IndraLab

Statements


OTUD3 affects PTEN
1 4 1 | 1 5 19 1
OTUD3 binds PTEN.
4 | 3 19
4 | 3 17

No evidence text available

sparser
"miR-520h Regulates OTUD3-PTEN and Breast Cancer Progression."

sparser
"To determine whether miR-520h expression and the OTUD3-PTEN axis are associated with the clinicopathological characteristics of breast cancer patients, 156 pairs of tumor tissues and adjacent normal tissues were analyzed by RT-PCR and immunohistochemistry (IHC)."

No evidence text available

sparser
"The expression change of OTUD3-PTEN signaling axis in glioma cells."

No evidence text available

sparser
"Finally, the interaction between OTUD3 and PTEN was not observed in lung cancer cells, and OTUD3 turned to interact with another substrate GRP78, a regulator which could promote tumorigenesis, metastasis and drug resistance in cancers xref – xref ."

sparser
"Here we showed PTEN interacts with OTUD3 and influences stability of its downstream protein TOP2A, and this represents a novel mechanism by which PTEN regulates levels of its downstream targets."

sparser
"We sought to determine which of these PTEN associated deubiquitinases associate with TOP2A, and found OTUD3 can associate with TOP2A. Co-IP assays confirmed interaction of PTEN and OTUD3 ( xref lane 3)."

sparser
"In this study, we demonstrated that the mechanism through which miR-520h induces drug resistance involves the OTUD3-PTEN axis."
OTUD3 binds PTEN and polyubiquitin. 1 / 1
| 1

sparser
"For example, stabilization of NF-κB/RelA by USP48 [ xref ], stabilization of MCL1 by USP9X [ xref ], and stabilization of PTEN by OTUD3 [ xref ] are associated with the cleavage of K48-linked polyubiquitin from the substrate."
USP13 binds OTUD3 and PTEN. 1 / 1
| 1

sparser
"USP7, a highly expressed DUB in prostate cancer and progressive multifocal leukoencephalopathy (PML), plays a direct role in PTEN deubiquitination and regulates its localization rather than protein stability. xref In addition, USP13 and OTUD3 can interact with PTEN and remove its polyubiquitin chain."
OTUD3 deubiquitinates PTEN.
1 1 | 2
OTUD3 deubiquitinates PTEN. 3 / 3
1 | 2

reach
"It is worth mentioning that OTUD3 is decreased in breast cancer and suppresses tumorigenesis by deubiquitinating PTEN 70."

reach
"Our previous results showed that OTUD3 can deubiquitinate and stabilize PTEN."

"Here, we report OTUD3 as a deubiquitylase of PTEN. OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN."
OTUD3 deubiquitinates PTEN on lysine. 1 / 1
1 |

No evidence text available
OTUD3 increases the amount of PTEN.
| 1
OTUD3 increases the amount of PTEN. 1 / 1
| 1

isi
"Western blot was performed to assay PTEN and OTUD3 protein expression in C6 cells and primary astrocytes."
OTUD3 activates PTEN.
| 1
OTUD3 activates PTEN. 1 / 1
| 1

eidos
"Depletion of OTUD3 dramatically decreased PTEN levels , and two independent OTUD3 shRNAs showed significant effects ( Supplementary Fig. 3a , b ) ."
OTUD3 affects TP53
| 17 13 1
OTUD3 binds TP53.
| 7 13 1
| 7 13

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"The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments."

sparser
"To determine whether the OTUD3-TP53 interaction was direct, we generated and purified recombinant Myc-OTUD3, Myc-D1 and Myc-D2."

sparser
"OTUD3 interacts with p53."

sparser
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."

sparser
"The finding that OTUD3 potentially binds the N-terminus of p53 may suggest that both Mdm2 and OTUD3 compete for the same binding site in p53, possibly explaining the observed effects of OTUD3 overexpression and knockdown on p53 ubiquitination and p53 levels in cells."

sparser
"In summary, we found that OTUD3 may be a potential therapeutic target for restoring p53 function in breast cancer cells and suggest that the OTUD3-p53 signaling axis may play a critical role in tumor suppression."

sparser
"To determine the region where p53 binds OTUD3, we also constructed truncated p53 mutants (Fig. xref f) and performed GST assays."

sparser
"Using the D1 and D2 constructs in co-immunoprecipitation experiments, we revealed that the OTU domain-containing region D1 (1–183) is critical for the interaction between OTUD3 and p53 (Fig. xref d)."

reach
"The finding that OTUD3 potentially binds the N-terminus of p53 may suggest that both Mdm2 and OTUD3 compete for the same binding site in p53, possibly explaining the observed effects of OTUD3 overexpression and knockdown on p53 ubiquitination and p53 levels in cells."

sparser
"The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments."
TP53 binds OTUD3. 1 / 1
| 1

isi
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."
OTUD3 deubiquitinates TP53.
| 6
OTUD3 deubiquitinates TP53. 6 / 6
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reach
"OTUD3 likely deubiquitinates p53 to counteract the action of the E3 ubiquitin ligase Mdm2."

reach
"OTUD3 deubiquitinates p53."

reach
"As indicated in Fig. 5a, a high level of ubiquitinated p53 was found in the MCF7 and DU4475 cells transfected with Mdm2 (lane 2); however, p53 ubiquitination was significantly abrogated by OTUD3 expression (comparison of lanes 3 and 2)."

reach
"As OTUD3 is a deubiquitinase, we examined whether OTUD3 deubiquitinates p53."

reach
"Collectively, these data demonstrate that OTUD3 negatively regulates p53 ubiquitination in breast cancer cells and plays an important role in the balance between p53 ubiquitination and deubiquitination."

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"Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells."
OTUD3 ubiquitinates TP53.
| 2
OTUD3 ubiquitinates TP53. 2 / 2
| 2

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"In contrast, the OTUD3 downregulation by shRNA increased p53 ubiquitination in the MCF7 and DU4475 cells (Fig. 5b)."

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"Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells."
OTUD3 inhibits TP53.
| 1
OTUD3 inhibits TP53. 1 / 1
| 1

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"This spatially separates MDM2 from p53, resulting in the stabilization of the p53 protein and allowing p53 to regulate gene transcription, leading to p21 and BAX expression, cell cycle arrest, and/or cell death.We found that OTUD3 deletion is generally associated with the obliteration of WT p53 in BC, suggesting that OTUD3 loss may be selected by tumors to disrupt the p53 pathway."
OTUD3 activates TP53.
| 1
OTUD3 activates TP53. 1 / 1
| 1

reach
"These results demonstrate that OTUD3 can antagonize the reduction in p53 by Mdm2."
PTEN affects OTUD3
4 | 3 19
4 | 3 17

No evidence text available

sparser
"miR-520h Regulates OTUD3-PTEN and Breast Cancer Progression."

sparser
"To determine whether miR-520h expression and the OTUD3-PTEN axis are associated with the clinicopathological characteristics of breast cancer patients, 156 pairs of tumor tissues and adjacent normal tissues were analyzed by RT-PCR and immunohistochemistry (IHC)."

No evidence text available

sparser
"The expression change of OTUD3-PTEN signaling axis in glioma cells."

No evidence text available

sparser
"Finally, the interaction between OTUD3 and PTEN was not observed in lung cancer cells, and OTUD3 turned to interact with another substrate GRP78, a regulator which could promote tumorigenesis, metastasis and drug resistance in cancers xref – xref ."

sparser
"Here we showed PTEN interacts with OTUD3 and influences stability of its downstream protein TOP2A, and this represents a novel mechanism by which PTEN regulates levels of its downstream targets."

sparser
"We sought to determine which of these PTEN associated deubiquitinases associate with TOP2A, and found OTUD3 can associate with TOP2A. Co-IP assays confirmed interaction of PTEN and OTUD3 ( xref lane 3)."

sparser
"In this study, we demonstrated that the mechanism through which miR-520h induces drug resistance involves the OTUD3-PTEN axis."
OTUD3 binds PTEN and polyubiquitin. 1 / 1
| 1

sparser
"For example, stabilization of NF-κB/RelA by USP48 [ xref ], stabilization of MCL1 by USP9X [ xref ], and stabilization of PTEN by OTUD3 [ xref ] are associated with the cleavage of K48-linked polyubiquitin from the substrate."
USP13 binds OTUD3 and PTEN. 1 / 1
| 1

sparser
"USP7, a highly expressed DUB in prostate cancer and progressive multifocal leukoencephalopathy (PML), plays a direct role in PTEN deubiquitination and regulates its localization rather than protein stability. xref In addition, USP13 and OTUD3 can interact with PTEN and remove its polyubiquitin chain."
TP53 affects OTUD3
| 7 13 1
| 7 13

reach
"The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments."

sparser
"To determine whether the OTUD3-TP53 interaction was direct, we generated and purified recombinant Myc-OTUD3, Myc-D1 and Myc-D2."

sparser
"OTUD3 interacts with p53."

sparser
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."

sparser
"The finding that OTUD3 potentially binds the N-terminus of p53 may suggest that both Mdm2 and OTUD3 compete for the same binding site in p53, possibly explaining the observed effects of OTUD3 overexpression and knockdown on p53 ubiquitination and p53 levels in cells."

sparser
"In summary, we found that OTUD3 may be a potential therapeutic target for restoring p53 function in breast cancer cells and suggest that the OTUD3-p53 signaling axis may play a critical role in tumor suppression."

sparser
"To determine the region where p53 binds OTUD3, we also constructed truncated p53 mutants (Fig. xref f) and performed GST assays."

sparser
"Using the D1 and D2 constructs in co-immunoprecipitation experiments, we revealed that the OTU domain-containing region D1 (1–183) is critical for the interaction between OTUD3 and p53 (Fig. xref d)."

reach
"The finding that OTUD3 potentially binds the N-terminus of p53 may suggest that both Mdm2 and OTUD3 compete for the same binding site in p53, possibly explaining the observed effects of OTUD3 overexpression and knockdown on p53 ubiquitination and p53 levels in cells."

sparser
"The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments."
TP53 binds OTUD3. 1 / 1
| 1

isi
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."
OTUD3 affects HSPA5
| 1 3 6
OTUD3 binds HSPA5.
| 6
| 6

sparser
"OTUD3 interacts with GRP78."

sparser
"The interaction between OTUD3 and GRP78 observed in lung cancer H1299 cells was hardly detected in MCF7 cells (Supplementary Fig.  xref )."

sparser
"Moreover, purified GST-OTUD3 protein, but not the GST alone, was able to interact with His-GRP78 under cell-free conditions (Fig.  xref ), suggesting a direct interaction between GRP78 and OTUD3."

sparser
"Since OTUD3 is a classical member of the OTU family of the deubiquitylase, we wondered whether OTUD3 specifically interacted with GRP78."

sparser
"Whereafter, the interaction between endogenous OTUD3 and GRP78 was detected in A549 and H1299 cells (Fig.  xref )."

sparser
"These findings demonstrate that CHIP is a negative regulator of OTUD3 and CHIP suppresses lung cancer metastasis through inhibiting OTUD3-GRP78 signaling axis."
OTUD3 activates HSPA5.
| 1 1
OTUD3 activates HSPA5. 2 / 2
| 1 1

eidos
"As OTUD3 binds to and positively regulate GRP78 protein stability , we hypothesized that OTUD3 might increase GRP78 expression via deubiquitylation of GRP78 ."

reach
"OTUD3 positively regulates GRP78, which in turn promotes the growth of LUAD cells68."
OTUD3 increases the amount of HSPA5.
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OTUD3 increases the amount of HSPA5. 1 / 1
| 1

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"Knockdown of CHIP stabilizes OTUD3 which leads to elevated GRP78 levels in lung cancer cells."
OTUD3 deubiquitinates HSPA5.
| 1
OTUD3 deubiquitinates HSPA5. 1 / 1
| 1

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"OTUD3 plays an oncogenic role in lung cancer cells and promotes the development of lung cancer by directly interacting with GRP78, where OTUD3 deubiquitylates GRP78 and maintains GRP78 stability in vitro and in vivo."

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"These data suggest that OTUD3 can inhibit BC cell proliferation."

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"Compared to the control cells, knockdown of endogenous OTUD3 by shRNA in the MCF7 and DU4475 cells increased the cell proliferation rate."

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"Furthermore, OTUD3 silence promoted proliferation and motility and decreased apoptosis for HCT116 cells and restored partly miR-32-mediated cell proliferation, migration, and antiapoptosis for colon cancer."

reach
"OTUD3 could rescue the accelerated cell proliferation caused by OTUD3 knockdown, but the inactive enzyme mutant OTUD3 could not inhibit the accelerated cell proliferation, indicating that regulation of the effect of OTUD3 on cell proliferation depends on its ubiquitinase activity (Fig. 6b)."

eidos
"OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs ."

reach
"OTUD3 inhibits cell proliferation."

reach
"Finally, ACTN4 was found to be essential for OTUD3 mediated HCC proliferation and metastasis in vitro and in vivo."

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"OTUD3 could rescue the accelerated cell proliferation caused by OTUD3 knockdown, but the inactive enzyme mutant OTUD3 could not inhibit the accelerated cell proliferation, indicating that regulation of the effect of OTUD3 on cell proliferation depends on its ubiquitinase activity (Fig. 6b)."

reach
"In cell lines both derived from blood/lymphocyte and other tissues, the CERES scores (32) were significantly lower than 0 (Fig. 3G), suggesting knockout of OTUD3 would broadly reduce the proliferation rate of various cell lines."
OTUD3 affects TOP2A
| 5 2
OTUD3 binds TOP2A.
| 2 2
| 2 2

reach
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay (XREF_FIG lane 6)."

sparser
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay ( xref lane 6)."

sparser
"This association of OTUD3 and TOP2A was confirmed in MEFs and HCT116 cells ( xref lane 2, 4f lane 3)."

reach
"We sought to determine which of these PTEN associated deubiquitinases associate with TOP2A, and found OTUD3 can associate with TOP2A."
OTUD3 increases the amount of TOP2A.
| 1
Modified OTUD3 increases the amount of TOP2A. 1 / 1
| 1

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"A finding of particular interest is that overexpression of OTUD3 in PTEN +/+ cells but not in PTEN -/- cells upregulates TOP2A protein levels, indicating PTEN is required for OTUD3 function."
OTUD3 deubiquitinates TOP2A.
| 1
OTUD3 leads to the deubiquitination of TOP2A. 1 / 1
| 1

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"In the presence of PTEN, ubiquitination of TOP2A is inhibited by OTUD3."
OTUD3 activates TOP2A.
| 1
OTUD3 activates TOP2A. 1 / 1
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"Overexpression of OTUD3 leads to upregulation of TOP2A in PTEN +/+ cells, but not in PTEN -/- cells (XREF_FIG lane 1 vs lane 2, lane 3 vs lane 4)."
HSPA5 affects OTUD3
| 6
| 6

sparser
"OTUD3 interacts with GRP78."

sparser
"The interaction between OTUD3 and GRP78 observed in lung cancer H1299 cells was hardly detected in MCF7 cells (Supplementary Fig.  xref )."

sparser
"Moreover, purified GST-OTUD3 protein, but not the GST alone, was able to interact with His-GRP78 under cell-free conditions (Fig.  xref ), suggesting a direct interaction between GRP78 and OTUD3."

sparser
"Since OTUD3 is a classical member of the OTU family of the deubiquitylase, we wondered whether OTUD3 specifically interacted with GRP78."

sparser
"Whereafter, the interaction between endogenous OTUD3 and GRP78 was detected in A549 and H1299 cells (Fig.  xref )."

sparser
"These findings demonstrate that CHIP is a negative regulator of OTUD3 and CHIP suppresses lung cancer metastasis through inhibiting OTUD3-GRP78 signaling axis."
STUB1 affects OTUD3
| 1 3 1
STUB1 inhibits OTUD3.
| 1 1
STUB1 bound to OTUD3 inhibits OTUD3. 1 / 1
| 1

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"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
STUB1 inhibits OTUD3. 1 / 1
| 1

eidos
"CHIP interacts with , polyubiquitylates OTUD3 and promotes OTUD3 degradation ."
STUB1 ubiquitinates OTUD3.
| 1
STUB1 ubiquitinates OTUD3. 1 / 1
| 1

reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
STUB1 increases the amount of OTUD3.
| 1
STUB1 increases the amount of OTUD3. 1 / 1
| 1

isi
"Moreover, the expression of CHIP is low in human lung cancer tissues and inversely correlates with OTUD3 expression and GRP78 expression."
STUB1 binds OTUD3.
| 1
| 1

reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
OTUD3 affects RPS20
| 5
OTUD3 ubiquitinates RPS20.
| 2
OTUD3 leads to the ubiquitination of RPS20. 2 / 2
| 2

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"USP21 and OTUD3 antagonize the ubiquitination of eS10 and uS10 that results from integrated stress response (ISR) and ribosome-associated quality control pathway (RQC) (124)."

reach
"Based on our previously established reversibility of RRub events, we suspected that overexpression of wild type USP21 or OTUD3 would induce a more rapid removal of eS10 and uS10 ubiquitylation during recovery from UV-induced stress."
OTUD3 deubiquitinates RPS20.
| 2
OTUD3 deubiquitinates RPS20. 2 / 2
| 2

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"USP21 and OTUD3 deubiquitylate ZNF598 substrates eS10 and uS10."

reach
"Taken together, these results indicate that USP21 or OTUD3 can deubiquitylate both eS10 and uS10, resulting in enhanced readthrough of poly(A)-mediated stall events."
OTUD3 inhibits RPS20.
| 1
OTUD3 inhibits RPS20. 1 / 1
| 1

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"While expression of wild type USP21 or OTUD3 reduced the abundance of both monoubiquitylated eS10 and uS10 in parental HCT116 cells, expression of the inactive variants restored ubiquitylation to steady-state levels (Figure 4E)."
OTUD3 is modified
1 | 1 3
OTUD3 is acetylated.
| 2
OTUD3 is acetylated on K129. 1 / 1
| 1

sparser
"To confirm this, acetyl‐lysine is incorporated into a recombinant OTUD3 to generate a fully Lys129‐acetylated OTUD3 (OTUD3 Lys129‐Ac ) with chemical biology approaches."
OTUD3 is acetylated. 1 / 1
| 1

sparser
"OTUD3 acetylation would be removed upon virus infection, and the DUB activity would be blocked."
OTUD3 is ubiquitinated.
| 1
OTUD3 is ubiquitinated. 1 / 1
| 1

reach
"We speculate that the balance between the Mdm2-mediated ubiquitination and OTUD3-mediated deubiquitination of p53 is critical for p53 stabilization."
OTUD3 is phosphorylated.
1 |
OTUD3 is phosphorylated on S224. 1 / 1
1 |

No evidence text available
OTUD3 is methylated.
| 1
OTUD3 is methylated. 1 / 1
| 1

sparser
"We used data obtained from the cBioPortal database [ xref , xref ] () and found that decreases in OTUD3 mRNA levels may not be due to increased OTUD3 DNA methylation in BC (Fig. xref d)."
TOP2A affects OTUD3
| 2 2
| 2 2

reach
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay (XREF_FIG lane 6)."

sparser
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay ( xref lane 6)."

sparser
"This association of OTUD3 and TOP2A was confirmed in MEFs and HCT116 cells ( xref lane 2, 4f lane 3)."

reach
"We sought to determine which of these PTEN associated deubiquitinases associate with TOP2A, and found OTUD3 can associate with TOP2A."
OTUD3 affects ZNF598
| 4
OTUD3 inhibits ZNF598.
| 2
OTUD3 inhibits ZNF598. 2 / 2
| 2

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"These results are consistent with the hypothesis that USP21 and OTUD3 directly antagonize ZNF598-mediated RRub events."

reach
"First, USP21 and OTUD3 may limit the activity of ZNF598 and other RRub ligases through direct antagonism to prevent spurious RRub."
OTUD3 ubiquitinates ZNF598.
| 1
OTUD3 leads to the ubiquitination of ZNF598. 1 / 1
| 1

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"DUBs in the RQC pathway have begun to be explored, as a recent study showed that among 58 DUBs screened, overexpression of either USP21 or OTUD3 in mammalian cells can cause the removal of ZNF598-specific ribosomal ubiquitination [145]."
OTUD3 deubiquitinates ZNF598.
| 1
OTUD3 leads to the deubiquitination of ZNF598. 1 / 1
| 1

reach
"Similarly, USP21 and OTUD3 antagonized the ZNF598-dependent eS10 ubiquitylation in uS10-KI cells in an activity dependent manner."
| 2 1
| 2

eidos
"OTUD3 accelerates lung cancer cell growth and metastasis via regulating GRP78 To evaluate whether OTUD3 promotes tumor progression through regulating GRP78 , we depleted endogenous GRP78 in OTUD3-overexpressing H1299 and A549 cells and observed that the inhibition of endogenous GRP78 expression attenuated OTUD3-induced cell growth and migration ( Fig. 7a-f ) ."

eidos
"Secondly , although OTUD3 can inhibit tumor growth and metastasis by stabilizing PTEN in breast cancer , hepatocellular cancer , colon cancer , and cervical cancer , loss of OTUD3 suppressed the tumorigenesis of lung cancer in vitro and in vivo ."
| 1

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"Finally, ACTN4 was found to be essential for OTUD3 mediated HCC proliferation and metastasis in vitro and in vivo."
VIRF-2 affects OTUD3
| 3
| 3

sparser
"The slower kinetics for K11-linked diUb likely arises from loss of the S2 site contribution but could also be due to alternating binding of K11 diUb to sites on OTUD3, where the diUb can bind either productively to S1-S1′ or non-productively to S1-S2 sites."

sparser
"The slower kinetics for K11-linked diUb likely arises from loss of the S2 site contribution but could also be due to alternating binding of K11 diUb to sites on OTUD3, where the diUb can bind either productively to S1-S1 0 or non-productively to S1-S2 sites."

sparser
"Additionally, an S2 site on OTUD3 interacting with K11-linked terminal diUb probes was found to provide the linkage specificity."
| PMC
3 |
Pirinixic acid increases the amount of OTUD3.
1 |
Pirinixic acid increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Pirinixic acid decreases the amount of OTUD3.
1 |
Pirinixic acid decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Pirinixic acid activates OTUD3.
1 |

No evidence text available
MiR-32 affects OTUD3
| 3
MiR-32 activates OTUD3.
| 2
MiR-32 activates OTUD3. 2 / 2
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"Dual luciferase reporter assays proved that miR-32 bound to the 3 '-untranslated region (3 '-UTR) of OTU domain containing 3 (OTUD3), suggesting that miR-32 directly targeted OTUD3."

reach
"Therefore, our study indicated that miR-32 enhanced cell proliferation and motility abilities, and inhibited apoptosis by directly targeting OTUD3 in colon cancer cells, which implied that miR-32 was hopeful to be a biomarker or target used for diagnosis and therapy of colon cancer."
MiR-32 decreases the amount of OTUD3.
| 1
Modified miR-32 decreases the amount of OTUD3. 1 / 1
| 1

reach
"Further experiments demonstrated that overexpression of miR-32 could reduce the expression level of OTUD3."
OTUD3 affects vIRF-2
| 3
| 3

sparser
"The slower kinetics for K11-linked diUb likely arises from loss of the S2 site contribution but could also be due to alternating binding of K11 diUb to sites on OTUD3, where the diUb can bind either productively to S1-S1′ or non-productively to S1-S2 sites."

sparser
"The slower kinetics for K11-linked diUb likely arises from loss of the S2 site contribution but could also be due to alternating binding of K11 diUb to sites on OTUD3, where the diUb can bind either productively to S1-S1 0 or non-productively to S1-S2 sites."

sparser
"Additionally, an S2 site on OTUD3 interacting with K11-linked terminal diUb probes was found to provide the linkage specificity."
| PMC
OTUD3 affects MAVS
| 3
OTUD3 inhibits MAVS.
| 1
OTUD3 inhibits MAVS. 1 / 1
| 1

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"For example, OTUD3 removes K63-linked ubiquitin chains from MAVS and thereby inhibits MAVS aggregation and IFN-I signaling activation (65)."
OTUD3 increases the amount of MAVS.
| 1
OTUD3 increases the amount of MAVS. 1 / 1
| 1

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"In addition, both OTUD3 and A20 negatively regulate the IFN-mediated antiviral response by modulating the polyubiquitination level of MAVS (125, 126)."
OTUD3 decreases the amount of MAVS.
| 1
OTUD3 decreases the amount of MAVS. 1 / 1
| 1

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"In addition, both OTUD3 and A20 negatively regulate the IFN-mediated antiviral response by modulating the polyubiquitination level of MAVS (125, 126)."
OTUD3 affects GRP78 protein
| 3
OTUD3 activates GRP78 protein. 3 / 3
| 3

eidos
"We found that WT OTUD3 , but not C76A mutant , increased GRP78 protein level ( Fig. 6a and Supplementary Fig. 6a ) whereas OTUD3 knockdown remarkably decreased GRP78 protein level ( Fig. 6b and Supplementary Fig. 6b ) ."

eidos
"In consistent with these phenomenon , elevated OTUD3 expression increased GRP78 protein level in the lung tissue of OTUD3 TG mice ( Supplementary Fig. 7c , d ) , whereas OTUD3 knockout decreased GRP78 expression in the mouse lung tissue ( Supplementary Fig. 7e , f ) ."

eidos
"Knockdown of OTUD3 results in a decrease in the level of GRP78 protein , suppression of cell growth and migration , and tumorigenesis in lung cancer ."
OTUD3 affects ACTN4
| 2 1
OTUD3 binds ACTN4.
| 1 1
| 1 1

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"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."

sparser
"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."
OTUD3 deubiquitinates ACTN4.
| 1
OTUD3 deubiquitinates ACTN4. 1 / 1
| 1

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"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."
Paracetamol affects OTUD3
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Paracetamol increases the amount of OTUD3. 2 / 2
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No evidence text available

No evidence text available
Nicotine affects OTUD3
| 1 1
| 1 1

reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."

eidos
"Here we show that OTU domain-containing protein 3 ( OTUD3 ) is downregulated by nicotine and correlates with poor prognosis in heavy-smoking esophageal cancer patients ."
Methyl methanesulfonate increases the amount of OTUD3. 2 / 2
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No evidence text available

No evidence text available
Bisphenol A affects OTUD3
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Bisphenol A increases the amount of OTUD3.
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Bisphenol A increases the amount of OTUD3. 1 / 1
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No evidence text available
Bisphenol A demethylates OTUD3.
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Bisphenol A demethylates OTUD3. 1 / 1
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No evidence text available
USP25 affects OTUD3
| 2
| 2

sparser
"Importantly, both OTUD3 and USP21 are present in the ribosome pellet fraction suggesting that OTUD3 and USP21 associates with ribosomes."

sparser
"Given the ability of USP21 and OTUD3 to remove RRub events, we examined if OTUD3 or USP21 associated with ribosomes."
USP13 affects OTUD3
| 2
| 1

sparser
"PTEN and DUBs were readily co-immunoprecipitated with each other; however, USP11, USP13, and OTUD3 were not associated with each other (Supplementary Fig.  xref )."
USP13 binds OTUD3 and PTEN. 1 / 1
| 1

sparser
"USP7, a highly expressed DUB in prostate cancer and progressive multifocal leukoencephalopathy (PML), plays a direct role in PTEN deubiquitination and regulates its localization rather than protein stability. xref In addition, USP13 and OTUD3 can interact with PTEN and remove its polyubiquitin chain."
UBC affects OTUD3
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No evidence text available

No evidence text available
SIRT1 affects OTUD3
| 1 1
SIRT1 inhibits OTUD3. 2 / 2
| 1 1

sparser
"In response to virus infection, the acetylated Lys129 is removed by SIRT1, which promptly inactivates OTUD3 and thus allows timely induction of innate antiviral immunity."

reach
"In response to virus infection, the acetylated Lys129 is removed by SIRT1, which promptly inactivates OTUD3 and thus allows timely induction of innate antiviral immunity."
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2 |

No evidence text available

No evidence text available
OTUD3 affects tumorigenesis lung cancer
| 2
OTUD3 inhibits tumorigenesis lung cancer.
| 1
OTUD3 inhibits tumorigenesis lung cancer. 1 / 1
| 1

eidos
"Knockdown of OTUD3 results in a decrease in the level of GRP78 protein , suppression of cell growth and migration , and tumorigenesis in lung cancer ."
OTUD3 activates tumorigenesis lung cancer.
| 1
OTUD3 activates tumorigenesis lung cancer. 1 / 1
| 1

eidos
"Secondly , although OTUD3 can inhibit tumor growth and metastasis by stabilizing PTEN in breast cancer , hepatocellular cancer , colon cancer , and cervical cancer , loss of OTUD3 suppressed the tumorigenesis of lung cancer in vitro and in vivo ."
OTUD3 affects migration
| 2
OTUD3 activates migration. 2 / 2
| 2

eidos
"Compared with the control cells , OTUD3 depletion suppressed cell growth and migration ( Fig. 4a , d and supplementary Fig. 4a , c ) ."

eidos
"OTUD3 promotes lung cancer cell growth and migration via GRP78 ."
OTUD3 affects lung cancer cell growth
| 2
OTUD3 inhibits lung cancer cell growth.
| 1
OTUD3 inhibits lung cancer cell growth. 1 / 1
| 1

eidos
"OTUD3 accelerates lung cancer cell growth and metastasis via regulating GRP78 To evaluate whether OTUD3 promotes tumor progression through regulating GRP78 , we depleted endogenous GRP78 in OTUD3-overexpressing H1299 and A549 cells and observed that the inhibition of endogenous GRP78 expression attenuated OTUD3-induced cell growth and migration ( Fig. 7a-f ) ."
OTUD3 activates lung cancer cell growth.
| 1
OTUD3 activates lung cancer cell growth. 1 / 1
| 1

eidos
"OTUD3 promotes lung cancer cell growth and migration via GRP78 ."
| 2

reach
"Furthermore, OTUD3 silence promoted proliferation and motility and decreased apoptosis for HCT116 cells and restored partly miR-32-mediated cell proliferation, migration, and antiapoptosis for colon cancer."

reach
"The results showed that the OTUD3-transfected cells were significantly more sensitive to cisplatin-induced apoptosis than the negative control cells (p < 0.01); however, the sensitivity of the transfected OTUD3 cells was significantly decreased (p < 0.01) (Fig. 7a)."
OTUD3 affects aggregation
| 2
OTUD3 inhibits aggregation. 2 / 2
| 2

eidos
"For example , OTUD3 removes K63-linked ubiquitin chains from MAVS and thereby inhibits MAVS aggregation and IFN-I signaling activation ( 65 ) ."

eidos
"OTU Deubiquitinase 3 ( OTUD3 ) was shown to remove K63-linked ubiquitin chains from MAVS , thereby suppressing MAVS aggregation and downstream activation of type I IFN signaling [ 95 ] ."
OTUD3 affects USP25
| 2
| 2

sparser
"Importantly, both OTUD3 and USP21 are present in the ribosome pellet fraction suggesting that OTUD3 and USP21 associates with ribosomes."

sparser
"Given the ability of USP21 and OTUD3 to remove RRub events, we examined if OTUD3 or USP21 associated with ribosomes."
OTUD3 affects USP13
| 2
| 1

sparser
"PTEN and DUBs were readily co-immunoprecipitated with each other; however, USP11, USP13, and OTUD3 were not associated with each other (Supplementary Fig.  xref )."
USP13 binds OTUD3 and PTEN. 1 / 1
| 1

sparser
"USP7, a highly expressed DUB in prostate cancer and progressive multifocal leukoencephalopathy (PML), plays a direct role in PTEN deubiquitination and regulates its localization rather than protein stability. xref In addition, USP13 and OTUD3 can interact with PTEN and remove its polyubiquitin chain."
OTUD3 affects UBC
2 |
2 |

No evidence text available

No evidence text available
OTUD3 affects Neoplasms
| 2
OTUD3 inhibits Neoplasms.
| 1
| 1

eidos
"OTU domain-containing protein 3 ( OTUD3 ) , as a deubiquitinase ( DUB ) belonging to the ovarian tumor protease ( OTU ) family , has been reported to suppress tumor via OTUD3-PTEN signaling axis ."
OTUD3 activates Neoplasms.
| 1
| 1

eidos
"OTUD3 accelerates lung cancer cell growth and metastasis via regulating GRP78 To evaluate whether OTUD3 promotes tumor progression through regulating GRP78 , we depleted endogenous GRP78 in OTUD3-overexpressing H1299 and A549 cells and observed that the inhibition of endogenous GRP78 expression attenuated OTUD3-induced cell growth and migration ( Fig. 7a-f ) ."
OTUD3 affects ERN1
| 1 1
OTUD3 inhibits ERN1. 2 / 2
| 1 1

eidos
"OTUD3 knockdown resulted in a decrease in the interaction ability of IRE1alpha with Fortilin and finally enhanced the activity of IRE1alpha ."

reach
"Taken together, we revealed that OTUD3 knockout-induced injury of dopaminergic neurons might be caused by activating IRE1α signaling in ER stress."
OTUD3 affects DDX58
| 1 1
DDX58 binds OTUD3 and K63. 1 / 1
| 1

reach
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
| 1

sparser
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
| 1 1
| 1 1

reach
"These results suggested that OTUD3 may promote tumorigenesis in leukemia."

eidos
"These results suggested that OTUD3 may promote tumorigenesis in leukemia ."
DDX58 affects OTUD3
| 1 1
DDX58 binds OTUD3 and K63. 1 / 1
| 1

reach
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
| 1

sparser
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
ACTN4 affects OTUD3
| 1 1
| 1 1

reach
"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."

sparser
"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."
Δ affects OTUD3
| 1
Δ activates OTUD3. 1 / 1
| 1

reach
"Moreover, targeting PPARδ using a specific agonist can partially rescue the phenotype of HFD-fed Otud3 -/- mice."
1 |
Valproic acid increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Urethane affects OTUD3
1 |
Urethane increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Titanium dioxide decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Thioacetamide increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Sodium arsenite increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Sodium arsenate decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Polyubiquitin affects PTEN
| 1
OTUD3 binds PTEN and polyubiquitin. 1 / 1
| 1

sparser
"For example, stabilization of NF-κB/RelA by USP48 [ xref ], stabilization of MCL1 by USP9X [ xref ], and stabilization of PTEN by OTUD3 [ xref ] are associated with the cleavage of K48-linked polyubiquitin from the substrate."
1 |
Methylparaben increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Indometacin affects OTUD3
1 |
Indometacin increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hydroperoxide increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-92b-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-92a-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-769-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6864-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6849-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6771-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6770-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-664a-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6516-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-624-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-513b-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4803 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4794 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4786-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4773 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4768-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4749-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4729 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4671-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4650-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-454-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4493 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4459 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4457 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4433a-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4311 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4295 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-411-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3974 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-379-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3672 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3666 decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-32-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-301b-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-301a-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-216a-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-212-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-20a-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-194-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-192-5p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-132-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-130b-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-130a-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-125b-2-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-1207-3p decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Glucose affects OTUD3
| 1
Glucose leads to the acetylation of OTUD3. 1 / 1
| 1

reach
"We further found that glucose and fatty acids stimulate CREB-binding-protein-dependent OTUD3 acetylation, promoting its nuclear translocation, where OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARδ)."
Endosulfan affects OTUD3
1 |
Endosulfan increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Cisplatin affects OTUD3
1 |
Cisplatin decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
Chains affects OTUD3
| 1
OTUD3 binds chains. 1 / 1
| 1

reach
"Kinetic studies using di‐Ub substrate probes (di‐Ub‐AMC) suggested that the selectivity of OTUD2 for longer K11‐linked chains is driven by affinity (lower KM), while for OTUD3, it appears to be driven by vmax, hinting that binding of K11 chains to OTUD3 may optimally reorganize the active site for catalysis."
1 |
Carbon nanotube increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
CGAS affects OTUD3
| 1
OTUD3 binds cGAS. 1 / 1
| 1

sparser
"Meanwhile, OTUD3 associates with cGAS and targets at Lys279 to deubiquitinate K48-linked ubiquitination, resulting in the enhancement of cGAS protein stability and DNA-binding ability."
ZFP36 affects OTUD3
| 1
| 1

sparser
"OTUD3 directly interacts with ZFP36 ring finger protein (ZFP36) and stabilizes it by inhibiting FBXW7-mediated K48-linked polyubiquitination."
YOD1 affects OTUD3
| 1
YOD1 binds OTUD3 and K11. 1 / 1
| 1

sparser
"Highlights d Protease-resistant diUb probes bind to DUB S1-S2 sites and react at the proximal end d First kinetic assay showing proximal end cleavage by DUBs using diUb-based substrates d OTUD3 binds K11-linked diUb and OTUD2 binds K11-and K33-linked diUb in S1-S2 pockets d Kinetics suggest different mechanisms for polyUb cleavage by OTUD2 and OTUD3 SUMMARY Ubiquitin chains are important post-translational modifications that control a large number of cellular processes."
USP13 affects USP11
| 1
| 1

sparser
"PTEN and DUBs were readily co-immunoprecipitated with each other; however, USP11, USP13, and OTUD3 were not associated with each other (Supplementary Fig.  xref )."
USP13 affects PTEN
| 1
USP13 binds OTUD3 and PTEN. 1 / 1
| 1

sparser
"USP7, a highly expressed DUB in prostate cancer and progressive multifocal leukoencephalopathy (PML), plays a direct role in PTEN deubiquitination and regulates its localization rather than protein stability. xref In addition, USP13 and OTUD3 can interact with PTEN and remove its polyubiquitin chain."
USP11 affects USP13
| 1
| 1

sparser
"PTEN and DUBs were readily co-immunoprecipitated with each other; however, USP11, USP13, and OTUD3 were not associated with each other (Supplementary Fig.  xref )."
TRIM25 affects OTUD3
1 |
1 |

No evidence text available
S1-S1 0 affects OTUD3
| 1
OTUD3 binds S1-S1 0. 1 / 1
| 1

reach
"The slower kinetics for K11-linked diUb likely arises from loss of the S2 site contribution but could also be due to alternating binding of K11 diUb to sites on OTUD3, where the diUb can bind either productively to S1-S1 0 or non-productively to S1-S2 sites."
1 |
Plant Extracts increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
PTEN affects polyubiquitin
| 1
OTUD3 binds PTEN and polyubiquitin. 1 / 1
| 1

sparser
"For example, stabilization of NF-κB/RelA by USP48 [ xref ], stabilization of MCL1 by USP9X [ xref ], and stabilization of PTEN by OTUD3 [ xref ] are associated with the cleavage of K48-linked polyubiquitin from the substrate."
PTEN affects USP13
| 1
USP13 binds OTUD3 and PTEN. 1 / 1
| 1

sparser
"USP7, a highly expressed DUB in prostate cancer and progressive multifocal leukoencephalopathy (PML), plays a direct role in PTEN deubiquitination and regulates its localization rather than protein stability. xref In addition, USP13 and OTUD3 can interact with PTEN and remove its polyubiquitin chain."
PPAR affects OTUD3
| 1
PPAR activates OTUD3. 1 / 1
| 1

reach
"Moreover, targeting PPARδ using a specific agonist can partially rescue the phenotype of HFD-fed Otud3 -/- mice."
OTUD7A affects OTUD3
| 1
| 1

reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
OTUD6B affects OTUD3
| 1
| 1

reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
OTUD4 affects OTUD3
| 1
| 1

reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
OTUD3 affects ubiquitination
| 1
OTUD3 inhibits ubiquitination. 1 / 1
| 1

sparser
"In the presence of PTEN, ubiquitination of TOP2A is inhibited by OTUD3."
OTUD3 affects tumorigenicity
| 1
OTUD3 inhibits tumorigenicity. 1 / 1
| 1

eidos
"To further assess whether OTUD3 is a bona fide tumor suppressor gene , we sought to determine whether loss of OTUD3 expression would induce tumorigenicity ."
OTUD3 affects tumorigenicity tumor metastasis
| 1
OTUD3 inhibits tumorigenicity tumor metastasis. 1 / 1
| 1

eidos
"OTUD3 suppresses tumorigenicity and tumor metastasis ."
OTUD3 affects tumorigenicity lung cancer
| 1
OTUD3 activates tumorigenicity lung cancer. 1 / 1
| 1

eidos
"OTUD3 interacts with GRP78 To uncover the molecular mechanisms whereby OTUD3 promoted tumorigenicity of lung cancer , mass spectrometry analysis was exerted to discover the OTUD3 interacting partners ( Supplementary Data 2 ) ."
OTUD3 affects tumorigenic LLC cells lung
| 1
OTUD3 activates tumorigenic LLC cells lung. 1 / 1
| 1

eidos
"The results showed that deficiency of OTUD3 suppressed the tumorigenic ability of LLC cells in the lung ( Supplementary Fig. 8a-d ) , and overexpression of OTUD3 enhanced the tumorigenic ability of LLC cells in the lung ( Supplementary Fig. 8e-h ) ."
OTUD3 affects tumorigenesis tumor cells cells microenvironment
| 1
OTUD3 activates tumorigenesis tumor cells cells microenvironment. 1 / 1
| 1

eidos
"What is noteworthy is that OTUD3 promotes tumorigenesis both in tumor cells and in non-tumor cells within the microenvironment ( for example , tumor stroma cell ) ."
OTUD3 affects tumorigenesis lung adenocarcinoma
| 1
OTUD3 activates tumorigenesis lung adenocarcinoma. 1 / 1
| 1

eidos
"Mechanistically , OTUD3 promotes tumorigenesis of the lung adenocarcinoma through deubiquitylating and stabilizing GRP78 ."
OTUD3 affects tumor growth
| 1
OTUD3 inhibits tumor growth. 1 / 1
| 1

eidos
"Secondly , although OTUD3 can inhibit tumor growth and metastasis by stabilizing PTEN in breast cancer , hepatocellular cancer , colon cancer , and cervical cancer , loss of OTUD3 suppressed the tumorigenesis of lung cancer in vitro and in vivo ."
OTUD3 affects sensitivity BC cells apoptosis induced chemotherapy drugs
| 1
OTUD3 activates sensitivity BC cells apoptosis induced chemotherapy drugs. 1 / 1
| 1

eidos
"OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs ."
OTUD3 affects polyubiquitin
| 1
OTUD3 binds PTEN and polyubiquitin. 1 / 1
| 1

sparser
"For example, stabilization of NF-κB/RelA by USP48 [ xref ], stabilization of MCL1 by USP9X [ xref ], and stabilization of PTEN by OTUD3 [ xref ] are associated with the cleavage of K48-linked polyubiquitin from the substrate."
OTUD3 affects migration HCT116 HepG2 HeLa cells folds
| 1
OTUD3 inhibits migration HCT116 HepG2 HeLa cells folds. 1 / 1
| 1

eidos
"Stable depletion of OTUD3 enhanced the migration ability of HCT116 , HepG2 , and HeLa cells to about three folds ( Fig. 3e ) ."

reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
OTUD3 affects lung cancer
| 1
| 1

eidos
"OTUD3 maintained GRP78 stability , leading to lung cancer cell growth and tumorigenesis in vitro and in vivo , even though the precise mechanisms that OTUD3 plays opposite role in different cancers and elevate expression in lung cancer still need further investigation ."

reach
"These findings demonstrate that OTUD3 limits RNA virus-triggered innate immunity but promotes DNA virus-triggered innate immunity."
| 1

reach
"Acetylation Dependent Deubiquitinase OTUD3 Controls MAVS Activation in Innate Antiviral Immunity."
OTUD3 affects half-life GRP78 protein
| 1
OTUD3 activates half-life GRP78 protein. 1 / 1
| 1

eidos
"Notably , overexpression of OTUD3 led to a prolonged half-life of endogenous GRP78 protein ( Fig. 6e ) , whereas depletion of OTUD3 resulted in a shortened half-life of GRP78 protein ( Fig. 6f ) ."
OTUD3 affects gJ
| 1
OTUD3 leads to the deubiquitination of gJ. 1 / 1
| 1

reach
"However, OTUD3 expression reduced uS5 ubiquitylation, albeit to a lesser extent than UPS21 expression, and had no impact on HTN or DTT-induced uS3 ubiquitylation (Figure 7B)."
OTUD3 affects downstream activation IFN signaling
| 1
OTUD3 inhibits downstream activation IFN signaling. 1 / 1
| 1

eidos
"OTU Deubiquitinase 3 ( OTUD3 ) was shown to remove K63-linked ubiquitin chains from MAVS , thereby suppressing MAVS aggregation and downstream activation of type I IFN signaling [ 95 ] ."
OTUD3 affects development mammary tumor mice
| 1
OTUD3 inhibits development mammary tumor mice. 1 / 1
| 1

eidos
"As expected , deficiency of OTUD3 accelerated the development of mammary tumor in MMTV-PyMT transgenic mice , which was consistent with our previous conclusion in OTUD3 transgenic mice ."
OTUD3 affects development lung cancer
| 1
OTUD3 activates development lung cancer. 1 / 1
| 1

eidos
"OTUD3 plays an oncogenic role in lung cancer cells and promotes the development of lung cancer by directly interacting with GRP78 , where OTUD3 deubiquitylates GRP78 and maintains GRP78 stability in vitro and in vivo ."
OTUD3 affects chains
| 1
OTUD3 binds chains. 1 / 1
| 1

reach
"Kinetic studies using di‐Ub substrate probes (di‐Ub‐AMC) suggested that the selectivity of OTUD2 for longer K11‐linked chains is driven by affinity (lower KM), while for OTUD3, it appears to be driven by vmax, hinting that binding of K11 chains to OTUD3 may optimally reorganize the active site for catalysis."
OTUD3 affects cell growth
| 1
| 1

eidos
"Compared with the control cells , OTUD3 depletion suppressed cell growth and migration ( Fig. 4a , d and supplementary Fig. 4a , c ) ."
OTUD3 affects cell growth migration
| 1
OTUD3 activates cell growth migration. 1 / 1
| 1

eidos
"Knockdown of OTUD3 results in a decrease in the level of GRP78 protein , suppression of cell growth and migration , and tumorigenesis in lung cancer ."
OTUD3 affects cGAS
| 1
OTUD3 binds cGAS. 1 / 1
| 1

sparser
"Meanwhile, OTUD3 associates with cGAS and targets at Lys279 to deubiquitinate K48-linked ubiquitination, resulting in the enhancement of cGAS protein stability and DNA-binding ability."
OTUD3 affects ZNF598-mediated ubiquitylation event
| 1
OTUD3 activates ZNF598-mediated ubiquitylation event. 1 / 1
| 1

eidos
"Recently , it was shown that the ZNF598-mediated ubiquitylation event can be reversed by USP21 and OTUD3 , probably to avoid the degradation of the 40S subunit , allowing its recycling in further translation rounds [ 98 ] ."
OTUD3 affects ZFP36
| 1
| 1

sparser
"OTUD3 directly interacts with ZFP36 ring finger protein (ZFP36) and stabilizes it by inhibiting FBXW7-mediated K48-linked polyubiquitination."
OTUD3 affects YOD1
| 1
YOD1 binds OTUD3 and K11. 1 / 1
| 1

sparser
"Highlights d Protease-resistant diUb probes bind to DUB S1-S2 sites and react at the proximal end d First kinetic assay showing proximal end cleavage by DUBs using diUb-based substrates d OTUD3 binds K11-linked diUb and OTUD2 binds K11-and K33-linked diUb in S1-S2 pockets d Kinetics suggest different mechanisms for polyUb cleavage by OTUD2 and OTUD3 SUMMARY Ubiquitin chains are important post-translational modifications that control a large number of cellular processes."
OTUD3 affects VEGFC
| 1
OTUD3 inhibits VEGFC. 1 / 1
| 1

reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
OTUD3 affects VEGF-C mRNA decay
| 1
OTUD3 activates VEGF-C mRNA decay. 1 / 1
| 1

eidos
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer ."
OTUD3 affects USP11, and USP13
| 1
| 1

sparser
"PTEN and DUBs were readily co-immunoprecipitated with each other; however, USP11, USP13, and OTUD3 were not associated with each other (Supplementary Fig.  xref )."
OTUD3 affects TRIM25
1 |
1 |

No evidence text available
OTUD3 affects TPT1
| 1
OTUD3 activates TPT1. 1 / 1
| 1

reach
"Deubiquitylase OTUD3 Mediates Endoplasmic Reticulum Stress through Regulating Fortilin Stability to Restrain Dopaminergic Neurons Apoptosis."
OTUD3 affects STUB1
| 1
| 1

reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
OTUD3 affects S1-S1 0
| 1
OTUD3 binds S1-S1 0. 1 / 1
| 1

reach
"The slower kinetics for K11-linked diUb likely arises from loss of the S2 site contribution but could also be due to alternating binding of K11 diUb to sites on OTUD3, where the diUb can bind either productively to S1-S1 0 or non-productively to S1-S2 sites."
OTUD3 affects RRub
| 1
OTUD3 deubiquitinates RRub on S40. 1 / 1
| 1

reach
"OTUD3 and USP21 deubiquitylate 40S ribosomal proteins following RRub induction."
OTUD3 affects RRub ligases
| 1
OTUD3 inhibits RRub ligases. 1 / 1
| 1

reach
"First, USP21 and OTUD3 may limit the activity of ZNF598 and other RRub ligases through direct antagonism to prevent spurious RRub."
| 1

reach
"Deubiquitylase OTUD3 prevents Parkinson's disease through stabilizing iron regulatory protein 2."
OTUD3 affects PTEN, and polyubiquitin
| 1
OTUD3 binds PTEN and polyubiquitin. 1 / 1
| 1

sparser
"For example, stabilization of NF-κB/RelA by USP48 [ xref ], stabilization of MCL1 by USP9X [ xref ], and stabilization of PTEN by OTUD3 [ xref ] are associated with the cleavage of K48-linked polyubiquitin from the substrate."
OTUD3 affects PTEN, and USP13
| 1
USP13 binds OTUD3 and PTEN. 1 / 1
| 1

sparser
"USP7, a highly expressed DUB in prostate cancer and progressive multifocal leukoencephalopathy (PML), plays a direct role in PTEN deubiquitination and regulates its localization rather than protein stability. xref In addition, USP13 and OTUD3 can interact with PTEN and remove its polyubiquitin chain."
OTUD3 affects OTUD7A
| 1
| 1

reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
OTUD3 affects OTUD6B
| 1
| 1

reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
OTUD3 affects OTUD4
| 1
| 1

reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
OTUD3 affects OTUD3
| 1
OTUD3 inhibits OTUD3. 1 / 1
| 1

reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
OTUD3 affects OTUB1
| 1
| 1

sparser
"Such activity may exist for example in OTUD3, which may bind via its OTU domain to K6 linkages that are extended by a K11 linkage on the distal Ub."
OTUD3 affects MYC
| 1
| 1

sparser
"To determine whether the OTUD3-TP53 interaction was direct, we generated and purified recombinant Myc-OTUD3, Myc-D1 and Myc-D2."

reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
OTUD3 affects Leukemia
| 1
| 1

reach
"These results suggested that OTUD3 may promote tumorigenesis in leukemia."
OTUD3 affects KRAS
| 1
OTUD3 activates KRAS. 1 / 1
| 1

reach
"Our Grp78 mouse model results directly support a recent study showing that in vivo deletion of the deubiquitylase OTUD3 slowed down Kras -driven LUAD initiation and progression and markedly increased survival in mice via destabilization of GRP78 (27)."
OTUD3 affects K63
| 1
DDX58 binds OTUD3 and K63. 1 / 1
| 1

reach
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
OTUD3 affects K11
| 1
YOD1 binds OTUD3 and K11. 1 / 1
| 1

sparser
"Highlights d Protease-resistant diUb probes bind to DUB S1-S2 sites and react at the proximal end d First kinetic assay showing proximal end cleavage by DUBs using diUb-based substrates d OTUD3 binds K11-linked diUb and OTUD2 binds K11-and K33-linked diUb in S1-S2 pockets d Kinetics suggest different mechanisms for polyUb cleavage by OTUD2 and OTUD3 SUMMARY Ubiquitin chains are important post-translational modifications that control a large number of cellular processes."

eidos
"Depletion of OTUD3 results in a disorder of iron metabolism ."
OTUD3 affects Interferon
| 1
| 1

reach
"As an acetylation-dependent deubiquitinase, OTUD3 can restrict IFN signaling by directly hydrolyzing the K63-linked poly-ubiquitinated MAVS at K129 residue (Zhang et al., 2020c)."
OTUD3 affects IFN-I signaling activation
| 1
OTUD3 inhibits IFN-I signaling activation. 1 / 1
| 1

eidos
"For example , OTUD3 removes K63-linked ubiquitin chains from MAVS and thereby inhibits MAVS aggregation and IFN-I signaling activation ( 65 ) ."
OTUD3 affects IFIH1
| 1
| 1

sparser
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
OTUD3 affects GST
| 1
| 1

sparser
"Moreover, purified GST-OTUD3 protein, but not the GST alone, was able to interact with His-GRP78 under cell-free conditions (Fig.  xref ), suggesting a direct interaction between GRP78 and OTUD3."
OTUD3 affects GRP78 ubiquitylation
| 1
OTUD3 inhibits GRP78 ubiquitylation. 1 / 1
| 1

eidos
"Conversely , knockdown of OTUD3 increased GRP78 ubiquitylation ( Fig. 6i ) and this effect was reversed by introduction of shRNA-resistant OTUD3 ( Fig. 6j ) ."
OTUD3 affects GRP78 lung cancer cells
| 1
OTUD3 activates GRP78 lung cancer cells. 1 / 1
| 1

eidos
"Knockdown of CHIP stabilizes OTUD3 which leads to elevated GRP78 levels in lung cancer cells ."
OTUD3 affects FLI1
| 1
OTUD3 deubiquitinates FLI1. 1 / 1
| 1

reach
"Consistently, both OTUD3 and OTUD7A could deubiquitinate EWS–FLI1 in cells (Figure 3C and Figure S8D,E (Supporting Information))."
OTUD3 affects Clone Cells
| 1
| 1

eidos
"OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs ."
OTUD3 affects ChFP
| 1
OTUD3 activates ChFP. 1 / 1
| 1

reach
"USP21 or OTUD3 overexpression in either eS10-KI or uS10-KI cells resulted in a further enhancement of the ChFP:GFP ratio above the respective transfection controls (Figure 4C,D)."
OTUD3 affects CS
| 1
OTUD3 binds CS. 1 / 1
| 1

sparser
"The only instance where there is even a hint of dominant-negative effects is eS10 ubiquitination with OTUD3-CS overexpression (Figure 5D)."
OTUD3 affects C4B_2
| 1
OTUD3 activates C4B_2. 1 / 1
| 1

reach
"Association analysis of genome-wide genetic variants identified dozens of genetic loci associated with CH mutations, including a candidate SNP rs2298110, which may promote CH by increasing expression of a potential leukemia promoter gene OTUD3."
OTUB1 affects OTUD3
| 1
| 1

sparser
"Such activity may exist for example in OTUD3, which may bind via its OTU domain to K6 linkages that are extended by a K11 linkage on the distal Ub."
Mice affects OTUD3
| 1
Mice increases the amount of OTUD3. 1 / 1
| 1

reach
"Lung tissues of BPD mice had downregulated miR-34c-5p expression and upregulated OTUD3 and PTEN expression."
MYC affects OTUD3
| 1
| 1

sparser
"To determine whether the OTUD3-TP53 interaction was direct, we generated and purified recombinant Myc-OTUD3, Myc-D1 and Myc-D2."
MAX affects OTUD3
| 1
MAX activates OTUD3. 1 / 1
| 1

reach
"For OTUD2, the main determinant for S1-S2 site specificity appears to be affinity, whereas for OTUD3 specificity appears to be driven by an increase in V max of the reaction."
Lung Injury affects OTUD3
| 1
| 1

reach
"BMSC-EVs-miR-34c-5p alleviated lung injury and inflammation in hyperoxia-induced BPD by blocking the OTUD3/PTEN axis."
K63 affects OTUD3
| 1
DDX58 binds OTUD3 and K63. 1 / 1
| 1

reach
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
K11 affects YOD1
| 1
YOD1 binds OTUD3 and K11. 1 / 1
| 1

sparser
"Highlights d Protease-resistant diUb probes bind to DUB S1-S2 sites and react at the proximal end d First kinetic assay showing proximal end cleavage by DUBs using diUb-based substrates d OTUD3 binds K11-linked diUb and OTUD2 binds K11-and K33-linked diUb in S1-S2 pockets d Kinetics suggest different mechanisms for polyUb cleavage by OTUD2 and OTUD3 SUMMARY Ubiquitin chains are important post-translational modifications that control a large number of cellular processes."
IFIH1 affects OTUD3
| 1
| 1

sparser
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
Hyperoxia affects OTUD3
| 1
| 1

reach
"BMSC-EVs-miR-34c-5p alleviated lung injury and inflammation in hyperoxia-induced BPD by blocking the OTUD3/PTEN axis."
GST affects OTUD3
| 1
| 1

sparser
"Moreover, purified GST-OTUD3 protein, but not the GST alone, was able to interact with His-GRP78 under cell-free conditions (Fig.  xref ), suggesting a direct interaction between GRP78 and OTUD3."
GSK-J4 affects OTUD3
1 |
GSK-J4 increases the amount of OTUD3. 1 / 1
1 |

No evidence text available
ERN1 affects OTUD3
| 1
ERN1 activates OTUD3. 1 / 1
| 1

reach
"The ratio of p-IRE1α/IRE1α, and the expression of X-box binding protein 1-spliced (XBP1s) were remarkably increased after OTUD3 knockdown, which was inhibited by IRE1α inhibitor STF-083010 treatment."
DDX58 affects K63, and OTUD3
| 1
DDX58 binds OTUD3 and K63. 1 / 1
| 1

reach
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
DDX58 affects IFIH1, and OTUD3
| 1
| 1

sparser
"OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination."
CS affects OTUD3
| 1
OTUD3 binds CS. 1 / 1
| 1

sparser
"The only instance where there is even a hint of dominant-negative effects is eS10 ubiquitination with OTUD3-CS overexpression (Figure 5D)."
BMSC-EVs-miR-34c-5p affects OTUD3
| 1
BMSC-EVs-miR-34c-5p activates OTUD3. 1 / 1
| 1

reach
"BMSC-EVs-miR-34c-5p alleviated lung injury and inflammation in hyperoxia-induced BPD by blocking the OTUD3/PTEN axis."
6-propyl-2-thiouracil decreases the amount of OTUD3. 1 / 1
1 |

No evidence text available
1 |

No evidence text available
17alpha-ethynylestradiol increases the amount of OTUD3. 1 / 1
1 |

No evidence text available