmonary metastasis
| 2
OTUD7B inhibits LCL161-induced lung cancer cell intrapulmonary metastasis. 2 / 2
| 2

eidos
"Finally , we investigated whether OTUD7B inhibits LCL161-induced lung cancer cell intrapulmonary metastasis in vivo , and our analysis of clinical samples was consistent with the above findings ."

eidos
"OTUD7B inhibits LCL161-induced lung cancer cell intrapulmonary metastasis in vivo ."
OTUD7B affects LCL161-induced invasion
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OTUD7B inhibits LCL161-induced invasion. 2 / 2
| 2

eidos
"Moreover , OTUD7B inhibits LCL161-induced invasion and migration by binding to and deubiquitinating TRAF3 , thereby inhibiting NIK and preventing non-canonical NF-kappaB activation ."

eidos
"However , whether OTUD7B can inhibit LCL161-induced invasion and migration and be used to select a target population in LCL161 treatment for lung cancer is unclear ."
OTUD7B affects KRAS
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OTUD7B activates KRAS. 2 / 2
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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."

reach
"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."
OTUD7B affects K11
| 2
| 2

sparser
"A K11 diUb probe was used to react with Cezanne to form a Cezanne-K11 diUb complex for crystallization."

sparser
"S1–S1′ diUb ABPs have also successfully trapped and allowed the crystallization of the Cezanne-K11 diUb complex ( xref ) and the OTULIN-Met1 diUb complex ( xref )."
OTUD7B affects HSFY2
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No evidence text available

No evidence text available
OTUD7B affects HIF1
| 2
OTUD7B increases the amount of HIF1.
| 1
OTUD7B increases the amount of HIF1. 1 / 1
| 1

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"The expression of HIF-1α is mediated by the dual mechanisms of transcriptional activation by NF-κB and stabilization by the deubiquitinating enzyme Cezanne."
OTUD7B hydroxylates HIF1.
| 1
OTUD7B leads to the hydroxylation of HIF1. 1 / 1
| 1

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"Thereby, the OTUD7B action towards HIF-1α interferes with VHL, but not with PHD-mediated HIF-1α hydroxylation."
OTUD7B affects H3K4me2
| 2
OTUD7B activates H3K4me2. 2 / 2
| 2

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"The fact that many of these gene hits are linked to cell cycle likely explains the result that the primary functions of OTUD7B or LSD1 in coordinating cell cycle progression.The above ChIP‐seq and RNA‐seq datasets were aligned to explore the potential correlations between OTUD7B‐induced H3K4me2 and LSD1 occupancy changes and changes in gene transcription."

reach
"Importantly, in LSD1‐reconstituted cells, LSD1 rendered their promoters resistant to OTUD7B ablation‐induced H3K4me2/H3K9me2 alterations (Figure 6J,L)."
OTUD7B affects FlaG
| 2
| 2

sparser
"HA-HIF-1α co-immunoprecipitated with FLAG-OTUD7B, while the reciprocal Co-IP also confirmed the association of HIF-1α with OTUD7B. These findings definitively established the interaction between OTUD7B and HIF-1α ( xref )."

sparser
"To confirm this interaction, HA-HIF-1α and FLAG-OTUD7B were ectopically expressed in TE-8 cells and the cell lysate was subjected to IP using anti-FLAG/HA antibody."
OTUD7B affects FZR1
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No evidence text available

No evidence text available
OTUD7B affects FAO genes
| 2
OTUD7B increases the amount of FAO genes. 2 / 2
| 2

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"qRT-PCR showed that OTUD7B knockdown significantly downregulated the expression of FAO genes (Acot1, Cd36, Cpt2, Crat, Cpt1b, and Acadm) after PE stimulation (Fig. 6B)."

reach
"In contrast, overexpression of OTUD7B led to an increase in HNF4α and ACOT1 expression (Fig. 6C), and significantly upregulated the transcription of FAO genes (Acot1, Cd36, Cpt2, Crat, Cpt1b, and Acadm) after PE stimulation (Fig. 6D)."
OTUD7B affects Disease
| 2
| 2

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"The evidence suggests that there was a strong correlation between the release of CA125 and IFN-γ in psoriatic patients.Since A20, CYLD and Cezanne negatively regulate the inflammatory response in autoimmune and cancer diseases, their mRNA levels were examined by quantitative real-time PCR."

reach
"The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases."
OTUD7B affects CREBZF
| 2
| 2

sparser
"To further confirm the direct binding of Sox2 to OTUD7B ZF domain, we purified recombinant GST-tagged OTUD7B truncates, including GST-OTUD7B-N (1-359), GST-OTUD7B-C (360–843), GST-OTUD7B-△ZF (1–810), and GST-OTUD7B-ZF (811–843) (Fig.  xref )."

sparser
"The result of GST pull-down assay indicated that Sox2 interacted with OTUD7B ZF domain directly in cell-free system (Fig.  xref )."
OTUD7B affects CDC20
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No evidence text available

No evidence text available
OTUD7B affects CD8
| 2
OTUD7B activates CD8. 2 / 2
| 2

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"In this regard, T cells are essential to eradicate L. monocytogenes from the infected host, and T cell intrinsic expression of OTUD7B augments the protective Listeria -specific CD4 and CD8 T cell resp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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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)."
OTUD7B affects BECN1
1 | 1
1 | 1

No evidence text available

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"CO-IP assay showed that Cezanne could bind PIK3C3 rather than Beclin-1 (Fig. 3B, C)."
OTUD7B affects Akt-pS473
| 2
OTUD7B activates Akt-pS473. 2 / 2
| 2

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"More importantly, pharmacological inhibition of OTUD7B by 7Bi reduced Akt-pS473 signals in HL60 (Figure 4H), K562 (Figure 4I) and THP1 (Figure 4J) cells, mimicking the effects of OTUD7B depletion."

reach
"Furthermore, we report in leukemia cells, either genetic depletion or 7Bi-mediated pharmacological inhibition of OTUD7B reduces Akt-pS473 via inhibiting the OTUD7B/GbetaL signaling axis."
OTUD7B affects ATG7
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OTUD7B increases the amount of ATG7. 2 / 2
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"In addition, OTUD7B knockdown significantly decreased levels of the autophagosome formation markers VPS34, ATG14L, and ATG7 and significantly increased p62."

reach
"As shown in Fig. 3A, our results showed that OTUD7B knockdown significantly decreased the levels of VPS34, ATG14L, p-Becline1, ATG7, and LC3B-II/I, while levels of P62 were significantly increased compared with the negative control cell."
OTUD7B affects APC_C
| 2
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sparser
"Accordingly, Cezanne binds established APC/C substrates and reverses their APC/C-mediated ubiquitination."

sparser
"Cezanne binds APC/C substrates, reverses their ubiquitination and protects them from degradation."
OTUD7B affects ACSL4
| 2
OTUD7B increases the amount of ACSL4.
| 1
OTUD7B increases the amount of ACSL4. 1 / 1
| 1

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"In vitro, OTUD7B knockdown yielded similar results, marked by decreased SOD activity, reduced GSH levels, increased MDA content, elevated ACSL4 protein expression, and reduced xCT and GPX4 protein expression (Fig. 4C, D, E, G)."
OTUD7B decreases the amount of ACSL4.
| 1
OTUD7B decreases the amount of ACSL4. 1 / 1
| 1

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"In vitro, OTUD7B knockdown yielded similar results, marked by decreased SOD activity, reduced GSH levels, increased MDA content, elevated ACSL4 protein expression, and reduced xCT and GPX4 protein expression (Fig. 4C, D, E, G)."
NR4A2 affects OTUD7B
| 1 1
| 1 1

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"NR4A2 ChIP-seq and RNA-seq data excluded transcriptional regulation of NR4A2 to OTUD7B, and it was experimentally evidenced that NR4A2 bound to OTUD7B promoter region and positively transcriptionally regulate OTUD7B expression."

sparser
"NR4A2 ChIP-seq and RNA-seq data excluded transcriptional regulation of NR4A2 to OTUD7B, and it was experimentally evidenced that NR4A2 bound to OTUD7B promoter region and positively transcriptionally regulate OTUD7B expression."
NOTCH1 affects OTUD7B
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No evidence text available

No evidence text available
MYC affects OTUD7B
1 | 1
1 | 1

sparser
"MycOTUD7B and Myc‐LSD1 were generated by subcloning the corresponding cDNAs into the pCDNA3.1‐Myc expressing vector via BamHI and XhoI sites."

No evidence text available
MIR658 affects OTUD7B
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MIR658 decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
MIR107 affects OTUD7B
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MIR107 decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
MAZ affects OTUD7B
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MAZ decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
K11 affects OTUD7B
| 2
| 2

sparser
"A K11 diUb probe was used to react with Cezanne to form a Cezanne-K11 diUb complex for crystallization."

sparser
"S1–S1′ diUb ABPs have also successfully trapped and allowed the crystallization of the Cezanne-K11 diUb complex ( xref ) and the OTULIN-Met1 diUb complex ( xref )."
IL1 affects OTUD7B
| 2
IL1 activates OTUD7B. 2 / 2
| 2

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"Given that Cezanne can be modulated by shear stress, TNFα, IL-1 and reactive oxygen species , future studies should address whether these factors influence inflammatory responses to hypoxia-reoxygenation by altering the expression and/or activity of Cezanne."

reach
"Our subsequent studies revealed that Cezanne can be induced by TNFα, IL-1 and functions as an inhibitor of NF-κB, thus forming a negative feedback loop in inflammatory cytokine signalling , and a recent report indicated that Cezanne can also influence non-canonical NF-κB activation ."
HSFY2 affects OTUD7B
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2 |

No evidence text available

No evidence text available
FlaG affects OTUD7B
| 2
| 2

sparser
"HA-HIF-1α co-immunoprecipitated with FLAG-OTUD7B, while the reciprocal Co-IP also confirmed the association of HIF-1α with OTUD7B. These findings definitively established the interaction between OTUD7B and HIF-1α ( xref )."

sparser
"To confirm this interaction, HA-HIF-1α and FLAG-OTUD7B were ectopically expressed in TE-8 cells and the cell lysate was subjected to IP using anti-FLAG/HA antibody."
FZR1 affects OTUD7B
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No evidence text available

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

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

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

No evidence text available
Cuprizon affects OTUD7B
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Cuprizon decreases the amount of OTUD7B. 2 / 2
2 |

No evidence text available

No evidence text available
CTNNB1 affects OTUD7B
1 | 1
1 | 1

No evidence text available

sparser
"While OTUD7B interacted with β-catenin, it did not deubiquitinate β-catenin [ xref ]."
CREBZF affects SOX2
| 2
| 2

sparser
"To further confirm the direct binding of Sox2 to OTUD7B ZF domain, we purified recombinant GST-tagged OTUD7B truncates, including GST-OTUD7B-N (1-359), GST-OTUD7B-C (360–843), GST-OTUD7B-△ZF (1–810), and GST-OTUD7B-ZF (811–843) (Fig.  xref )."

sparser
"The result of GST pull-down assay indicated that Sox2 interacted with OTUD7B ZF domain directly in cell-free system (Fig.  xref )."
CDC20 affects OTUD7B
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2 |

No evidence text available

No evidence text available
BECN1 affects OTUD7B
1 | 1
1 | 1

No evidence text available

reach
"CO-IP assay showed that Cezanne could bind PIK3C3 rather than Beclin-1 (Fig. 3B, C)."
APC_C affects OTUD7B
| 2
| 2

sparser
"Accordingly, Cezanne binds established APC/C substrates and reverses their APC/C-mediated ubiquitination."

sparser
"Cezanne binds APC/C substrates, reverses their ubiquitination and protects them from degradation."
6-propyl-2-thiouracil decreases the amount of OTUD7B. 2 / 2
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No evidence text available

No evidence text available
VIRF-2 affects OTUD7B
| 1
VIRF-2 ubiquitinates OTUD7B. 1 / 1
| 1

sparser
"Multiple DUBs from the human ovarian tumor (OTU) DUB family that display various degrees of specificities towards different ubiquitin linkage types have been identified and can be used for UbiCRest: For instance, OTUB1 specifically cleaves K48-, OTUD1 K63-, Cezanne K11-, and OTULIN M1-linked ubiquitylation, whereas OTUD3 displays specificity towards K6- and K11-linked ubiquitylation ( xref )."
Thiram affects OTUD7B
1 |
Thiram increases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Sulfadimethoxine decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Sodium arsenite increases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
Saxitoxin affects OTUD7B
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Saxitoxin increases the amount of OTUD7B. 1 / 1
1 |

No evidence text available

reach
"Given that Cezanne can be modulated by shear stress, TNFα, IL-1 and reactive oxygen species , future studies should address whether these factors influence inflammatory responses to hypoxia-reoxygenation by altering the expression and/or activity of Cezanne."
1 |
Pyrimidifen decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Pyrachlostrobin decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |

No evidence text available
1 |
Pirinixic acid increases the amount of OTUD7B. 1 / 1
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No evidence text available
PcDNA3.1-OTUD7B affects OTUD7B
| 1
PcDNA3.1-OTUD7B decreases the amount of OTUD7B. 1 / 1
| 1

reach
"Reversely, OTUD7B overexpression mediated by pcDNA3.1-OTUD7B partially blocked Sal-miR-1 and 3 inhibition of VSMC migration."
Parathion affects OTUD7B
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Parathion increases the amount of OTUD7B. 1 / 1
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No evidence text available
Monoubiquitin affects OTUD7B
| 1
Monoubiquitin binds OTUD7B. 1 / 1
| 1

reach
"The monoubiquitin-bound OTUD7B crystal structure 5LRW (after removal of the monoubiquitin), which had also served as the homology template for our previous work on OTUD7A, was chosen for the virtual screen, with the binding site located between residues W234, Q237, Q238, T239, Q241, N242, S245, G246, L247, Y249, W254, E257, W258, E260, L261, L264, L294, E295, E296, F297, H298, P330, F331, H390, and F391."
1 |
Midostaurin decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Methimazole decreases the amount of OTUD7B. 1 / 1
1 |

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

No evidence text available
1 |
1 |

No evidence text available
Linc00976 affects OTUD7B
| 1
Linc00976 increases the amount of OTUD7B. 1 / 1
| 1

isi
"The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137."
Inulin affects OTUD7B
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Inulin decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-mir-548s decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-mir-4739 decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4698 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-mir-4663 decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4537 decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4457 decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4284 decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4282 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-92b-3p decreases the amount of OTUD7B. 1 / 1
1 |

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

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

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

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

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

No evidence text available
1 |
Hsa-miR-6851-5p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-6849-3p decreases the amount of OTUD7B. 1 / 1
1 |

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

No evidence text available
1 |
Hsa-miR-6721-5p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-6720-5p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-6516-5p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-6514-3p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6500-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6499-3p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-616-5p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-5189-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-513a-3p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-508-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-500a-3p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4756-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4419b decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-373-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-371b-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3689d decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-367-3p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-363-3p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3606-3p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-339-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3202 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-32-5p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-3190-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-24-3p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-214-5p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-19a-3p decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-1292-3p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
Hsa-miR-125b-2-3p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Hsa-miR-1229-3p decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Fulvestrant demethylates OTUD7B. 1 / 1
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No evidence text available
1 |
Doxorubicin decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Dorsomorphin decreases the amount of OTUD7B. 1 / 1
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No evidence text available
Diethylstilbestrol increases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Deoxynivalenol increases the amount of OTUD7B. 1 / 1
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No evidence text available
Decabromodiphenyl ether increases the amount of OTUD7B. 1 / 1
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No evidence text available
Curcumin affects OTUD7B
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Curcumin decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
Cadmium atom increases the amount of OTUD7B. 1 / 1
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No evidence text available
Butanal affects OTUD7B
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Butanal decreases the amount of OTUD7B. 1 / 1
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No evidence text available
1 |
1 |

No evidence text available
Atrazine affects OTUD7B
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Atrazine increases the amount of OTUD7B. 1 / 1
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No evidence text available
Asparaginyl β-hydroxylase factor affects OTUD7B
| 1
Asparaginyl β-hydroxylase factor hydroxylates OTUD7B. 1 / 1
| 1

reach
"Finally, the DUB Cezanne (OTUD7B) is hydroxylated by the asparaginyl β-hydroxylase factor inhibiting HIF1 (FIH1) within a domain similar to the Ub-associated domain, and this modification blocks Ub-binding, although the significance of this event remains unknown (172)."
Anti-LTbetaR affects OTUD7B
| 1
Anti-LTbetaR activates OTUD7B. 1 / 1
| 1

reach
"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)."
1 |
Aflatoxin B1 increases the amount of OTUD7B. 1 / 1
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No evidence text available
Abrine affects OTUD7B
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Abrine increases the amount of OTUD7B. 1 / 1
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No evidence text available
ZDHHC17 affects OTUD7B
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No evidence text available
WWOX affects OTUD7B
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No evidence text available
VIRMA affects OTUD7B
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No evidence text available
VDR affects OTUD7B
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VDR decreases the amount of OTUD7B. 1 / 1
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No evidence text available
US7 affects OTUD7B
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1 |

No evidence text available
UBA domain affects OTUD7B
| 1
OTUD7B binds K63-, and UBA domain. 1 / 1
| 1

reach
"We confirmed the binding of the UBA domain of Cezanne and Cezanne2 to K63-, but not K48- or K11-tetra-ubiquitin in the in vitro pull-down assay using purified recombinant GST-tagged protein fragments and linkage-specific ubiquitin chains (Fig. 1B)."
TNIP2 affects OTUD7B
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No evidence text available
TNFSF13B affects OTUD7B
| 1
| 1

reach
"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)."
TNFRSF1A affects OTUD7B
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No evidence text available
TNFAIP3 affects OTUD7B
| 1

sparser
"Here, we identified that the A20-mediated dynamic change of RIPK1 ubiquitination, resulted in a shift of the targeted ubiquitin chains of OTUD7B from K63 to K48 of RIPK1, and that OTUD7B interacted with A20 and diminished K48 polyubiquitination of RIPK1."
TNF receptor affects OTUD7B
| 1
OTUD7B binds TNF receptor. 1 / 1
| 1

reach
"Cezanne recruitment to the activated TNF receptor leads to strongly diminished RIP1 polyubiquitylation."
TFAP2C affects OTUD7B
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TFAP2C decreases the amount of OTUD7B. 1 / 1
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No evidence text available
Sirolimus affects OTUD7B
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Sirolimus increases the amount of OTUD7B. 1 / 1
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No evidence text available
Sal-miR1 affects OTUD7B
| 1
Sal-miR1 decreases the amount of OTUD7B. 1 / 1
| 1

reach
"Together, these findings indicated that Sal-miR1 +3 enhance the expression levels of NMHC IIA gene by suppressing OTUD7B expression and thus reducing KLF4 protein levels."
Sal-miR-3 affects OTUD7B
| 1
Sal-miR-3 decreases the amount of OTUD7B. 1 / 1
| 1

reach
"Next, we confirmed that Sal-miR-1 or Sal-miR-3 alone or together significantly inhibited the expression of OTUD7B mRNA and protein, but did not affect KLF3 and KLF10 expression, indicating the specificity of these two miRNA target recognition (XREF_SUPPLEMENTARY B-C)."
SRY affects OTUD7B
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SRY decreases the amount of OTUD7B. 1 / 1
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No evidence text available
SP1 affects OTUD7B
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SP1 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
SHBG affects OTUD7B
| 1
OTUD7B binds DiUb and SHBG. 1 / 1
| 1

sparser
"A detailed analysis of internal K11-linked diUb ABP binding to Cezanne revealed that recognition of S1′ site ubiquitin leads to a large dynamic conformational change and subsequent catalysis in Cezanne."
| PMC
SAXO4 affects OTUD7B
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1 |

No evidence text available

No evidence text available
Rap80/Abraxas/BRCA1 affects OTUD7B
| 1
Rap80/Abraxas/BRCA1 bound to RAD18 inhibits OTUD7B. 1 / 1
| 1

reach
"Thus, Cezanne2 facilitates Cezanne in regulating Rap80/Abraxas/BRCA1 and Rad18 recruitment.Whereas knockdown of either Cezanne or Cezanne2 alone did not result in much change in 53BP1 IRIF (Fig. 7B; Supplemental Fig. S8), depletion of both genes by siRNAs, however, led to a significant decrease in 53BP1 IRIF (Fig. 7B)."
RXRB affects OTUD7B
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RXRB decreases the amount of OTUD7B. 1 / 1
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No evidence text available
RCOR1 affects OTUD7B
| 1
| 1

reach
"Notably, we were unable to detect any significant interaction between OTUD7B and CoREST when both were ectopically expressed, even in cells expressing ectopic LSD1 (Figure S1E, Supporting Information)."
PSMB1 affects OTUD7B
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1 |

No evidence text available
PPARA affects OTUD7B
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PPARA decreases the amount of OTUD7B. 1 / 1
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No evidence text available
POU1F1 affects OTUD7B
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POU1F1 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
PCB138 affects OTUD7B
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PCB138 increases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
PAX5 affects OTUD7B
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PAX5 decreases the amount of OTUD7B. 1 / 1
1 |

No evidence text available
OTUD7B affects signaling
| 1
OTUD7B inhibits signaling. 1 / 1
| 1

sparser
"Together, the data from these studies indicate that Cezanne can inhibit canonical NF-κB signaling through the de-ubiquitination of TRAF6 both in vitro and in vivo ( xref )."
OTUD7B affects required VHL
| 1
OTUD7B activates required VHL. 1 / 1
| 1

eidos
"Further , the effects of OTUD7B on HIF-1alpha were not dependent on PHD-mediated HIF-1alpha hydroxylation , but required VHL ."

reach
"Notably, OTUD7B suppressed CH progression by activating AKT signaling cascades and regulating KLF4 (Krüppel‐like factor 4) degradation."
| 1

reach
"These results indicated that OTUD7B attenuated the phenylephrine‐induced hypertrophic growth of primary cardiomyocytes."
OTUD7B affects p53.Finally
| 1
OTUD7B deubiquitinates p53.Finally. 1 / 1
| 1

reach
"Together these findings establish that OTUD7B functions to de-ubiquitinate wildtype and mutant forms of p53.Finally, to ascertain the type of ubiquitin modification present in p53 removed by OTUD7B, we repeated the ubiquitination assay after transfecting a series of ubiquitin mutants (K6, K11, K27, K29, K33, K48 and K63) where all but one lysine had not been mutated (Figure 4G)."
OTUD7B affects nppb
| 1
OTUD7B decreases the amount of nppb. 1 / 1
| 1

reach
"Furthermore, OTUD7B knockdown led to elevated mRNA levels of Bnp, Myh7, and Col3a1, along with increased BNP and COL3A1 protein expression, effects that were reversed upon OTUD7B overexpression."
OTUD7B affects noncanonical NF-kappaB
| 1
OTUD7B inhibits noncanonical NF-kappaB. 1 / 1
| 1

eidos
"70 OTUD7B deficiency leads to enhanced noncanonical NF-kappaB activity ."
OTUD7B affects monoubiquitin
| 1
Monoubiquitin binds OTUD7B. 1 / 1
| 1

reach
"The monoubiquitin-bound OTUD7B crystal structure 5LRW (after removal of the monoubiquitin), which had also served as the homology template for our previous work on OTUD7A, was chosen for the virtual screen, with the binding site located between residues W234, Q237, Q238, T239, Q241, N242, S245, G246, L247, Y249, W254, E257, W258, E260, L261, L264, L294, E295, E296, F297, H298, P330, F331, H390, and F391."
OTUD7B affects mRFP-GFP-LC3
| 1
OTUD7B activates mRFP-GFP-LC3. 1 / 1
| 1

reach
"These results indicated that Cezanne might promote autophagy at the autophagosome formation stage.The mRFP-GFP-LC3 was used to show the number of autophagosomes and the autophagosome maturation."
| 1
OTUD7B decreases the amount of glutathione. 1 / 1
| 1

reach
"In vitro, OTUD7B knockdown yielded similar results, marked by decreased SOD activity, reduced GSH levels, increased MDA content, elevated ACSL4 protein expression, and reduced xCT and GPX4 protein expression (Fig. 4C, D, E, G)."
OTUD7B affects deubiquitinase enzyme
| 1
OTUD7B inhibits deubiquitinase enzyme. 1 / 1
| 1

reach
"Of the targets shown in Fig. 1, an inhibitor of the deubiquitinase enzyme (DUB), OTUD7B, could specifically activate the non-canonical NFkB pathway."
| 1
| 1

reach
"ELISA and tube formation assay revealed OTUD7B promotes VEGF production and angiogenesis."
OTUD7B affects ZDHHC17
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No evidence text available
OTUD7B affects WWOX
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1 |

No evidence text available
OTUD7B affects VIRMA
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1 |

No evidence text available
OTUD7B affects US7
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1 |

No evidence text available
OTUD7B affects UBA domain
| 1
OTUD7B binds K63-, and UBA domain. 1 / 1
| 1

reach
"We confirmed the binding of the UBA domain of Cezanne and Cezanne2 to K63-, but not K48- or K11-tetra-ubiquitin in the in vitro pull-down assay using purified recombinant GST-tagged protein fragments and linkage-specific ubiquitin chains (Fig. 1B)."
OTUD7B affects TP53BP1
| 1
| 1

reach
"The different roles of Cezanne and Cezanne2 in promoting Rap80 or Rad18 and 53BP1 suggest that the K63-dependent recruitments of DNA repair proteins are differentially regulated by Cezanne and Cezanne2."
OTUD7B affects TOPflash
| 1
OTUD7B activates TOPflash. 1 / 1
| 1

reach
"Compared to FOPflash luciferase levels, both USP36 and OTUD7B increased the luciferase activities (TOPflash), but OTUD7B significantly enhanced LEF1 activity to a greater extent (6.64-fold) than USP36 did (2.04-fold) (Figure 1C)."
OTUD7B affects TNIP2
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1 |

No evidence text available
OTUD7B affects TNFRSF1A
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No evidence text available
OTUD7B affects TNFAIP3
| 1

sparser
"Here, we identified that the A20-mediated dynamic change of RIPK1 ubiquitination, resulted in a shift of the targeted ubiquitin chains of OTUD7B from K63 to K48 of RIPK1, and that OTUD7B interacted with A20 and diminished K48 polyubiquitination of RIPK1."
OTUD7B affects TNF receptor
| 1
OTUD7B binds TNF receptor. 1 / 1
| 1

reach
"Cezanne recruitment to the activated TNF receptor leads to strongly diminished RIP1 polyubiquitylation."
OTUD7B affects Sal-miR-1 3-induced upregulation SMC-specific contractile proteins
| 1
OTUD7B activates Sal-miR-1 3-induced upregulation SMC-specific contractile proteins. 1 / 1
| 1

eidos
"Also , Sal-miR-1 and 3-induced upregulation of SMC-specific contractile proteins ( SM alpha-actin , SM22alpha , calponin and SMMHC ) , which were suppressed in thrombin-treated VSMCs , was largely enhanced by OTUD7B knockdown ( Figure 3M ) ."
OTUD7B affects SHBG
| 1
OTUD7B binds DiUb and SHBG. 1 / 1
| 1

sparser
"A detailed analysis of internal K11-linked diUb ABP binding to Cezanne revealed that recognition of S1′ site ubiquitin leads to a large dynamic conformational change and subsequent catalysis in Cezanne."
| PMC
OTUD7B affects SAXO4
1 |
1 |

No evidence text available
OTUD7B decreases the amount of Reactive Oxygen Species. 1 / 1
| 1

reach
"Collectively, these findings suggested that Cezanne alleviated DOX-induced apoptosis in NRCMs.At the same time, we observed that Cezanne overexpression in NRCMs reduced the high level of ROS induced b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B affects RIPK
| 1
OTUD7B leads to the deubiquitination of RIPK. 1 / 1
| 1

reach
"Upon TNF-α stimulation Cezanne is recruited to TNFR1 and promotes RIP de-ubiquitination, thereby attenuating NF-κB signaling [121] ."
OTUD7B affects RCOR1
| 1
| 1

reach
"Notably, we were unable to detect any significant interaction between OTUD7B and CoREST when both were ectopically expressed, even in cells expressing ectopic LSD1 (Figure S1E, Supporting Information)."
OTUD7B affects RAS
| 1
OTUD7B inhibits RAS. 1 / 1
| 1

reach
"Further mechanistic studies reveal that OTUD7B associates with RASGRF1 and PLCE1 to disrupt RAS signaling pathway."
OTUD7B affects PSMB1
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1 |

No evidence text available
OTUD7B affects PIK3 C3
| 1
OTUD7B inhibits PIK3 C3. 1 / 1
| 1

eidos
"Mechanistically , we demonstrated that STAMBP / AMSH ( STAM-binding protein ) promotes the stabilization of ULK1 by removing its lysine 48 ( K48 ) - linked ubiquitination , whereas OTUD7B mediates the degradation of PIK3 C3 by enhancing its K48-linked ubiquitination , thus positively or negatively affects autophagy flux , respectively ."
OTUD7B affects PI3K/AKT/mTOR
| 1
OTUD7B increases the amount of PI3K/AKT/mTOR. 1 / 1
| 1

reach
"Conversely, Cezanne overexpression in NRCMs restored the phosphorylation level of the PI3K/AKT/mTOR pathway ( Fig. 5 B)."
OTUD7B affects PHD-mediated HIF-1alpha hydroxylation
| 1
OTUD7B activates PHD-mediated HIF-1alpha hydroxylation. 1 / 1
| 1

eidos
"Further , the effects of OTUD7B on HIF-1alpha were not dependent on PHD-mediated HIF-1alpha hydroxylation , but required VHL ."
OTUD7B affects OTUD7B
| 1
OTUD7B deubiquitinates OTUD7B. 1 / 1
| 1

reach
"These data indicated that OTUD7B interacts with and deubiquitylates KLF4 and OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels."
OTUD7B affects OTU
| 1
OTUD7B activates OTU. 1 / 1
| 1

reach
"Mechanical low shear stress activates hypoxia-inducible factor 1α (HIF-1α) in cultured VECs through the nuclear factor-kB (NF-kB) pathway, leading to the upregulation of OTU deubiquitinating enzyme 7B (Cezanne)."
OTUD7B affects Nephritis
| 1
| 1

reach
"Hypoxia-induced upregulation of Cezanne impedes NF-κB signaling by inhibiting ubiquitination of the tumor necrosis factor receptor-associated factor 6 (TRAF6), and Cezanne knockout promoted ischemia-r[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B affects NIK processing p100
| 1
OTUD7B activates NIK processing p100. 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 ) ."
OTUD7B affects NF-kappaB-Lin28
| 1
OTUD7B inhibits NF-kappaB-Lin28. 1 / 1
| 1

reach
"In silico analysis suggested that OTUD7B regulation, probably owing to miR-1180 downregulation, may negatively regulate the NF-kappaB-Lin28 axis which in turn triggers Let-7 microRNA mediated caspase-3 downregulation, thereby conferring paclitaxel resistance in TNBCs."
OTUD7B affects NF-kappaB pathway liver cancer
| 1
OTUD7B inhibits NF-kappaB pathway liver cancer. 1 / 1
| 1

eidos
"A previous study showed that OTUD7B can inhibit the NF-kappaB pathway in liver cancer [ 33 ] ."
OTUD7B affects MTSS2
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1 |

No evidence text available
OTUD7B affects METTL14
| 1

sparser
"These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC."
OTUD7B affects ME1
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1 |

No evidence text available
OTUD7B affects MDM2
| 1
| 1

sparser
"Since the aforementioned IP assays showed that OTUD7B does not directly bind with Mdm2 (Figure xref F), these data suggest that the effects on Mdm2 following OTUD7B knockdown largely depend upon changes in p53."
OTUD7B affects MBD2
| 1
OTUD7B deubiquitinates MBD2 on lysine. 1 / 1
| 1

reach
"OTU deubiquitinase 7B (OTUD7B) deubiquitinates lysine-specific demethylase 1 (LSD1) to decrease histone H3 lysine 4 (H3K4)/H3K9 methylation, thereby sustaining breast cancer metastasis potential 103.Overexpression of miR-7 in BCSCs decreases endothelial cell adhesion molecule (ESAM) expression by targeting RelA and inhibits tumorigenesis and distant lung metastasis 104."
OTUD7B affects LGR4
1 |
1 |

No evidence text available
OTUD7B affects LEF1/β-catenin
| 1
LEF1/β-catenin binds OTUD7B. 1 / 1
| 1

reach
"Instead, a more effective approach could involve the use of small peptides that interfere with the interaction between LEF1/β-catenin and OTUD7B."
OTUD7B affects LDB19
1 |
1 |

No evidence text available
OTUD7B affects LC3B-II
| 1
OTUD7B activates LC3B-II. 1 / 1
| 1

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"Then, to validate the hypothesis, we conducted a further study to investigate the autophagy flux change which showed that Cezanne could promote autophagy activation, that Cezanne promoted the transformation of LC3B-II and the formation of autophagosome (Fig. 2B–F)."
OTUD7B affects LC3B-I
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OTUD7B activates LC3B-I. 1 / 1
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"As shown in Fig. 2B, the knockdown of Cezanne inhibited the transformation of LC3B-I to LC-3B-II even without an autophagy inducer, and Cezanne overexpression promoted this transformation (Fig. 2C–F)."
OTUD7B affects Kr
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OTUD7B inhibits Kr. 1 / 1
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"Notably, OTUD7B suppressed CH progression by activating AKT signaling cascades and regulating KLF4 (Krüppel‐like factor 4) degradation."
OTUD7B affects KLF4 protein clarify
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OTUD7B activates KLF4 protein clarify. 1 / 1
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"OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels To clarify which substrate is regulated and deubiquitinated by OTUD7B in the context of VSMC migration and adhesion , we used 3 protein-protein interaction prediction databases ( Cytoscape : http://apps.cytoscape.org/apps/agilentliteraturesearch; inBio-Map : https://www.intomics.com/inbio/map.html#search; Genemania : http://genemania.org ) to search for putative proteins interacting with OTUD7B ."
OTUD7B affects K63-polyubiquitin chains
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OTUD7B inhibits K63-polyubiquitin chains. 1 / 1
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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."
OTUD7B affects K63-,
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OTUD7B binds K63-, and UBA domain. 1 / 1
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"We confirmed the binding of the UBA domain of Cezanne and Cezanne2 to K63-, but not K48- or K11-tetra-ubiquitin in the in vitro pull-down assay using purified recombinant GST-tagged protein fragments and linkage-specific ubiquitin chains (Fig. 1B)."
OTUD7B affects IFNGR2
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"Additionally, deletion analysis demonstrated that OTUD7B physically interacted with the AF1 domain of ERα (Fig. xref )."
OTUD7B affects IFNG
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OTUD7B activates IFNG. 1 / 1
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"Additionally, in vitro differentiated Otud7b -/- Th1 cells produced less IFNgamma, a result that was substantiated by in vivo experiments showing that Otud7b -/- mice generated fewer Th1 cells in response to bacterial infection or during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis."
OTUD7B affects ICAM1
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OTUD7B inhibits ICAM1. 1 / 1
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"Silencing of Cezanne using a pool of siRNA sequences from an alternative source also significantly enhanced the induction of E-selectin, VCAM-1 and ICAM-1 in EC exposed to hypoxia-reoxygenation (Online Fig. VI)."
OTUD7B affects Histone_H3
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OTUD7B leads to the demethylation of Histone_H3 on lysine. 1 / 1
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"OTU deubiquitinase 7B (OTUD7B) deubiquitinates lysine-specific demethylase 1 (LSD1) to decrease histone H3 lysine 4 (H3K4)/H3K9 methylation, thereby sustaining breast cancer metastasis potential 103.Overexpression of miR-7 in BCSCs decreases endothelial cell adhesion molecule (ESAM) expression by targeting RelA and inhibits tumorigenesis and distant lung metastasis 104."
OTUD7B affects HNRNPH1
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No evidence text available
OTUD7B affects HMG domain
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OTUD7B binds LEF1 and HMG domain. 1 / 1
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"This result demonstrates that OTUD7B binds to LEF1 through its HMG domain."
OTUD7B affects HIF-1alpha VHL dependent manner independent PHD-mediated prolyl hydroxylation
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OTUD7B activates HIF-1alpha VHL dependent manner independent PHD-mediated prolyl hydroxylation. 1 / 1
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eidos
"Loss of OTUD7B leads to degradation of HIF-1alpha in a VHL dependent manner independent of PHD-mediated prolyl hydroxylation [ 69,82 ] ."
OTUD7B affects HIF-1alpha HIF-2alpha
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OTUD7B activates HIF-1alpha HIF-2alpha. 1 / 1
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"However , the knockdown of OTUD7B decreased HIF-1alpha and HIF-2alpha levels and increased K11 linkages on HIF-1alpha , but not K48 linkages ."
OTUD7B affects H3K9me2
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OTUD7B activates H3K9me2. 1 / 1
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"Importantly, in LSD1‐reconstituted cells, LSD1 rendered their promoters resistant to OTUD7B ablation‐induced H3K4me2/H3K9me2 alterations (Figure 6J,L)."
OTUD7B affects H3K9
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OTUD7B leads to the methylation of H3K9. 1 / 1
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"Consequently, OTUD7B deficiency impairs genome-wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis."
OTUD7B affects GbetaL
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OTUD7B leads to the deubiquitination of GbetaL. 1 / 1
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"Deletion of Otud7b did not significantly affect Akt ubiquitination, but largely abolished the decrease of GbetaL ubiquitination in cells induced by growth factor stimulation (XREF_FIG and XREF_FIG)."
OTUD7B affects G_protein
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OTUD7B decreases the amount of G_protein. 1 / 1
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"OTU deubiquitinase 7B (OTUD7B) diminishes the ubiquitination amount of G protein β-like (GβL), prevents GβL binding to SIN1, resulting in mTORC2/AKT signaling upregulation and conversely the downregulation of mTORC1 activity."
OTUD7B affects GST
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sparser
"GSTOTUD7B and GST‐LSD1 were generated by subcloning the corresponding cDNAs into the pGEX4T1 expressing vector via BamHI and XhoI sites."
OTUD7B affects GPX4
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OTUD7B decreases the amount of GPX4. 1 / 1
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"In vitro, OTUD7B knockdown yielded similar results, marked by decreased SOD activity, reduced GSH levels, increased MDA content, elevated ACSL4 protein expression, and reduced xCT and GPX4 protein expression (Fig. 4C, D, E, G)."
OTUD7B affects Fever
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OTUD7B inhibits Fever. 1 / 1
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"Overexpressing OTUD7B enhanced the anti-cancer effect of hyperthermia, while si-OTUD7B reversed the anti-cancer effect of hyperthermia, which was verified in the xenograft tumor model in nude mice."
OTUD7B affects F_actin
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"However, Traf6 depletion has a minimal effect on the formation of F-actin microspikes induced by ZA20D1 depletion (XREF_FIG) and ZA20D1 depletion has no effect on the levels of phosphorylation of IKKalpha and beta and IkappaB (XREF_FIG and data not shown)."
OTUD7B affects FAO-related genes
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OTUD7B decreases the amount of FAO-related genes. 1 / 1
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"These results indicate that OTUD7B knockdown leads to the downregulation of FAO-related genes, potentially due to the decreased level of HNF4α suppressing the transcription of FAO-related genes."
OTUD7B affects FAM168A
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No evidence text available
OTUD7B affects ETS2
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OTUD7B activates ETS2. 1 / 1
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"USP39 suppressed the transcription activity of ETS2 by approximately 72.8%, while OTUD7A and OTUD7B increased the transcription activity of ETS2 by approximately 55.2% and 68.5%, respectively."
OTUD7B affects ESR
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OTUD7B deubiquitinates ESR. 1 / 1
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"In ERα-positive breast cancer, OTUD7B deubiquitylates ERα, leading to its stabilization; through this mechanism, OTUD7B promotes the proliferation of breast cancer cells (15)."
OTUD7B affects ERK
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OTUD7B leads to the dephosphorylation of ERK. 1 / 1
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"Otud7b deficiency inhibited TCR-CD28-stimulated phosphorylation of Zap70, Akt, and Erks in both naive CD4 + T cells (XREF_FIG) and naive CD8 + T cells (XREF_FIG)."
OTUD7B affects EPM2AIP1
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No evidence text available
OTUD7B affects EFGR
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OTUD7B activates EFGR. 1 / 1
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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 DiUb
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OTUD7B binds DiUb and SHBG. 1 / 1
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sparser
"A detailed analysis of internal K11-linked diUb ABP binding to Cezanne revealed that recognition of S1′ site ubiquitin leads to a large dynamic conformational change and subsequent catalysis in Cezanne."
| PMC
OTUD7B affects DNA Damage
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"In cells microirradiated with a laser, GFP-tagged Cezanne accumulated at laser-induced DNA damage, and lack of the UBA domain (ΔUBA mutant) abolished the recruitment of Cezanne to DNA damage sites, indicating that Cezanne localization to DNA damage sites depends on the UBA domain (Fig. 6A)."
OTUD7B affects DIABLO
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"Next, co-IP validation showed that OTUD7B interacted with Smac and stabilized Smac through deubiquitination."
OTUD7B affects DET1
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sparser
"Our results indicate that OTUD7B and CUL4A DET1-COP1 exert opposite roles in regulating Sox2 protein stability at the post-translational level."
OTUD7B affects DAZAP2
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No evidence text available

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"OTUD7B promotes apoptosis of hepatocellular carcinoma cells through p53."
OTUD7B affects CUL4A
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sparser
"Our results indicate that OTUD7B and CUL4A DET1-COP1 exert opposite roles in regulating Sox2 protein stability at the post-translational level."
OTUD7B affects CUL3
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No evidence text available
OTUD7B affects CRAT
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OTUD7B activates CRAT. 1 / 1
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"In contrast, overexpression of OTUD7B led to an increase in HNF4α and ACOT1 expression (Fig. 6C), and significantly upregulated the transcription of FAO genes (Acot1, Cd36, Cpt2, Crat, Cpt1b, and Acadm) after PE stimulation (Fig. 6D)."
OTUD7B affects CPT2
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OTUD7B activates CPT2. 1 / 1
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"In contrast, overexpression of OTUD7B led to an increase in HNF4α and ACOT1 expression (Fig. 6C), and significantly upregulated the transcription of FAO genes (Acot1, Cd36, Cpt2, Crat, Cpt1b, and Acadm) after PE stimulation (Fig. 6D)."
OTUD7B affects CD40
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OTUD7B inhibits CD40. 1 / 1
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"In line with this, OTUD7b-deficient MEFs increased K48-linked TRAF3 ubiquitination and have increased activation of the noncanonical pathway in response to CD40, B cell-activating factor receptor (BAF[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B affects CARD16
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sparser
"Our results indicate that OTUD7B and CUL4A DET1-COP1 exert opposite roles in regulating Sox2 protein stability at the post-translational level."
OTUD7B affects BCL2
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OTUD7B decreases the amount of BCL2. 1 / 1
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"In this study, Cezanne knockdown in NRCMs using Ad-shCezanne significantly decreased the levels of Bax and Bcl-2, two makers of apoptosis-related family, confirmed by Western blot and immunofluorescen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B affects BAX
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OTUD7B decreases the amount of BAX. 1 / 1
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"In this study, Cezanne knockdown in NRCMs using Ad-shCezanne significantly decreased the levels of Bax and Bcl-2, two makers of apoptosis-related family, confirmed by Western blot and immunofluorescen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Various E3 ubiquitin ligases and deubiquitinases (DUBs), including Pellino 1, Itch, c-Cbl, Cbl-b, GRAIL, and OTUD7B, have been identified to negatively regulate TCR-CD28 signal transduction and preven[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD7B affects AMD1
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OTUD7B activates AMD1. 1 / 1
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"We analyzed Otud7b -/- mice, which were subjected to light-induced damage, a dry AMD model, or were mated with an RP mouse model, and observed increased cone photoreceptor degeneration."
OTUD7B affects ACTA1
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OTUD7B decreases the amount of ACTA1. 1 / 1
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"However, OTUD7B overexpression significantly reduced cardiomyocyte hypertrophy and downregulated the mRNA expressions of NPPA, NPPB, Myh7, and Acta1 compared with those in the AdVector phenylephrine control group (Figure 4E and 4F)."
OTUD7B affects ACADM
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OTUD7B activates ACADM. 1 / 1
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"In contrast, overexpression of OTUD7B led to an increase in HNF4α and ACOT1 expression (Fig. 6C), and significantly upregulated the transcription of FAO genes (Acot1, Cd36, Cpt2, Crat, Cpt1b, and Acadm) after PE stimulation (Fig. 6D)."
OTUD7B inhibitor affects OTUD7B
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OTUD7B inhibitor activates OTUD7B. 1 / 1
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"We validated the effects of the OTUD7B inhibitor (7Bi) in reducing Akt-pS473 signals in multiple NSCLC and HEK293 cells by blocking OTUD7B-governed GbetaL deubiquitination in cells, as well as inhibiting OTUD7B-mediated cleavage of K11-linked di-ub in an in vitro enzyme assay."

reach
"In addition, both the RHBDL2-SA and RHBDL2 plus OTUD7B-silencing groups significantly reversed the increased expression levels of the Notch signaling pathway downstream target genes (HES1, HEY1, ZEB1, MMP9, SNAIL1, and TWIST1) and cleaved Notch1 (Fig. 7F, G), as well as the enhanced luciferase reporter activity (Fig. 7H) mediated by the RHBDL2."
NR2F2 affects OTUD7B
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NR2F2 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
NFE2 affects OTUD7B
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NFE2 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
MTSS2 affects OTUD7B
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1 |

No evidence text available
MIR587 affects OTUD7B
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MIR587 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
MIR1321 affects OTUD7B
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MIR1321 decreases the amount of OTUD7B. 1 / 1
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No evidence text available
METTL14 affects OTUD7B
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sparser
"These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC."
MEF2A affects OTUD7B
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MEF2A decreases the amount of OTUD7B. 1 / 1
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No evidence text available
ME1 affects OTUD7B
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No evidence text available
MDM2 affects OTUD7B
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sparser
"Since the aforementioned IP assays showed that OTUD7B does not directly bind with Mdm2 (Figure xref F), these data suggest that the effects on Mdm2 following OTUD7B knockdown largely depend upon changes in p53."
LGR4 affects OTUD7B
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No evidence text available
LEF1/β-catenin affects OTUD7B
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LEF1/β-catenin binds OTUD7B. 1 / 1
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"Instead, a more effective approach could involve the use of small peptides that interfere with the interaction between LEF1/β-catenin and OTUD7B."
LEF1 affects HMG domain
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OTUD7B binds LEF1 and HMG domain. 1 / 1
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"This result demonstrates that OTUD7B binds to LEF1 through its HMG domain."
LDB19 affects OTUD7B
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1 |

No evidence text available
K63-, affects UBA domain
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OTUD7B binds K63-, and UBA domain. 1 / 1
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"We confirmed the binding of the UBA domain of Cezanne and Cezanne2 to K63-, but not K48- or K11-tetra-ubiquitin in the in vitro pull-down assay using purified recombinant GST-tagged protein fragments and linkage-specific ubiquitin chains (Fig. 1B)."
IFNGR2 affects OTUD7B
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sparser
"Additionally, deletion analysis demonstrated that OTUD7B physically interacted with the AF1 domain of ERα (Fig. xref )."
HNRNPH1 affects OTUD7B
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No evidence text available
HMG domain affects OTUD7B
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OTUD7B binds LEF1 and HMG domain. 1 / 1
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"This result demonstrates that OTUD7B binds to LEF1 through its HMG domain."
GST affects OTUD7B
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sparser
"GSTOTUD7B and GST‐LSD1 were generated by subcloning the corresponding cDNAs into the pGEX4T1 expressing vector via BamHI and XhoI sites."
FIH affects OTUD7B
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FIH hydroxylates OTUD7B on lysine. 1 / 1
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"In addition, several DUBs are hydroxylated by FIH, including OTUB1 (Scholz et al, 2016) and Cezanne, a Lysine 11 specific DUB (Mader et al, 2020)."
FAM168A affects OTUD7B
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No evidence text available

reach
"Studies of cultured endothelial cells (EC) demonstrated that hypoxia (1% oxygen) induced Cezanne via p38 MAP kinase-dependent transcriptional and post- transcriptional mechanisms."
ESR1 affects IFNGR2, and OTUD7B
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"Additionally, deletion analysis demonstrated that OTUD7B physically interacted with the AF1 domain of ERα (Fig. xref )."
EPM2AIP1 affects OTUD7B
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No evidence text available
DiUb affects SHBG
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OTUD7B binds DiUb and SHBG. 1 / 1
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sparser
"A detailed analysis of internal K11-linked diUb ABP binding to Cezanne revealed that recognition of S1′ site ubiquitin leads to a large dynamic conformational change and subsequent catalysis in Cezanne."
| PMC
DIABLO affects OTUD7B
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"Next, co-IP validation showed that OTUD7B interacted with Smac and stabilized Smac through deubiquitination."
DET1 affects OTUD7B
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sparser
"Our results indicate that OTUD7B and CUL4A DET1-COP1 exert opposite roles in regulating Sox2 protein stability at the post-translational level."
DDE affects OTUD7B
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DDE decreases the amount of OTUD7B. 1 / 1
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No evidence text available
DAZAP2 affects OTUD7B
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No evidence text available
CUL4A affects OTUD7B
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sparser
"Our results indicate that OTUD7B and CUL4A DET1-COP1 exert opposite roles in regulating Sox2 protein stability at the post-translational level."
CUL3 affects OTUD7B
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1 |

No evidence text available
CARD16 affects OTUD7B
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sparser
"Our results indicate that OTUD7B and CUL4A DET1-COP1 exert opposite roles in regulating Sox2 protein stability at the post-translational level."
Bulk RNA-seq data affects OTUD7B
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Bulk RNA-seq data activates OTUD7B. 1 / 1
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"Bulk RNA-seq data from both Ang II-induced hypertrophic mice and hypertrophic cardiomyopathy patients further confirmed OTUD7B as one of the significantly downregulated members of the OTU family."
ATP12A affects OTUD7B
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ATP12A decreases the amount of OTUD7B. 1 / 1
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No evidence text available
ATF2 affects OTUD7B
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ATF2 activates OTUD7B. 1 / 1
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"We observed that silencing of ATF2 using two different siRNA sequences suppressed the induction of Cezanne by hypoxia (Fig. 2B)."

No evidence text available

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"Cezanne activity can also be rescued by DTT (Fig. S4C)."
% oxygen affects OTUD7B
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% oxygen activates OTUD7B. 1 / 1
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"Methods and Results Studies of cultured endothelial cells ( EC ) demonstrated that hypoxia ( 1 % oxygen ) induced Cezanne via p38 MAP kinase-dependent transcriptional and post - transcriptional mechanisms ."
1 |

No evidence text available